TBD Meeting (2880-23)

Patients with a large cerebral infarction have better functional recovery when they receive endovascular therapy early on in addition to usual medical management, a new study shows.

The trial was stopped early because a planned interim analysis showed efficacy of endovascular therapy in this patient population.

Among patients in China with acute ischemic stroke and a large cerebral infarction, treatment with endovascular therapy within 24 hours after stroke onset “resulted in a better functional outcome at 3 months than medical management alone,” lead author Xiaochuan Huo, MD, PhD, associate chief physician, interventional neurology department, Beijing Tiantan Hospital, Capital Medical University, told this news organization.

“This trial added important evidence for the benefits of endovascular therapy,” Dr. Huo added.

The findings were presented at the International Stroke Conference and were published online in The New England Journal of Medicine. The conference was presented by the American Stroke Association, a division of the American Heart Association.

Will change practice

Commenting on the results, Tudor G. Jovin, MD, professor and chair, department of neurology, Cooper Medical School of Rowan University, Camden, N.J., said he has “little doubt” this study will change practice.

Despite previous studies showing signals of benefit from thrombectomy for patients with large-core infarcts, and some even finding a large treatment effect, “somehow the world didn’t register this,” said Dr. Jovin.

“The stroke community was perhaps reluctant to accept these signals that were there in plain sight because we have been primed for such a long time that reperfusing large infarcts was, if not detrimental, not beneficial.”

But this study, along with another study showing similar results, SELECT 2, which was also presented at this meeting and was published in the same issue of NEJM, provide “overwhelming proof” and “have finally made the community aware,” said Dr. Jovin. “This is sort of a wake-up call to say, ‘Hey, this is real; patients with large infarcts also benefit from thrombectomy.’ “

This new research suggests it’s not necessary to learn the infarct size, at least in the early time window, and doing so just wastes precious time, added Dr. Jovin.

The impact of thrombectomy on patients with “super large infarcts” is still not clear, although these are “extremely rare” in the early time window, perhaps representing only about 1% of patients, said Dr. Jovin.

The increased rate of hemorrhages in study patients receiving thrombectomy “is the price you pay” for the benefits, he said. He noted that this is not any different from the situation with tissue plasminogen activator (tPA), which is routinely used because the benefits far outweigh the risks.
 

ANGEL-ASPECT

As patients with large infarctions are generally excluded from studies of thrombectomy, it’s been unclear whether they benefit from this therapy, the researchers noted.

The multicenter Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core (ANGEL-ASPECT) trial included 455 adult patients (median age, 68 years; 38.7% women) who had a large infarct core caused by acute large-vessel occlusion in the anterior circulation (Alberta Stroke Program Early CT Score [ASPECTS] 3-5 without core volume limitations or ASPECTS 0–2 with core volume between 70 and 100 mL).

Study participants had to have a score of 6-30 on the National Institutes of Health Stroke Scale (NIHSS) and a retrospectively determined prestroke score of 0 or 1 on the Modified Rankin Scale (mRS).

The median baseline NIHSS score of study patients was 16, the median ASPECTS was 3, and the median infarct-core volume was 62 mL.

Researchers randomly assigned patients to undergo either medical management alone or medical management as well as endovascular therapy. Medical management included intravenous (IV) thrombolysis for those who were eligible.

IV thrombolysis was administered before thrombectomy for about 28% of patients in each group. Some 78.7% of all patients arrived at the hospital outside the typical 4.5-hour window and were ineligible for thrombolysis.

A greater percentage of patients in the endovascular therapy group was receiving antihypertensive medications (83.0%) than in the medical management alone group (54.0%). About 20% of patients in each group were taking an anticoagulant medication.

When the trial was halted, outcome data were available for 336 patients. An additional 120 patients had undergone randomization, and 455 had completed 90 days of follow-up.
 

Better functional outcome

The primary outcome was the score on the mRS at 90 days. Results showed a shift in the distribution of scores on the mRS at 90 days toward better outcomes favoring endovascular therapy over medical management alone (generalized odds ratio, 1.37; 95% confidence interval [CI], 1.11-1.69; P = .004).

The efficacy of endovascular therapy with respect to the primary outcome was similar across predefined subgroups and across all trial sites. However, the trial was not powered to allow definite conclusions based on the results of subgroup analyses.

Although patients with an ASPECT score of 0-2 (indicating very large infarct cores) are considered unlikely to benefit from endovascular treatment, the researchers did find some signals of gain for these patients.

“Although no conclusions can be drawn because the trial was not powered for this analysis and the confidence interval for the odds ratio between the trial groups included 1, there may have been a benefit with endovascular therapy in this subgroup,” the authors wrote. “More trials are warranted to determine if this benefit is valid.”

As for secondary outcomes, the percentage of patients with a score of 0-2 on the mRS at 90 days was 30.0% in the endovascular therapy group and 11.6% in the medical management group (relative risk [RR], 2.62; 95% CI, 1.69-4.06).

The percentage of patients with a score of 0-3 on the mRS at 90 days was 47.0% in the endovascular therapy group and 33.3% in the medical management group (RR, 1.50; 95% CI, 1.17-1.91).

The primary safety outcome was symptomatic intracranial hemorrhage within 48 hours, which occurred in 6.1% of the endovascular therapy group, compared to 2.7% in the medical management group (RR, 2.07; 95% CI, 0.79-5.41; P = .12)

Mortality within 90 days was 21.7% in the endovascular therapy group and 20.0% in the medical management group. Other serious adverse events occurred in 40.0% in the endovascular therapy group and 38.2% in the medical management group (P = .70).

The percentage of patients receiving IV thrombolysis was relatively low, which may have affected outcomes in the medical management group. Another potential limitation was that urokinase rather than alteplase, which is probably more effective, was used for thrombolysis in a small percentage of patients.

Further, the study did not include patients older than 80 years or those with an ASPECT value greater than 5 and infarct core volume of 70-100 mL, and it included only Chinese patients, so the results may not be generalizable, the researchers noted.

These findings will likely change clinical practice, said Dr. Huo, who noted that the current guideline doesn’t provide “a high-level recommendation” for [endovascular therapy] in patients with a low ASPECT score.

“These new results will change the guideline” to suggest endovascular therapy for large-core patients, he said.
 

Welcome news

An accompanying editorial by Pierre Fayad, MD, department of neurological sciences, division of vascular neurology and stroke, University of Nebraska Medical Center, Omaha, welcomed results from this and other recent related studies.

From these new results, “it is reasonable to suggest that endovascular thrombectomy be offered to patients with large strokes” if they arrive in a timely fashion at a center capable of performing the procedure and have an ASPECT value of 3-5 or an ischemic-core volume of 50 mL or greater, he wrote.

“The improved chance of independent walking and the ability to perform other daily activities in patients with the most severe strokes is welcome news for patients and for the field of stroke treatment.”

The study received funding from Covidien Healthcare International Trading (Shanghai), Johnson & Johnson MedTech, Genesis MedTech (Shanghai), and Shanghai HeartCare Medical Technology. Dr. Huo and Dr. Jovin report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients with a large cerebral infarction have better functional recovery when they receive endovascular therapy early on in addition to usual medical management, a new study shows.

The trial was stopped early because a planned interim analysis showed efficacy of endovascular therapy in this patient population.

Among patients in China with acute ischemic stroke and a large cerebral infarction, treatment with endovascular therapy within 24 hours after stroke onset “resulted in a better functional outcome at 3 months than medical management alone,” lead author Xiaochuan Huo, MD, PhD, associate chief physician, interventional neurology department, Beijing Tiantan Hospital, Capital Medical University, told this news organization.

“This trial added important evidence for the benefits of endovascular therapy,” Dr. Huo added.

The findings were presented at the International Stroke Conference and were published online in The New England Journal of Medicine. The conference was presented by the American Stroke Association, a division of the American Heart Association.

Will change practice

Commenting on the results, Tudor G. Jovin, MD, professor and chair, department of neurology, Cooper Medical School of Rowan University, Camden, N.J., said he has “little doubt” this study will change practice.

Despite previous studies showing signals of benefit from thrombectomy for patients with large-core infarcts, and some even finding a large treatment effect, “somehow the world didn’t register this,” said Dr. Jovin.

“The stroke community was perhaps reluctant to accept these signals that were there in plain sight because we have been primed for such a long time that reperfusing large infarcts was, if not detrimental, not beneficial.”

But this study, along with another study showing similar results, SELECT 2, which was also presented at this meeting and was published in the same issue of NEJM, provide “overwhelming proof” and “have finally made the community aware,” said Dr. Jovin. “This is sort of a wake-up call to say, ‘Hey, this is real; patients with large infarcts also benefit from thrombectomy.’ “

This new research suggests it’s not necessary to learn the infarct size, at least in the early time window, and doing so just wastes precious time, added Dr. Jovin.

The impact of thrombectomy on patients with “super large infarcts” is still not clear, although these are “extremely rare” in the early time window, perhaps representing only about 1% of patients, said Dr. Jovin.

The increased rate of hemorrhages in study patients receiving thrombectomy “is the price you pay” for the benefits, he said. He noted that this is not any different from the situation with tissue plasminogen activator (tPA), which is routinely used because the benefits far outweigh the risks.
 

ANGEL-ASPECT

As patients with large infarctions are generally excluded from studies of thrombectomy, it’s been unclear whether they benefit from this therapy, the researchers noted.

The multicenter Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core (ANGEL-ASPECT) trial included 455 adult patients (median age, 68 years; 38.7% women) who had a large infarct core caused by acute large-vessel occlusion in the anterior circulation (Alberta Stroke Program Early CT Score [ASPECTS] 3-5 without core volume limitations or ASPECTS 0–2 with core volume between 70 and 100 mL).

Study participants had to have a score of 6-30 on the National Institutes of Health Stroke Scale (NIHSS) and a retrospectively determined prestroke score of 0 or 1 on the Modified Rankin Scale (mRS).

The median baseline NIHSS score of study patients was 16, the median ASPECTS was 3, and the median infarct-core volume was 62 mL.

Researchers randomly assigned patients to undergo either medical management alone or medical management as well as endovascular therapy. Medical management included intravenous (IV) thrombolysis for those who were eligible.

IV thrombolysis was administered before thrombectomy for about 28% of patients in each group. Some 78.7% of all patients arrived at the hospital outside the typical 4.5-hour window and were ineligible for thrombolysis.

A greater percentage of patients in the endovascular therapy group was receiving antihypertensive medications (83.0%) than in the medical management alone group (54.0%). About 20% of patients in each group were taking an anticoagulant medication.

When the trial was halted, outcome data were available for 336 patients. An additional 120 patients had undergone randomization, and 455 had completed 90 days of follow-up.
 

Better functional outcome

The primary outcome was the score on the mRS at 90 days. Results showed a shift in the distribution of scores on the mRS at 90 days toward better outcomes favoring endovascular therapy over medical management alone (generalized odds ratio, 1.37; 95% confidence interval [CI], 1.11-1.69; P = .004).

The efficacy of endovascular therapy with respect to the primary outcome was similar across predefined subgroups and across all trial sites. However, the trial was not powered to allow definite conclusions based on the results of subgroup analyses.

Although patients with an ASPECT score of 0-2 (indicating very large infarct cores) are considered unlikely to benefit from endovascular treatment, the researchers did find some signals of gain for these patients.

“Although no conclusions can be drawn because the trial was not powered for this analysis and the confidence interval for the odds ratio between the trial groups included 1, there may have been a benefit with endovascular therapy in this subgroup,” the authors wrote. “More trials are warranted to determine if this benefit is valid.”

As for secondary outcomes, the percentage of patients with a score of 0-2 on the mRS at 90 days was 30.0% in the endovascular therapy group and 11.6% in the medical management group (relative risk [RR], 2.62; 95% CI, 1.69-4.06).

The percentage of patients with a score of 0-3 on the mRS at 90 days was 47.0% in the endovascular therapy group and 33.3% in the medical management group (RR, 1.50; 95% CI, 1.17-1.91).

The primary safety outcome was symptomatic intracranial hemorrhage within 48 hours, which occurred in 6.1% of the endovascular therapy group, compared to 2.7% in the medical management group (RR, 2.07; 95% CI, 0.79-5.41; P = .12)

Mortality within 90 days was 21.7% in the endovascular therapy group and 20.0% in the medical management group. Other serious adverse events occurred in 40.0% in the endovascular therapy group and 38.2% in the medical management group (P = .70).

The percentage of patients receiving IV thrombolysis was relatively low, which may have affected outcomes in the medical management group. Another potential limitation was that urokinase rather than alteplase, which is probably more effective, was used for thrombolysis in a small percentage of patients.

Further, the study did not include patients older than 80 years or those with an ASPECT value greater than 5 and infarct core volume of 70-100 mL, and it included only Chinese patients, so the results may not be generalizable, the researchers noted.

These findings will likely change clinical practice, said Dr. Huo, who noted that the current guideline doesn’t provide “a high-level recommendation” for [endovascular therapy] in patients with a low ASPECT score.

“These new results will change the guideline” to suggest endovascular therapy for large-core patients, he said.
 

Welcome news

An accompanying editorial by Pierre Fayad, MD, department of neurological sciences, division of vascular neurology and stroke, University of Nebraska Medical Center, Omaha, welcomed results from this and other recent related studies.

From these new results, “it is reasonable to suggest that endovascular thrombectomy be offered to patients with large strokes” if they arrive in a timely fashion at a center capable of performing the procedure and have an ASPECT value of 3-5 or an ischemic-core volume of 50 mL or greater, he wrote.

“The improved chance of independent walking and the ability to perform other daily activities in patients with the most severe strokes is welcome news for patients and for the field of stroke treatment.”

The study received funding from Covidien Healthcare International Trading (Shanghai), Johnson & Johnson MedTech, Genesis MedTech (Shanghai), and Shanghai HeartCare Medical Technology. Dr. Huo and Dr. Jovin report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients with a large cerebral infarction have better functional recovery when they receive endovascular therapy early on in addition to usual medical management, a new study shows.

The trial was stopped early because a planned interim analysis showed efficacy of endovascular therapy in this patient population.

Among patients in China with acute ischemic stroke and a large cerebral infarction, treatment with endovascular therapy within 24 hours after stroke onset “resulted in a better functional outcome at 3 months than medical management alone,” lead author Xiaochuan Huo, MD, PhD, associate chief physician, interventional neurology department, Beijing Tiantan Hospital, Capital Medical University, told this news organization.

“This trial added important evidence for the benefits of endovascular therapy,” Dr. Huo added.

The findings were presented at the International Stroke Conference and were published online in The New England Journal of Medicine. The conference was presented by the American Stroke Association, a division of the American Heart Association.

Will change practice

Commenting on the results, Tudor G. Jovin, MD, professor and chair, department of neurology, Cooper Medical School of Rowan University, Camden, N.J., said he has “little doubt” this study will change practice.

Despite previous studies showing signals of benefit from thrombectomy for patients with large-core infarcts, and some even finding a large treatment effect, “somehow the world didn’t register this,” said Dr. Jovin.

“The stroke community was perhaps reluctant to accept these signals that were there in plain sight because we have been primed for such a long time that reperfusing large infarcts was, if not detrimental, not beneficial.”

But this study, along with another study showing similar results, SELECT 2, which was also presented at this meeting and was published in the same issue of NEJM, provide “overwhelming proof” and “have finally made the community aware,” said Dr. Jovin. “This is sort of a wake-up call to say, ‘Hey, this is real; patients with large infarcts also benefit from thrombectomy.’ “

This new research suggests it’s not necessary to learn the infarct size, at least in the early time window, and doing so just wastes precious time, added Dr. Jovin.

The impact of thrombectomy on patients with “super large infarcts” is still not clear, although these are “extremely rare” in the early time window, perhaps representing only about 1% of patients, said Dr. Jovin.

The increased rate of hemorrhages in study patients receiving thrombectomy “is the price you pay” for the benefits, he said. He noted that this is not any different from the situation with tissue plasminogen activator (tPA), which is routinely used because the benefits far outweigh the risks.
 

ANGEL-ASPECT

As patients with large infarctions are generally excluded from studies of thrombectomy, it’s been unclear whether they benefit from this therapy, the researchers noted.

The multicenter Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core (ANGEL-ASPECT) trial included 455 adult patients (median age, 68 years; 38.7% women) who had a large infarct core caused by acute large-vessel occlusion in the anterior circulation (Alberta Stroke Program Early CT Score [ASPECTS] 3-5 without core volume limitations or ASPECTS 0–2 with core volume between 70 and 100 mL).

Study participants had to have a score of 6-30 on the National Institutes of Health Stroke Scale (NIHSS) and a retrospectively determined prestroke score of 0 or 1 on the Modified Rankin Scale (mRS).

The median baseline NIHSS score of study patients was 16, the median ASPECTS was 3, and the median infarct-core volume was 62 mL.

Researchers randomly assigned patients to undergo either medical management alone or medical management as well as endovascular therapy. Medical management included intravenous (IV) thrombolysis for those who were eligible.

IV thrombolysis was administered before thrombectomy for about 28% of patients in each group. Some 78.7% of all patients arrived at the hospital outside the typical 4.5-hour window and were ineligible for thrombolysis.

A greater percentage of patients in the endovascular therapy group was receiving antihypertensive medications (83.0%) than in the medical management alone group (54.0%). About 20% of patients in each group were taking an anticoagulant medication.

When the trial was halted, outcome data were available for 336 patients. An additional 120 patients had undergone randomization, and 455 had completed 90 days of follow-up.
 

Better functional outcome

The primary outcome was the score on the mRS at 90 days. Results showed a shift in the distribution of scores on the mRS at 90 days toward better outcomes favoring endovascular therapy over medical management alone (generalized odds ratio, 1.37; 95% confidence interval [CI], 1.11-1.69; P = .004).

The efficacy of endovascular therapy with respect to the primary outcome was similar across predefined subgroups and across all trial sites. However, the trial was not powered to allow definite conclusions based on the results of subgroup analyses.

Although patients with an ASPECT score of 0-2 (indicating very large infarct cores) are considered unlikely to benefit from endovascular treatment, the researchers did find some signals of gain for these patients.

“Although no conclusions can be drawn because the trial was not powered for this analysis and the confidence interval for the odds ratio between the trial groups included 1, there may have been a benefit with endovascular therapy in this subgroup,” the authors wrote. “More trials are warranted to determine if this benefit is valid.”

As for secondary outcomes, the percentage of patients with a score of 0-2 on the mRS at 90 days was 30.0% in the endovascular therapy group and 11.6% in the medical management group (relative risk [RR], 2.62; 95% CI, 1.69-4.06).

The percentage of patients with a score of 0-3 on the mRS at 90 days was 47.0% in the endovascular therapy group and 33.3% in the medical management group (RR, 1.50; 95% CI, 1.17-1.91).

The primary safety outcome was symptomatic intracranial hemorrhage within 48 hours, which occurred in 6.1% of the endovascular therapy group, compared to 2.7% in the medical management group (RR, 2.07; 95% CI, 0.79-5.41; P = .12)

Mortality within 90 days was 21.7% in the endovascular therapy group and 20.0% in the medical management group. Other serious adverse events occurred in 40.0% in the endovascular therapy group and 38.2% in the medical management group (P = .70).

The percentage of patients receiving IV thrombolysis was relatively low, which may have affected outcomes in the medical management group. Another potential limitation was that urokinase rather than alteplase, which is probably more effective, was used for thrombolysis in a small percentage of patients.

Further, the study did not include patients older than 80 years or those with an ASPECT value greater than 5 and infarct core volume of 70-100 mL, and it included only Chinese patients, so the results may not be generalizable, the researchers noted.

These findings will likely change clinical practice, said Dr. Huo, who noted that the current guideline doesn’t provide “a high-level recommendation” for [endovascular therapy] in patients with a low ASPECT score.

“These new results will change the guideline” to suggest endovascular therapy for large-core patients, he said.
 

Welcome news

An accompanying editorial by Pierre Fayad, MD, department of neurological sciences, division of vascular neurology and stroke, University of Nebraska Medical Center, Omaha, welcomed results from this and other recent related studies.

From these new results, “it is reasonable to suggest that endovascular thrombectomy be offered to patients with large strokes” if they arrive in a timely fashion at a center capable of performing the procedure and have an ASPECT value of 3-5 or an ischemic-core volume of 50 mL or greater, he wrote.

“The improved chance of independent walking and the ability to perform other daily activities in patients with the most severe strokes is welcome news for patients and for the field of stroke treatment.”

The study received funding from Covidien Healthcare International Trading (Shanghai), Johnson & Johnson MedTech, Genesis MedTech (Shanghai), and Shanghai HeartCare Medical Technology. Dr. Huo and Dr. Jovin report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In patients with acute ischemic stroke who have not received thrombolysis or thrombectomy, early antihypertensive treatment compared with delayed antihypertensive treatment did not reduce the likelihood of death and major disability at 3 months in the CATIS-2 trial.

The trial was presented by Liping Liu, MD, Beijing Tiantan Hospital, at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

“Antihypertensive treatment can be delayed for at least 7 days following ischemic stroke onset, unless there are severe acute comorbidities that demand emergency blood pressure reduction to prevent serious complications,” Dr. Liu concluded.

But he acknowledged that the optimal BP management strategy in these patients remains uncertain and should be the focus of future research.

Discussing the trial at an ISC 2023 Highlights session, Lauren Sansing, MD, Yale University, New Haven, Conn., and ISC program vice chair, said: “These results seem to support waiting for a week or so before treating blood pressure in these patients.”

But Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., and ISC program chair, countered: “To me, it’s kind of a neutral result, so what I take home from this is that you don’t necessarily have to wait.”

Dr. Jovin continued: “We used to think that it was mandatory not to treat blood pressure early because of the risk of deceasing the perfusion pressure, but this trial suggests the effects are neutral and there is probably as much benefit from lowering blood pressure for other reasons that offsets the potential harm.

“I think these are good data to rely on when we make these kinds of treatment decisions. Personally, I am a bit more aggressive with early blood pressure management and it’s good to see that you don’t get punished for that,” he added.

In his presentation, Dr. Liu explained that increased BP is common in acute stroke and is strongly associated with poor functional outcome and recurrence of ischemic stroke, but the optimal blood pressure management strategy in acute ischemic stroke remains controversial.

In the first CATIS trial (China Antihypertensive Trial in Acute Ischemic Stroke), which compared antihypertensive treatment within 48 hours of stroke onset with no antihypertensive treatment in ischemic stroke patients not receiving thrombolysis, the main results suggested that BP reduction with antihypertensive medications did not reduce the likelihood of death and major disability at 14 days or hospital discharge. But a subgroup analysis found that initiating antihypertensive treatment between 24 and 48 hours of stroke onset showed a beneficial effect on reducing death or major disability.

Current AHA/ASA guidelines suggest that, in patients with BP greater than 220/120 mm Hg who have not received thrombolysis or thrombectomy and have no comorbid conditions requiring urgent antihypertensive treatment, the benefit of initiating or reinitiating antihypertensive treatment within the first 48-72 hours is uncertain, although the guidelines say it might be reasonable to lower BP by around 15% during the first 24 hours after stroke onset, Dr. Liu noted.

The CATIS-2 trial was a multicenter, randomized, open-label, blinded-endpoints trial conducted at 106 centers in China that enrolled 4810 patients within 24-48 hours of onset of acute ischemic stroke who had elevated BP. Patients had not received thrombolytic therapy or mechanical thrombectomy.

Patients were randomly assigned to early antihypertensive therapy (initiated after randomization and aiming for a 10%-20% reduction in systolic BP) or delayed antihypertensive therapy (restarted antihypertensive therapy on day 8 of randomization, aiming for a BP of < 140/90 mm Hg).

The median age of the patients was 64 years, 65% were male, 80% had a history of hypertension, and the median National Institutes of Health Stroke Scale score was 3. Baseline BP averaged 163/92 mm Hg in both groups. The median time from stroke onset to antihypertensive treatment was 1.5 days in the early group and 8.5 days in the delayed group.

BP results showed that, at 24 hours after randomization, mean systolic pressure was reduced by 16.4 mm Hg (9.7%) in the early-treatment group and by 8.6 mm Hg (4.9%) in the delayed-treatment group (difference, –7.8 mm Hg; P < .0001).

At day 7, mean systolic pressure was 139.1 mm Hg in the early-treatment group, compared with 150.9 mm Hg in the delayed-treatment group, with a net difference in systolic BP of –11.9 mm Hg (P < .0001).

The primary outcome was the composite of death and major disability (modified Rankin Scale ≥ 3) at 3 months. This did not differ between the groups, occurring in 12.1% in the early antihypertensive treatment group versus 10.5% in the delayed antihypertensive treatment group (risk ratio, 1.15; P = .08).

There was also no difference in the major secondary outcome of shift in scores of mRS at 3 months, with a common odds ratio of 1.05 (95% confidence interval, 0.95-1.17).

There was no interaction with the composite outcome of death or major disability at 90 days in the prespecified subgroups.

Dr. Liu pointed out several limitations of the study. These included an observed primary outcome rate substantially lower than expected; the BP reduction seen within the first 7 days in the early-treatment group was moderate; and the results of the study cannot be applied to patients treated with thrombolysis or thrombectomy.

Dr. Liu has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In patients with acute ischemic stroke who have not received thrombolysis or thrombectomy, early antihypertensive treatment compared with delayed antihypertensive treatment did not reduce the likelihood of death and major disability at 3 months in the CATIS-2 trial.

The trial was presented by Liping Liu, MD, Beijing Tiantan Hospital, at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

“Antihypertensive treatment can be delayed for at least 7 days following ischemic stroke onset, unless there are severe acute comorbidities that demand emergency blood pressure reduction to prevent serious complications,” Dr. Liu concluded.

But he acknowledged that the optimal BP management strategy in these patients remains uncertain and should be the focus of future research.

Discussing the trial at an ISC 2023 Highlights session, Lauren Sansing, MD, Yale University, New Haven, Conn., and ISC program vice chair, said: “These results seem to support waiting for a week or so before treating blood pressure in these patients.”

But Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., and ISC program chair, countered: “To me, it’s kind of a neutral result, so what I take home from this is that you don’t necessarily have to wait.”

Dr. Jovin continued: “We used to think that it was mandatory not to treat blood pressure early because of the risk of deceasing the perfusion pressure, but this trial suggests the effects are neutral and there is probably as much benefit from lowering blood pressure for other reasons that offsets the potential harm.

“I think these are good data to rely on when we make these kinds of treatment decisions. Personally, I am a bit more aggressive with early blood pressure management and it’s good to see that you don’t get punished for that,” he added.

In his presentation, Dr. Liu explained that increased BP is common in acute stroke and is strongly associated with poor functional outcome and recurrence of ischemic stroke, but the optimal blood pressure management strategy in acute ischemic stroke remains controversial.

In the first CATIS trial (China Antihypertensive Trial in Acute Ischemic Stroke), which compared antihypertensive treatment within 48 hours of stroke onset with no antihypertensive treatment in ischemic stroke patients not receiving thrombolysis, the main results suggested that BP reduction with antihypertensive medications did not reduce the likelihood of death and major disability at 14 days or hospital discharge. But a subgroup analysis found that initiating antihypertensive treatment between 24 and 48 hours of stroke onset showed a beneficial effect on reducing death or major disability.

Current AHA/ASA guidelines suggest that, in patients with BP greater than 220/120 mm Hg who have not received thrombolysis or thrombectomy and have no comorbid conditions requiring urgent antihypertensive treatment, the benefit of initiating or reinitiating antihypertensive treatment within the first 48-72 hours is uncertain, although the guidelines say it might be reasonable to lower BP by around 15% during the first 24 hours after stroke onset, Dr. Liu noted.

The CATIS-2 trial was a multicenter, randomized, open-label, blinded-endpoints trial conducted at 106 centers in China that enrolled 4810 patients within 24-48 hours of onset of acute ischemic stroke who had elevated BP. Patients had not received thrombolytic therapy or mechanical thrombectomy.

Patients were randomly assigned to early antihypertensive therapy (initiated after randomization and aiming for a 10%-20% reduction in systolic BP) or delayed antihypertensive therapy (restarted antihypertensive therapy on day 8 of randomization, aiming for a BP of < 140/90 mm Hg).

The median age of the patients was 64 years, 65% were male, 80% had a history of hypertension, and the median National Institutes of Health Stroke Scale score was 3. Baseline BP averaged 163/92 mm Hg in both groups. The median time from stroke onset to antihypertensive treatment was 1.5 days in the early group and 8.5 days in the delayed group.

BP results showed that, at 24 hours after randomization, mean systolic pressure was reduced by 16.4 mm Hg (9.7%) in the early-treatment group and by 8.6 mm Hg (4.9%) in the delayed-treatment group (difference, –7.8 mm Hg; P < .0001).

At day 7, mean systolic pressure was 139.1 mm Hg in the early-treatment group, compared with 150.9 mm Hg in the delayed-treatment group, with a net difference in systolic BP of –11.9 mm Hg (P < .0001).

The primary outcome was the composite of death and major disability (modified Rankin Scale ≥ 3) at 3 months. This did not differ between the groups, occurring in 12.1% in the early antihypertensive treatment group versus 10.5% in the delayed antihypertensive treatment group (risk ratio, 1.15; P = .08).

There was also no difference in the major secondary outcome of shift in scores of mRS at 3 months, with a common odds ratio of 1.05 (95% confidence interval, 0.95-1.17).

There was no interaction with the composite outcome of death or major disability at 90 days in the prespecified subgroups.

Dr. Liu pointed out several limitations of the study. These included an observed primary outcome rate substantially lower than expected; the BP reduction seen within the first 7 days in the early-treatment group was moderate; and the results of the study cannot be applied to patients treated with thrombolysis or thrombectomy.

Dr. Liu has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In patients with acute ischemic stroke who have not received thrombolysis or thrombectomy, early antihypertensive treatment compared with delayed antihypertensive treatment did not reduce the likelihood of death and major disability at 3 months in the CATIS-2 trial.

The trial was presented by Liping Liu, MD, Beijing Tiantan Hospital, at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

“Antihypertensive treatment can be delayed for at least 7 days following ischemic stroke onset, unless there are severe acute comorbidities that demand emergency blood pressure reduction to prevent serious complications,” Dr. Liu concluded.

But he acknowledged that the optimal BP management strategy in these patients remains uncertain and should be the focus of future research.

Discussing the trial at an ISC 2023 Highlights session, Lauren Sansing, MD, Yale University, New Haven, Conn., and ISC program vice chair, said: “These results seem to support waiting for a week or so before treating blood pressure in these patients.”

But Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., and ISC program chair, countered: “To me, it’s kind of a neutral result, so what I take home from this is that you don’t necessarily have to wait.”

Dr. Jovin continued: “We used to think that it was mandatory not to treat blood pressure early because of the risk of deceasing the perfusion pressure, but this trial suggests the effects are neutral and there is probably as much benefit from lowering blood pressure for other reasons that offsets the potential harm.

“I think these are good data to rely on when we make these kinds of treatment decisions. Personally, I am a bit more aggressive with early blood pressure management and it’s good to see that you don’t get punished for that,” he added.

In his presentation, Dr. Liu explained that increased BP is common in acute stroke and is strongly associated with poor functional outcome and recurrence of ischemic stroke, but the optimal blood pressure management strategy in acute ischemic stroke remains controversial.

In the first CATIS trial (China Antihypertensive Trial in Acute Ischemic Stroke), which compared antihypertensive treatment within 48 hours of stroke onset with no antihypertensive treatment in ischemic stroke patients not receiving thrombolysis, the main results suggested that BP reduction with antihypertensive medications did not reduce the likelihood of death and major disability at 14 days or hospital discharge. But a subgroup analysis found that initiating antihypertensive treatment between 24 and 48 hours of stroke onset showed a beneficial effect on reducing death or major disability.

Current AHA/ASA guidelines suggest that, in patients with BP greater than 220/120 mm Hg who have not received thrombolysis or thrombectomy and have no comorbid conditions requiring urgent antihypertensive treatment, the benefit of initiating or reinitiating antihypertensive treatment within the first 48-72 hours is uncertain, although the guidelines say it might be reasonable to lower BP by around 15% during the first 24 hours after stroke onset, Dr. Liu noted.

The CATIS-2 trial was a multicenter, randomized, open-label, blinded-endpoints trial conducted at 106 centers in China that enrolled 4810 patients within 24-48 hours of onset of acute ischemic stroke who had elevated BP. Patients had not received thrombolytic therapy or mechanical thrombectomy.

Patients were randomly assigned to early antihypertensive therapy (initiated after randomization and aiming for a 10%-20% reduction in systolic BP) or delayed antihypertensive therapy (restarted antihypertensive therapy on day 8 of randomization, aiming for a BP of < 140/90 mm Hg).

The median age of the patients was 64 years, 65% were male, 80% had a history of hypertension, and the median National Institutes of Health Stroke Scale score was 3. Baseline BP averaged 163/92 mm Hg in both groups. The median time from stroke onset to antihypertensive treatment was 1.5 days in the early group and 8.5 days in the delayed group.

BP results showed that, at 24 hours after randomization, mean systolic pressure was reduced by 16.4 mm Hg (9.7%) in the early-treatment group and by 8.6 mm Hg (4.9%) in the delayed-treatment group (difference, –7.8 mm Hg; P < .0001).

At day 7, mean systolic pressure was 139.1 mm Hg in the early-treatment group, compared with 150.9 mm Hg in the delayed-treatment group, with a net difference in systolic BP of –11.9 mm Hg (P < .0001).

The primary outcome was the composite of death and major disability (modified Rankin Scale ≥ 3) at 3 months. This did not differ between the groups, occurring in 12.1% in the early antihypertensive treatment group versus 10.5% in the delayed antihypertensive treatment group (risk ratio, 1.15; P = .08).

There was also no difference in the major secondary outcome of shift in scores of mRS at 3 months, with a common odds ratio of 1.05 (95% confidence interval, 0.95-1.17).

There was no interaction with the composite outcome of death or major disability at 90 days in the prespecified subgroups.

Dr. Liu pointed out several limitations of the study. These included an observed primary outcome rate substantially lower than expected; the BP reduction seen within the first 7 days in the early-treatment group was moderate; and the results of the study cannot be applied to patients treated with thrombolysis or thrombectomy.

Dr. Liu has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Among Chinese patients with minor nondisabling stroke who presented within 4.5 hours of symptom onset, dual antiplatelet treatment was noninferior to thrombolysis with intravenous alteplase with regard to functional outcome at 90 days in the ARAMIS trial.

The trial was presented by Thanh Nguyen, MD, Boston Medical Center, at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

“Given the ease of administration, less intensive monitoring, low cost, and safety profile of dual antiplatelet therapy, the current findings support the use of dual antiplatelet in this population,” Dr. Nguyen concluded.

In a comment on the trial, Pooja Khatri, MD, professor of neurology at the University of Cincinnati, and lead investigator of the previous PRISMS study of tissue plasminogen activator (tPA) or alteplase in mild stroke, said the results reinforced the current recommendations of giving dual antiplatelet therapy but not alteplase to these patients.

Noting that the standard of care is now to give dual antiplatelet therapy to these patients, Dr. Khatri said: “These data reassure that this remains the right way to go.”

She added that her take-home message from the study would be: “Keep giving dual antiplatelet therapy, and we may be doing more harm than good with alteplase in this patient population.”

Introducing her presentation, Dr. Nguyen explained that mild ischemic stroke, defined as having a National Institutes of Health Stroke Scale (NIHSS) score of 5 or less, comprises half of ischemic stroke patients in the United States. But the benefit of thrombolysis in patients with minor ischemic stroke that is not disabling is unknown.

A subgroup analysis of one of the major thrombolysis trials (IST-3) found that a higher proportion of patients with mild ischemic stroke who were treated within 3 hours of symptom onset were alive and independent at 6 months if they had been given thrombolysis (84%), compared to 65% in the control group who received standard medical treatment.

This led to the first randomized trial (PRISMS) dedicated to patients with mild nondisabling stroke, which found that alteplase given within 3 hours of symptom onset did not increase the likelihood of a good functional outcome at 90 days in comparison with single-agent aspirin. The study was unfortunately terminated early for administrative reasons, and no definitive conclusions could be drawn on the basis of these results, Dr. Nguyen reported.

In 2018, the American Heart Association/American Stroke Association guidelines indicated that for patients who present within 3 hours of symptom onset with mild ischemic stroke that was judged to be nondisabling, thrombolysis with intravenous alteplase could be considered, she noted.

In the meantime, dual antiplatelet therapy was shown to be safe and effective in the POINT and CHANCE trials in patients presenting with minor stroke within 12 or 24 hours, and the CHANCE trial also found a benefit in reducing recurrent stroke that was most effective in the first 2 weeks.

The current ARAMIS trial was therefore conducted to evaluate dual antiplatelet therapy in comparison with thrombolysis for patients with acute minor stroke (NIHSS 5 or less) who presented within 4.5 hours of symptom onset and were without clearly disabling deficit.

The trial was conducted in 38 hospitals in China and included 760 patients (median NIHSS score of 2) who were randomly assigned to receive intravenous alteplase at the standard dose of 0.9 mg/kg, followed by guideline-based antiplatelet treatment, or dual antiplatelet therapy (clopidogrel 300 mg plus 100 mg aspirin loading dose followed by 10 to 14 days of aspirin 100 mg and clopidogrel 75 mg).

The trial was designed to assess noninferiority of dual antiplatelet therapy to alteplase with noninferiority margin of –4.5%.

In the modified intention-to-treat analysis, which included 722 patients, the primary outcome (excellent functional outcome, defined as a Modified Rankin Scale score of 0 or 1 at 90 days) occurred in 93.8% of patients in the dual antiplatelet therapy group and in 91.4% of the alteplase group. This gave a difference of 2.4%, which fell within the limits for noninferiority (P = .0002 for noninferiority test).

“Therefore, this was a positive trial,” Dr. Nguyen stated.

About 20% of patients crossed over from the dual antiplatelet group to the thrombolysis group, and about 16% of patients crossed over from the thrombolysis group to the dual antiplatelet group. But a per-protocol and an “as treated” analysis showed results similar to those of the main intention-to-treat analysis.

Secondary outcomes were largely similar between the two groups other than early neurologic deterioration, which was less common in the dual antiplatelet therapy group.

In terms of safety, symptomatic intracranial hemorrhage occurred in 0.3% (1/369) in the dual antiplatelet group and in 0.9% (3/350) in the alteplase group, a nonsignificant difference.

Events of “any bleeding” occurred in more patients in the thrombolysis group (5.4%) than in the dual antiplatelet therapy group (1.6%), and this difference was significant (P = .01).

Subgroup analysis showed a trend toward benefit of alteplase for patients with higher NIHSS score at baseline (NIHSS > 3). Otherwise, the other subgroups looked similar to the main results.

Dr. Nguyen pointed out one limitation of the study – that dual antiplatelet therapy was updated to standard treatment in this target population in the 2019 AHA/ASA guidelines.

In her discussion of the study, Dr. Khatri suggested that the ARAMIS results were what might have been expected.

“Dual antiplatelet therapy is designed to prevent stroke. Even in the POINT trial, dual antiplatelet therapy showed no effect on 90-day functional outcome. It was really about prevention. The PRISMS trial suggested that alteplase was also unlikely to improve 90-day functional outcome in this population of patients with mild and not clearly disabling stroke. So, it is not surprising that dual antiplatelet therapy was noninferior to alteplase for 90-day functional outcome for both those reasons,” she explained.

“That being said, while designed as a noninferiority study, it is interesting to note that alteplase again showed no evidence of treatment effect compared to antiplatelet therapy, affirming what was observed in the prematurely terminated PRISMS trial,” Dr. Khatri added.

In a discussion of the study at an ISC 2023 highlights session, ISC program chair Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., said: “This is very important data and it’s actually the first completed trial that examines this question.”

But, he added, “I think we need to refine our knowledge about what a nondisabling stroke actually is. You could argue that every stroke is disabling. I think we need more clarity on this definition, as in practice, many clinicians still give tPA on account of these mild strokes still being disabling.”

The ARAMIS trial was funded by the National Key R&D Program of China and the Science and Technology Project Plan of Liaoning Province. Dr. Nguyen reports research support from Medtronic that was not related to the current study.

A version of this article first appeared on Medscape.com.

Among Chinese patients with minor nondisabling stroke who presented within 4.5 hours of symptom onset, dual antiplatelet treatment was noninferior to thrombolysis with intravenous alteplase with regard to functional outcome at 90 days in the ARAMIS trial.

The trial was presented by Thanh Nguyen, MD, Boston Medical Center, at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

“Given the ease of administration, less intensive monitoring, low cost, and safety profile of dual antiplatelet therapy, the current findings support the use of dual antiplatelet in this population,” Dr. Nguyen concluded.

In a comment on the trial, Pooja Khatri, MD, professor of neurology at the University of Cincinnati, and lead investigator of the previous PRISMS study of tissue plasminogen activator (tPA) or alteplase in mild stroke, said the results reinforced the current recommendations of giving dual antiplatelet therapy but not alteplase to these patients.

Noting that the standard of care is now to give dual antiplatelet therapy to these patients, Dr. Khatri said: “These data reassure that this remains the right way to go.”

She added that her take-home message from the study would be: “Keep giving dual antiplatelet therapy, and we may be doing more harm than good with alteplase in this patient population.”

Introducing her presentation, Dr. Nguyen explained that mild ischemic stroke, defined as having a National Institutes of Health Stroke Scale (NIHSS) score of 5 or less, comprises half of ischemic stroke patients in the United States. But the benefit of thrombolysis in patients with minor ischemic stroke that is not disabling is unknown.

A subgroup analysis of one of the major thrombolysis trials (IST-3) found that a higher proportion of patients with mild ischemic stroke who were treated within 3 hours of symptom onset were alive and independent at 6 months if they had been given thrombolysis (84%), compared to 65% in the control group who received standard medical treatment.

This led to the first randomized trial (PRISMS) dedicated to patients with mild nondisabling stroke, which found that alteplase given within 3 hours of symptom onset did not increase the likelihood of a good functional outcome at 90 days in comparison with single-agent aspirin. The study was unfortunately terminated early for administrative reasons, and no definitive conclusions could be drawn on the basis of these results, Dr. Nguyen reported.

In 2018, the American Heart Association/American Stroke Association guidelines indicated that for patients who present within 3 hours of symptom onset with mild ischemic stroke that was judged to be nondisabling, thrombolysis with intravenous alteplase could be considered, she noted.

In the meantime, dual antiplatelet therapy was shown to be safe and effective in the POINT and CHANCE trials in patients presenting with minor stroke within 12 or 24 hours, and the CHANCE trial also found a benefit in reducing recurrent stroke that was most effective in the first 2 weeks.

The current ARAMIS trial was therefore conducted to evaluate dual antiplatelet therapy in comparison with thrombolysis for patients with acute minor stroke (NIHSS 5 or less) who presented within 4.5 hours of symptom onset and were without clearly disabling deficit.

The trial was conducted in 38 hospitals in China and included 760 patients (median NIHSS score of 2) who were randomly assigned to receive intravenous alteplase at the standard dose of 0.9 mg/kg, followed by guideline-based antiplatelet treatment, or dual antiplatelet therapy (clopidogrel 300 mg plus 100 mg aspirin loading dose followed by 10 to 14 days of aspirin 100 mg and clopidogrel 75 mg).

The trial was designed to assess noninferiority of dual antiplatelet therapy to alteplase with noninferiority margin of –4.5%.

In the modified intention-to-treat analysis, which included 722 patients, the primary outcome (excellent functional outcome, defined as a Modified Rankin Scale score of 0 or 1 at 90 days) occurred in 93.8% of patients in the dual antiplatelet therapy group and in 91.4% of the alteplase group. This gave a difference of 2.4%, which fell within the limits for noninferiority (P = .0002 for noninferiority test).

“Therefore, this was a positive trial,” Dr. Nguyen stated.

About 20% of patients crossed over from the dual antiplatelet group to the thrombolysis group, and about 16% of patients crossed over from the thrombolysis group to the dual antiplatelet group. But a per-protocol and an “as treated” analysis showed results similar to those of the main intention-to-treat analysis.

Secondary outcomes were largely similar between the two groups other than early neurologic deterioration, which was less common in the dual antiplatelet therapy group.

In terms of safety, symptomatic intracranial hemorrhage occurred in 0.3% (1/369) in the dual antiplatelet group and in 0.9% (3/350) in the alteplase group, a nonsignificant difference.

Events of “any bleeding” occurred in more patients in the thrombolysis group (5.4%) than in the dual antiplatelet therapy group (1.6%), and this difference was significant (P = .01).

Subgroup analysis showed a trend toward benefit of alteplase for patients with higher NIHSS score at baseline (NIHSS > 3). Otherwise, the other subgroups looked similar to the main results.

Dr. Nguyen pointed out one limitation of the study – that dual antiplatelet therapy was updated to standard treatment in this target population in the 2019 AHA/ASA guidelines.

In her discussion of the study, Dr. Khatri suggested that the ARAMIS results were what might have been expected.

“Dual antiplatelet therapy is designed to prevent stroke. Even in the POINT trial, dual antiplatelet therapy showed no effect on 90-day functional outcome. It was really about prevention. The PRISMS trial suggested that alteplase was also unlikely to improve 90-day functional outcome in this population of patients with mild and not clearly disabling stroke. So, it is not surprising that dual antiplatelet therapy was noninferior to alteplase for 90-day functional outcome for both those reasons,” she explained.

“That being said, while designed as a noninferiority study, it is interesting to note that alteplase again showed no evidence of treatment effect compared to antiplatelet therapy, affirming what was observed in the prematurely terminated PRISMS trial,” Dr. Khatri added.

In a discussion of the study at an ISC 2023 highlights session, ISC program chair Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., said: “This is very important data and it’s actually the first completed trial that examines this question.”

But, he added, “I think we need to refine our knowledge about what a nondisabling stroke actually is. You could argue that every stroke is disabling. I think we need more clarity on this definition, as in practice, many clinicians still give tPA on account of these mild strokes still being disabling.”

The ARAMIS trial was funded by the National Key R&D Program of China and the Science and Technology Project Plan of Liaoning Province. Dr. Nguyen reports research support from Medtronic that was not related to the current study.

A version of this article first appeared on Medscape.com.

Among Chinese patients with minor nondisabling stroke who presented within 4.5 hours of symptom onset, dual antiplatelet treatment was noninferior to thrombolysis with intravenous alteplase with regard to functional outcome at 90 days in the ARAMIS trial.

The trial was presented by Thanh Nguyen, MD, Boston Medical Center, at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

“Given the ease of administration, less intensive monitoring, low cost, and safety profile of dual antiplatelet therapy, the current findings support the use of dual antiplatelet in this population,” Dr. Nguyen concluded.

In a comment on the trial, Pooja Khatri, MD, professor of neurology at the University of Cincinnati, and lead investigator of the previous PRISMS study of tissue plasminogen activator (tPA) or alteplase in mild stroke, said the results reinforced the current recommendations of giving dual antiplatelet therapy but not alteplase to these patients.

Noting that the standard of care is now to give dual antiplatelet therapy to these patients, Dr. Khatri said: “These data reassure that this remains the right way to go.”

She added that her take-home message from the study would be: “Keep giving dual antiplatelet therapy, and we may be doing more harm than good with alteplase in this patient population.”

Introducing her presentation, Dr. Nguyen explained that mild ischemic stroke, defined as having a National Institutes of Health Stroke Scale (NIHSS) score of 5 or less, comprises half of ischemic stroke patients in the United States. But the benefit of thrombolysis in patients with minor ischemic stroke that is not disabling is unknown.

A subgroup analysis of one of the major thrombolysis trials (IST-3) found that a higher proportion of patients with mild ischemic stroke who were treated within 3 hours of symptom onset were alive and independent at 6 months if they had been given thrombolysis (84%), compared to 65% in the control group who received standard medical treatment.

This led to the first randomized trial (PRISMS) dedicated to patients with mild nondisabling stroke, which found that alteplase given within 3 hours of symptom onset did not increase the likelihood of a good functional outcome at 90 days in comparison with single-agent aspirin. The study was unfortunately terminated early for administrative reasons, and no definitive conclusions could be drawn on the basis of these results, Dr. Nguyen reported.

In 2018, the American Heart Association/American Stroke Association guidelines indicated that for patients who present within 3 hours of symptom onset with mild ischemic stroke that was judged to be nondisabling, thrombolysis with intravenous alteplase could be considered, she noted.

In the meantime, dual antiplatelet therapy was shown to be safe and effective in the POINT and CHANCE trials in patients presenting with minor stroke within 12 or 24 hours, and the CHANCE trial also found a benefit in reducing recurrent stroke that was most effective in the first 2 weeks.

The current ARAMIS trial was therefore conducted to evaluate dual antiplatelet therapy in comparison with thrombolysis for patients with acute minor stroke (NIHSS 5 or less) who presented within 4.5 hours of symptom onset and were without clearly disabling deficit.

The trial was conducted in 38 hospitals in China and included 760 patients (median NIHSS score of 2) who were randomly assigned to receive intravenous alteplase at the standard dose of 0.9 mg/kg, followed by guideline-based antiplatelet treatment, or dual antiplatelet therapy (clopidogrel 300 mg plus 100 mg aspirin loading dose followed by 10 to 14 days of aspirin 100 mg and clopidogrel 75 mg).

The trial was designed to assess noninferiority of dual antiplatelet therapy to alteplase with noninferiority margin of –4.5%.

In the modified intention-to-treat analysis, which included 722 patients, the primary outcome (excellent functional outcome, defined as a Modified Rankin Scale score of 0 or 1 at 90 days) occurred in 93.8% of patients in the dual antiplatelet therapy group and in 91.4% of the alteplase group. This gave a difference of 2.4%, which fell within the limits for noninferiority (P = .0002 for noninferiority test).

“Therefore, this was a positive trial,” Dr. Nguyen stated.

About 20% of patients crossed over from the dual antiplatelet group to the thrombolysis group, and about 16% of patients crossed over from the thrombolysis group to the dual antiplatelet group. But a per-protocol and an “as treated” analysis showed results similar to those of the main intention-to-treat analysis.

Secondary outcomes were largely similar between the two groups other than early neurologic deterioration, which was less common in the dual antiplatelet therapy group.

In terms of safety, symptomatic intracranial hemorrhage occurred in 0.3% (1/369) in the dual antiplatelet group and in 0.9% (3/350) in the alteplase group, a nonsignificant difference.

Events of “any bleeding” occurred in more patients in the thrombolysis group (5.4%) than in the dual antiplatelet therapy group (1.6%), and this difference was significant (P = .01).

Subgroup analysis showed a trend toward benefit of alteplase for patients with higher NIHSS score at baseline (NIHSS > 3). Otherwise, the other subgroups looked similar to the main results.

Dr. Nguyen pointed out one limitation of the study – that dual antiplatelet therapy was updated to standard treatment in this target population in the 2019 AHA/ASA guidelines.

In her discussion of the study, Dr. Khatri suggested that the ARAMIS results were what might have been expected.

“Dual antiplatelet therapy is designed to prevent stroke. Even in the POINT trial, dual antiplatelet therapy showed no effect on 90-day functional outcome. It was really about prevention. The PRISMS trial suggested that alteplase was also unlikely to improve 90-day functional outcome in this population of patients with mild and not clearly disabling stroke. So, it is not surprising that dual antiplatelet therapy was noninferior to alteplase for 90-day functional outcome for both those reasons,” she explained.

“That being said, while designed as a noninferiority study, it is interesting to note that alteplase again showed no evidence of treatment effect compared to antiplatelet therapy, affirming what was observed in the prematurely terminated PRISMS trial,” Dr. Khatri added.

In a discussion of the study at an ISC 2023 highlights session, ISC program chair Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., said: “This is very important data and it’s actually the first completed trial that examines this question.”

But, he added, “I think we need to refine our knowledge about what a nondisabling stroke actually is. You could argue that every stroke is disabling. I think we need more clarity on this definition, as in practice, many clinicians still give tPA on account of these mild strokes still being disabling.”

The ARAMIS trial was funded by the National Key R&D Program of China and the Science and Technology Project Plan of Liaoning Province. Dr. Nguyen reports research support from Medtronic that was not related to the current study.

A version of this article first appeared on Medscape.com.

Butylphthalide, a medication derived from celery seed, may improve outcomes after an acute ischemic stroke when given in addition to thrombolysis or endovascular treatment, a new report suggests.

Patients treated with butylphthalide had fewer severe neurologic symptoms and better function 90 days after the stroke, compared with those receiving placebo.

Butylphthalide is approved and available for use in China, where the study was conducted. However, the medication hasn’t been approved for use by the U.S. Food and Drug Administration.

“Patients who received butylphthalide had less severe neurological symptoms and a better living status at 90 days post stroke, compared to those who received the placebo,” said coauthor Baixue Jia, MD, an attending physician in interventional neuroradiology at the Beijing Tiantan Hospital of Capital Medical University and a faculty member at the China National Clinical Research Center for Neurological Diseases in Beijing. “If the results are confirmed in other trials, this may lead to more options to treat strokes caused by clots.”

The study was presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
 

Studying stroke outcomes

The researchers described butylphthalide as a cerebroprotective drug that was originally extracted from seeds of Apium graveolens. In China, previous studies have shown that the drug has cerebroprotective effects in animal models of ischemia-reperfusion, they noted.

In this randomized, double-blind, placebo-controlled trial, Dr. Jia and colleagues evaluated whether treatment with butylphthalide could improve 90-day outcomes for adults with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator (tPA), endovascular treatment, or both.

The participants were treated at one of 59 medical centers in China between July 2018 and February 2022. Those who had minimal stroke symptoms on their initial exam, defined as a score of 0-3 on the National Institutes of Health Stroke Scale, or had severe stroke symptoms, defined as having a score of 26 or higher on the NIHSS, were excluded from the study.

Along with an initial revascularization intervention chosen by their physician, participants were randomly selected to receive either butylphthalide or a placebo daily for 90 days. The drug was administered through daily intravenous injections for the first 14 days, after which patients received oral capsules for 76 days.

The research team defined the outcomes as “favorable” if a patient fell into one of the following categories 90 days after the stroke: an initially mild to moderate stroke (NIHSS, 4-7) and no symptoms after treatment, defined as a score of 0 on the Modified Rankin Scale (mRS), which measures disability and dependence; an initially moderate to serious stroke (NIHSS, 8-14) and no residual symptoms or mild symptoms that don’t impair the ability to perform routine activities of daily living without assistance (mRS, 0-1); or an initially serious to severe stroke (NIHSS, 15-25) and no remaining symptoms or a slight disability that impairs some activities but allows one to conduct daily living without assistance (mRS, 0-2).

Secondary outcomes included symptomatic intracranial hemorrhage, recurrent stroke, and mortality.

Among the 1,216 participants, 607 were assigned to the treatment group, and 609 were assigned to the placebo group. The average age was 66 years, and 68% were men.

Overall, participants in the butylphthalide group were 70% more likely to have a favorable 90-day outcome, compared with the placebo group. Favorable outcomes occurred in 344 patients (56.7%) in the butylphthalide group, compared with 268 patients (44%) in the placebo group (odds ratio, 1.70; 95% confidence interval, 1.35-2.14; P < .001).

In addition, butylphthalide improved function equally well for the patients who initially received tPA, those who received endovascular treatment, and those who received both tPA and endovascular treatment.

Secondary events, such as recurrent stroke and intracranial hemorrhage, weren’t significantly different between the butylphthalide and placebo groups.
 

Ongoing questions

Dr. Jia and colleagues noted the need to understand how butylphthalide works in the brain. Animal studies have suggested several possible mechanisms, but it remains unclear.

“The next step should be investigating the exact mechanisms of butylphthalide in humans,” Dr. Jia said.

Additional research should assess the medication in other populations, the authors noted, particularly because the study involved participants who received initial treatment with tPA, endovascular treatment, or both. The results may not be generalizable to stroke patients who receive other treatments or to populations outside of China.

“While these are interesting results, this is only one relatively small study on a fairly select population in China. Butylphthalide, a medication initially compounded from celery seed, is not ready for use in standard stroke treatment,” said Daniel Lackland, DrPH, professor of neurology and director of the division of translational neurosciences and population studies at the Medical University of South Carolina, Charleston.

Dr. Lackland, who wasn’t involved with the study, is a member of the American Stroke Association’s Stroke Council. Although butylphthalide was originally extracted from seeds, he noted, it’s not what patients would find commercially available.

“The medication used in this study is not the same as celery seed or celery seed extract supplements,” he said. “Stroke survivors should always consult with their neurologist or healthcare professional regarding diet after a stroke.”

The study was funded by the National Key Technology Research and Development Program of the Ministry of Science and Technology of the People’s Republic of China and Shijiazhuang Pharmaceutical Group dl-3-butylphthalide Pharmaceutical. Several authors are employed with Beijing Tiantan Hospital and the Beijing Institute of Brain Disorders. Dr. Lackland reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Butylphthalide, a medication derived from celery seed, may improve outcomes after an acute ischemic stroke when given in addition to thrombolysis or endovascular treatment, a new report suggests.

Patients treated with butylphthalide had fewer severe neurologic symptoms and better function 90 days after the stroke, compared with those receiving placebo.

Butylphthalide is approved and available for use in China, where the study was conducted. However, the medication hasn’t been approved for use by the U.S. Food and Drug Administration.

“Patients who received butylphthalide had less severe neurological symptoms and a better living status at 90 days post stroke, compared to those who received the placebo,” said coauthor Baixue Jia, MD, an attending physician in interventional neuroradiology at the Beijing Tiantan Hospital of Capital Medical University and a faculty member at the China National Clinical Research Center for Neurological Diseases in Beijing. “If the results are confirmed in other trials, this may lead to more options to treat strokes caused by clots.”

The study was presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
 

Studying stroke outcomes

The researchers described butylphthalide as a cerebroprotective drug that was originally extracted from seeds of Apium graveolens. In China, previous studies have shown that the drug has cerebroprotective effects in animal models of ischemia-reperfusion, they noted.

In this randomized, double-blind, placebo-controlled trial, Dr. Jia and colleagues evaluated whether treatment with butylphthalide could improve 90-day outcomes for adults with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator (tPA), endovascular treatment, or both.

The participants were treated at one of 59 medical centers in China between July 2018 and February 2022. Those who had minimal stroke symptoms on their initial exam, defined as a score of 0-3 on the National Institutes of Health Stroke Scale, or had severe stroke symptoms, defined as having a score of 26 or higher on the NIHSS, were excluded from the study.

Along with an initial revascularization intervention chosen by their physician, participants were randomly selected to receive either butylphthalide or a placebo daily for 90 days. The drug was administered through daily intravenous injections for the first 14 days, after which patients received oral capsules for 76 days.

The research team defined the outcomes as “favorable” if a patient fell into one of the following categories 90 days after the stroke: an initially mild to moderate stroke (NIHSS, 4-7) and no symptoms after treatment, defined as a score of 0 on the Modified Rankin Scale (mRS), which measures disability and dependence; an initially moderate to serious stroke (NIHSS, 8-14) and no residual symptoms or mild symptoms that don’t impair the ability to perform routine activities of daily living without assistance (mRS, 0-1); or an initially serious to severe stroke (NIHSS, 15-25) and no remaining symptoms or a slight disability that impairs some activities but allows one to conduct daily living without assistance (mRS, 0-2).

Secondary outcomes included symptomatic intracranial hemorrhage, recurrent stroke, and mortality.

Among the 1,216 participants, 607 were assigned to the treatment group, and 609 were assigned to the placebo group. The average age was 66 years, and 68% were men.

Overall, participants in the butylphthalide group were 70% more likely to have a favorable 90-day outcome, compared with the placebo group. Favorable outcomes occurred in 344 patients (56.7%) in the butylphthalide group, compared with 268 patients (44%) in the placebo group (odds ratio, 1.70; 95% confidence interval, 1.35-2.14; P < .001).

In addition, butylphthalide improved function equally well for the patients who initially received tPA, those who received endovascular treatment, and those who received both tPA and endovascular treatment.

Secondary events, such as recurrent stroke and intracranial hemorrhage, weren’t significantly different between the butylphthalide and placebo groups.
 

Ongoing questions

Dr. Jia and colleagues noted the need to understand how butylphthalide works in the brain. Animal studies have suggested several possible mechanisms, but it remains unclear.

“The next step should be investigating the exact mechanisms of butylphthalide in humans,” Dr. Jia said.

Additional research should assess the medication in other populations, the authors noted, particularly because the study involved participants who received initial treatment with tPA, endovascular treatment, or both. The results may not be generalizable to stroke patients who receive other treatments or to populations outside of China.

“While these are interesting results, this is only one relatively small study on a fairly select population in China. Butylphthalide, a medication initially compounded from celery seed, is not ready for use in standard stroke treatment,” said Daniel Lackland, DrPH, professor of neurology and director of the division of translational neurosciences and population studies at the Medical University of South Carolina, Charleston.

Dr. Lackland, who wasn’t involved with the study, is a member of the American Stroke Association’s Stroke Council. Although butylphthalide was originally extracted from seeds, he noted, it’s not what patients would find commercially available.

“The medication used in this study is not the same as celery seed or celery seed extract supplements,” he said. “Stroke survivors should always consult with their neurologist or healthcare professional regarding diet after a stroke.”

The study was funded by the National Key Technology Research and Development Program of the Ministry of Science and Technology of the People’s Republic of China and Shijiazhuang Pharmaceutical Group dl-3-butylphthalide Pharmaceutical. Several authors are employed with Beijing Tiantan Hospital and the Beijing Institute of Brain Disorders. Dr. Lackland reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Butylphthalide, a medication derived from celery seed, may improve outcomes after an acute ischemic stroke when given in addition to thrombolysis or endovascular treatment, a new report suggests.

Patients treated with butylphthalide had fewer severe neurologic symptoms and better function 90 days after the stroke, compared with those receiving placebo.

Butylphthalide is approved and available for use in China, where the study was conducted. However, the medication hasn’t been approved for use by the U.S. Food and Drug Administration.

“Patients who received butylphthalide had less severe neurological symptoms and a better living status at 90 days post stroke, compared to those who received the placebo,” said coauthor Baixue Jia, MD, an attending physician in interventional neuroradiology at the Beijing Tiantan Hospital of Capital Medical University and a faculty member at the China National Clinical Research Center for Neurological Diseases in Beijing. “If the results are confirmed in other trials, this may lead to more options to treat strokes caused by clots.”

The study was presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
 

Studying stroke outcomes

The researchers described butylphthalide as a cerebroprotective drug that was originally extracted from seeds of Apium graveolens. In China, previous studies have shown that the drug has cerebroprotective effects in animal models of ischemia-reperfusion, they noted.

In this randomized, double-blind, placebo-controlled trial, Dr. Jia and colleagues evaluated whether treatment with butylphthalide could improve 90-day outcomes for adults with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator (tPA), endovascular treatment, or both.

The participants were treated at one of 59 medical centers in China between July 2018 and February 2022. Those who had minimal stroke symptoms on their initial exam, defined as a score of 0-3 on the National Institutes of Health Stroke Scale, or had severe stroke symptoms, defined as having a score of 26 or higher on the NIHSS, were excluded from the study.

Along with an initial revascularization intervention chosen by their physician, participants were randomly selected to receive either butylphthalide or a placebo daily for 90 days. The drug was administered through daily intravenous injections for the first 14 days, after which patients received oral capsules for 76 days.

The research team defined the outcomes as “favorable” if a patient fell into one of the following categories 90 days after the stroke: an initially mild to moderate stroke (NIHSS, 4-7) and no symptoms after treatment, defined as a score of 0 on the Modified Rankin Scale (mRS), which measures disability and dependence; an initially moderate to serious stroke (NIHSS, 8-14) and no residual symptoms or mild symptoms that don’t impair the ability to perform routine activities of daily living without assistance (mRS, 0-1); or an initially serious to severe stroke (NIHSS, 15-25) and no remaining symptoms or a slight disability that impairs some activities but allows one to conduct daily living without assistance (mRS, 0-2).

Secondary outcomes included symptomatic intracranial hemorrhage, recurrent stroke, and mortality.

Among the 1,216 participants, 607 were assigned to the treatment group, and 609 were assigned to the placebo group. The average age was 66 years, and 68% were men.

Overall, participants in the butylphthalide group were 70% more likely to have a favorable 90-day outcome, compared with the placebo group. Favorable outcomes occurred in 344 patients (56.7%) in the butylphthalide group, compared with 268 patients (44%) in the placebo group (odds ratio, 1.70; 95% confidence interval, 1.35-2.14; P < .001).

In addition, butylphthalide improved function equally well for the patients who initially received tPA, those who received endovascular treatment, and those who received both tPA and endovascular treatment.

Secondary events, such as recurrent stroke and intracranial hemorrhage, weren’t significantly different between the butylphthalide and placebo groups.
 

Ongoing questions

Dr. Jia and colleagues noted the need to understand how butylphthalide works in the brain. Animal studies have suggested several possible mechanisms, but it remains unclear.

“The next step should be investigating the exact mechanisms of butylphthalide in humans,” Dr. Jia said.

Additional research should assess the medication in other populations, the authors noted, particularly because the study involved participants who received initial treatment with tPA, endovascular treatment, or both. The results may not be generalizable to stroke patients who receive other treatments or to populations outside of China.

“While these are interesting results, this is only one relatively small study on a fairly select population in China. Butylphthalide, a medication initially compounded from celery seed, is not ready for use in standard stroke treatment,” said Daniel Lackland, DrPH, professor of neurology and director of the division of translational neurosciences and population studies at the Medical University of South Carolina, Charleston.

Dr. Lackland, who wasn’t involved with the study, is a member of the American Stroke Association’s Stroke Council. Although butylphthalide was originally extracted from seeds, he noted, it’s not what patients would find commercially available.

“The medication used in this study is not the same as celery seed or celery seed extract supplements,” he said. “Stroke survivors should always consult with their neurologist or healthcare professional regarding diet after a stroke.”

The study was funded by the National Key Technology Research and Development Program of the Ministry of Science and Technology of the People’s Republic of China and Shijiazhuang Pharmaceutical Group dl-3-butylphthalide Pharmaceutical. Several authors are employed with Beijing Tiantan Hospital and the Beijing Institute of Brain Disorders. Dr. Lackland reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A combination of two drugs has shown promising results, including a reduction in cognitive impairment in patients who have had a lacunar stroke, and is seen as a new therapeutic approach for patients with cerebral small-vessel disease. The drugs – isosorbide mononitrate and cilostazol – stabilize endothelial function, which is a new therapeutic target for patients with small-vessel disease stroke.

The phase 2 LACI-2 study, evaluating these drugs individually and in combination in patients with lacunar stroke, showed promising trends toward reductions in recurrent stroke, cognitive impairment, and dependency, some of which became significant when the drugs were given together. There was also some suggestion of positive impacts on mood and quality of life.

“Isosorbide mononitrate was associated with a reduction in recurrent stroke, a tendency toward a reduction in dependency and a reduction in cognitive impairment, and cilostazol also seemed to reduce dependency,” study investigator Joanna M. Wardlaw, MD, professor of applied neuroimaging at Edinburgh University, reported.

“When used together, they seemed to have more benefits than either drug on its own. So this is good preliminary evidence that the drugs are working together in a positive way,” she said. But she cautioned that these potential benefits will need to be confirmed in a larger phase 3 trial.

The LACI-2 study was presented at the International Stroke Conference by Dr. Wardlaw and coinvestigator Philip Bath, DSc, professor of medicine at the University of Nottingham (England).

They both highlighted the effect seen on cognitive impairment at the conference presented by the American Stroke Association, a division of the American Heart Association.

“We saw a significant reduction in the number of patients with cognitive impairment with the two drugs together in this phase 2 study,” Dr. Wardlaw said. “This is very encouraging since no study has previously found any medications that positively affect cognitive impairment in small-vessel disease strokes. We cautiously hope that these medications may have wider implications for other types of small-vessel disease as well.”

Dr. Bath added: “The results on cognitive impairment are particularly important. Many patients rate cognitive impairment as one of the most dreaded outcomes of a stroke even if they also have quite significant physical disability. People simply don’t want to lose their memory and thinking ability.”

“The results of LACI-2 also raise interesting questions about whether these drugs would be beneficial for other types of small-vessel disease which do not present as stroke, but maybe may manifest as headaches or memory impairment,” he noted.
 

‘Very intriguing results’

Outside experts were enthusiastic about these preliminary results. In an ISC highlights presentation, program chair Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., said: “It is refreshing to finally see some positive signals in studies in small-vessel stroke. This is an area where we haven’t had answers for a long time.”

He described the reduction in cognitive impairment seen in the study as “very intriguing and very important.”

“I think we have underestimated the burden that cognitive impairment has in stroke, and the burden in general in society of vascular cognitive impairment. This is a very promising approach that definitely deserves to be investigated more thoroughly in a larger trial.”

Commenting on the study findings, Mitchell Elkind, MD, professor of neurology and epidemiology at Columbia University Irving Medical Center, New York, said this study “provides evidence that points us in at least two important directions.”

“First, it suggests that endothelial dysfunction, or problems with the lining of the blood vessels, may be an important contributor to small-vessel disease and the cognitive decline that often accompanies it. This is a new mechanism of action and different from blood clotting, blood pressure, and other conventional targets of treatment,” Dr. Elkind said.

“Second, and more generally, it suggests that stroke trials, particularly in the subtype of small-vessel disease, can and should explore not only the incidence of recurrent acute events but also the steady decline that occurs after stroke. Poststroke cognitive decline is a relatively new area of stroke research.”

Dr. Wardlaw noted that lacunar stroke is a common type of ischemic stroke, but it has been rather neglected in terms of research. It is assumed to be caused by atherosclerosis of the small vessel but there is now mounting evidence suggesting that it is a result of problems in the endothelium of the small vessels.  

“We looked for potential available drugs that targeted endothelial dysfunction. Both the drugs we tested are already widely used – isosorbide mononitrate for the treatment of coronary artery disease and angina, and cilostazol, mainly in Asia, for stroke prevention,” she said.  

LACI-2 was primarily a feasibility study looking at whether it was possible to recruit enough patients who had had a lacunar stroke and would take the drugs, individually or in combination, for up to a year. Outcomes were investigated on an exploratory basis. The study enrolled 363 patients who had experienced lacunar stroke from 26 stroke centers throughout the United Kingdom. They were randomly assigned to one of four treatment groups for 1 year:

• 40-60 mg/day of oral isosorbide mononitrate alone.
• 200 mg/day of oral cilostazol alone.
• Both medications.
• Neither medication.

Patients completed phone surveys at 6 and 12 months to assess health status, including recurrent stroke, myocardial infarction, cognitive tests, symptoms, quality of life surveys, and they also had brain imaging at 12 months.

Results showed 98% of patients were still taking their study medication at 1 year, and the drugs appeared to be safe on top of usual care with few deaths or hemorrhages in the study.

The composite outcome including recurrent stroke, MI, cognitive impairment, dependency (modified Rankin score > 2) and death was reduced by 20% in the isosorbide mononitrate–alone group (adjusted hazard ratio, 0.80; 95% confidence interval, 0.59-1.09).

The composite endpoint was reduced by 23% in the cilostazol group (aHR, 0.77; 95% CI, 0.57-1.05) and by 42% in the combination group (aHR, 0.58, 95% CI, 0.36-0.92) compared with those taking neither drug.

Isosorbide mononitrate alone showed trends toward a reduction in recurrent stroke, cognitive impairment, and dependency, whereas cilostazol alone reduced dependency with a trend toward a reduction in cognitive impairment. When used together, the drugs showed large reductions in cognitive impairment (aHR, 0.44; 95% CI, 0.19-0.99) and dependency (aHR ,0.14; 95% CI, 0.03-0.59).

During the highlights session, Dr. Jovin commented: “It is obvious that the investigators have put a lot of thought into the design of this trial. Presumably because of the composite score they were able to increase the power. We are used to trials which require thousands of patients, but here we are able to see significant results, although exploratory, with just a few hundred patients.”

Dr. Bath stressed that this was only a phase 2 study. “We now need to see if we can confirm these results in a larger phase 3 study.” That study, LACI-3, is planned to start later this year. He also suggested that it would be interesting to investigate whether these drugs would work in other types of ischemic stroke such as those caused by large-artery disease or cardioembolic strokes, as well as other forms of small-vessel disease such as patients with vascular cognitive impairment.

“There are many areas to investigate in future. It might be that in a few years’ time these drugs may be standard of care across many different forms of small-vessel disease,” he said.

Dr. Wardlaw noted that lacunar strokes are generally quite mild strokes, which could be one of the reasons why they have not been the target of much research to date. But Dr. Bath added: “While they may be labeled as a mild stroke on the NIHSS scale, patients can still be quite badly affected. About half of patients with a lacunar stroke develop cognitive impairment and eventually dementia – that is certainly not mild.”

The study was funded primarily by the British Heart Foundation, with support from the UK Alzheimer’s Society, the UK Dementia Research Institute, the Stroke Association, the Fondation Leducq, NHS Research Scotland, and the UK National Institutes of Health Research Clinical Research Networks. Dr. Bath is an adviser to CoMind, DiaMedica, Phagenesis, and Roche. Dr. Wardlaw reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A combination of two drugs has shown promising results, including a reduction in cognitive impairment in patients who have had a lacunar stroke, and is seen as a new therapeutic approach for patients with cerebral small-vessel disease. The drugs – isosorbide mononitrate and cilostazol – stabilize endothelial function, which is a new therapeutic target for patients with small-vessel disease stroke.

The phase 2 LACI-2 study, evaluating these drugs individually and in combination in patients with lacunar stroke, showed promising trends toward reductions in recurrent stroke, cognitive impairment, and dependency, some of which became significant when the drugs were given together. There was also some suggestion of positive impacts on mood and quality of life.

“Isosorbide mononitrate was associated with a reduction in recurrent stroke, a tendency toward a reduction in dependency and a reduction in cognitive impairment, and cilostazol also seemed to reduce dependency,” study investigator Joanna M. Wardlaw, MD, professor of applied neuroimaging at Edinburgh University, reported.

“When used together, they seemed to have more benefits than either drug on its own. So this is good preliminary evidence that the drugs are working together in a positive way,” she said. But she cautioned that these potential benefits will need to be confirmed in a larger phase 3 trial.

The LACI-2 study was presented at the International Stroke Conference by Dr. Wardlaw and coinvestigator Philip Bath, DSc, professor of medicine at the University of Nottingham (England).

They both highlighted the effect seen on cognitive impairment at the conference presented by the American Stroke Association, a division of the American Heart Association.

“We saw a significant reduction in the number of patients with cognitive impairment with the two drugs together in this phase 2 study,” Dr. Wardlaw said. “This is very encouraging since no study has previously found any medications that positively affect cognitive impairment in small-vessel disease strokes. We cautiously hope that these medications may have wider implications for other types of small-vessel disease as well.”

Dr. Bath added: “The results on cognitive impairment are particularly important. Many patients rate cognitive impairment as one of the most dreaded outcomes of a stroke even if they also have quite significant physical disability. People simply don’t want to lose their memory and thinking ability.”

“The results of LACI-2 also raise interesting questions about whether these drugs would be beneficial for other types of small-vessel disease which do not present as stroke, but maybe may manifest as headaches or memory impairment,” he noted.
 

‘Very intriguing results’

Outside experts were enthusiastic about these preliminary results. In an ISC highlights presentation, program chair Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., said: “It is refreshing to finally see some positive signals in studies in small-vessel stroke. This is an area where we haven’t had answers for a long time.”

He described the reduction in cognitive impairment seen in the study as “very intriguing and very important.”

“I think we have underestimated the burden that cognitive impairment has in stroke, and the burden in general in society of vascular cognitive impairment. This is a very promising approach that definitely deserves to be investigated more thoroughly in a larger trial.”

Commenting on the study findings, Mitchell Elkind, MD, professor of neurology and epidemiology at Columbia University Irving Medical Center, New York, said this study “provides evidence that points us in at least two important directions.”

“First, it suggests that endothelial dysfunction, or problems with the lining of the blood vessels, may be an important contributor to small-vessel disease and the cognitive decline that often accompanies it. This is a new mechanism of action and different from blood clotting, blood pressure, and other conventional targets of treatment,” Dr. Elkind said.

“Second, and more generally, it suggests that stroke trials, particularly in the subtype of small-vessel disease, can and should explore not only the incidence of recurrent acute events but also the steady decline that occurs after stroke. Poststroke cognitive decline is a relatively new area of stroke research.”

Dr. Wardlaw noted that lacunar stroke is a common type of ischemic stroke, but it has been rather neglected in terms of research. It is assumed to be caused by atherosclerosis of the small vessel but there is now mounting evidence suggesting that it is a result of problems in the endothelium of the small vessels.  

“We looked for potential available drugs that targeted endothelial dysfunction. Both the drugs we tested are already widely used – isosorbide mononitrate for the treatment of coronary artery disease and angina, and cilostazol, mainly in Asia, for stroke prevention,” she said.  

LACI-2 was primarily a feasibility study looking at whether it was possible to recruit enough patients who had had a lacunar stroke and would take the drugs, individually or in combination, for up to a year. Outcomes were investigated on an exploratory basis. The study enrolled 363 patients who had experienced lacunar stroke from 26 stroke centers throughout the United Kingdom. They were randomly assigned to one of four treatment groups for 1 year:

• 40-60 mg/day of oral isosorbide mononitrate alone.
• 200 mg/day of oral cilostazol alone.
• Both medications.
• Neither medication.

Patients completed phone surveys at 6 and 12 months to assess health status, including recurrent stroke, myocardial infarction, cognitive tests, symptoms, quality of life surveys, and they also had brain imaging at 12 months.

Results showed 98% of patients were still taking their study medication at 1 year, and the drugs appeared to be safe on top of usual care with few deaths or hemorrhages in the study.

The composite outcome including recurrent stroke, MI, cognitive impairment, dependency (modified Rankin score > 2) and death was reduced by 20% in the isosorbide mononitrate–alone group (adjusted hazard ratio, 0.80; 95% confidence interval, 0.59-1.09).

The composite endpoint was reduced by 23% in the cilostazol group (aHR, 0.77; 95% CI, 0.57-1.05) and by 42% in the combination group (aHR, 0.58, 95% CI, 0.36-0.92) compared with those taking neither drug.

Isosorbide mononitrate alone showed trends toward a reduction in recurrent stroke, cognitive impairment, and dependency, whereas cilostazol alone reduced dependency with a trend toward a reduction in cognitive impairment. When used together, the drugs showed large reductions in cognitive impairment (aHR, 0.44; 95% CI, 0.19-0.99) and dependency (aHR ,0.14; 95% CI, 0.03-0.59).

During the highlights session, Dr. Jovin commented: “It is obvious that the investigators have put a lot of thought into the design of this trial. Presumably because of the composite score they were able to increase the power. We are used to trials which require thousands of patients, but here we are able to see significant results, although exploratory, with just a few hundred patients.”

Dr. Bath stressed that this was only a phase 2 study. “We now need to see if we can confirm these results in a larger phase 3 study.” That study, LACI-3, is planned to start later this year. He also suggested that it would be interesting to investigate whether these drugs would work in other types of ischemic stroke such as those caused by large-artery disease or cardioembolic strokes, as well as other forms of small-vessel disease such as patients with vascular cognitive impairment.

“There are many areas to investigate in future. It might be that in a few years’ time these drugs may be standard of care across many different forms of small-vessel disease,” he said.

Dr. Wardlaw noted that lacunar strokes are generally quite mild strokes, which could be one of the reasons why they have not been the target of much research to date. But Dr. Bath added: “While they may be labeled as a mild stroke on the NIHSS scale, patients can still be quite badly affected. About half of patients with a lacunar stroke develop cognitive impairment and eventually dementia – that is certainly not mild.”

The study was funded primarily by the British Heart Foundation, with support from the UK Alzheimer’s Society, the UK Dementia Research Institute, the Stroke Association, the Fondation Leducq, NHS Research Scotland, and the UK National Institutes of Health Research Clinical Research Networks. Dr. Bath is an adviser to CoMind, DiaMedica, Phagenesis, and Roche. Dr. Wardlaw reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A combination of two drugs has shown promising results, including a reduction in cognitive impairment in patients who have had a lacunar stroke, and is seen as a new therapeutic approach for patients with cerebral small-vessel disease. The drugs – isosorbide mononitrate and cilostazol – stabilize endothelial function, which is a new therapeutic target for patients with small-vessel disease stroke.

The phase 2 LACI-2 study, evaluating these drugs individually and in combination in patients with lacunar stroke, showed promising trends toward reductions in recurrent stroke, cognitive impairment, and dependency, some of which became significant when the drugs were given together. There was also some suggestion of positive impacts on mood and quality of life.

“Isosorbide mononitrate was associated with a reduction in recurrent stroke, a tendency toward a reduction in dependency and a reduction in cognitive impairment, and cilostazol also seemed to reduce dependency,” study investigator Joanna M. Wardlaw, MD, professor of applied neuroimaging at Edinburgh University, reported.

“When used together, they seemed to have more benefits than either drug on its own. So this is good preliminary evidence that the drugs are working together in a positive way,” she said. But she cautioned that these potential benefits will need to be confirmed in a larger phase 3 trial.

The LACI-2 study was presented at the International Stroke Conference by Dr. Wardlaw and coinvestigator Philip Bath, DSc, professor of medicine at the University of Nottingham (England).

They both highlighted the effect seen on cognitive impairment at the conference presented by the American Stroke Association, a division of the American Heart Association.

“We saw a significant reduction in the number of patients with cognitive impairment with the two drugs together in this phase 2 study,” Dr. Wardlaw said. “This is very encouraging since no study has previously found any medications that positively affect cognitive impairment in small-vessel disease strokes. We cautiously hope that these medications may have wider implications for other types of small-vessel disease as well.”

Dr. Bath added: “The results on cognitive impairment are particularly important. Many patients rate cognitive impairment as one of the most dreaded outcomes of a stroke even if they also have quite significant physical disability. People simply don’t want to lose their memory and thinking ability.”

“The results of LACI-2 also raise interesting questions about whether these drugs would be beneficial for other types of small-vessel disease which do not present as stroke, but maybe may manifest as headaches or memory impairment,” he noted.
 

‘Very intriguing results’

Outside experts were enthusiastic about these preliminary results. In an ISC highlights presentation, program chair Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., said: “It is refreshing to finally see some positive signals in studies in small-vessel stroke. This is an area where we haven’t had answers for a long time.”

He described the reduction in cognitive impairment seen in the study as “very intriguing and very important.”

“I think we have underestimated the burden that cognitive impairment has in stroke, and the burden in general in society of vascular cognitive impairment. This is a very promising approach that definitely deserves to be investigated more thoroughly in a larger trial.”

Commenting on the study findings, Mitchell Elkind, MD, professor of neurology and epidemiology at Columbia University Irving Medical Center, New York, said this study “provides evidence that points us in at least two important directions.”

“First, it suggests that endothelial dysfunction, or problems with the lining of the blood vessels, may be an important contributor to small-vessel disease and the cognitive decline that often accompanies it. This is a new mechanism of action and different from blood clotting, blood pressure, and other conventional targets of treatment,” Dr. Elkind said.

“Second, and more generally, it suggests that stroke trials, particularly in the subtype of small-vessel disease, can and should explore not only the incidence of recurrent acute events but also the steady decline that occurs after stroke. Poststroke cognitive decline is a relatively new area of stroke research.”

Dr. Wardlaw noted that lacunar stroke is a common type of ischemic stroke, but it has been rather neglected in terms of research. It is assumed to be caused by atherosclerosis of the small vessel but there is now mounting evidence suggesting that it is a result of problems in the endothelium of the small vessels.  

“We looked for potential available drugs that targeted endothelial dysfunction. Both the drugs we tested are already widely used – isosorbide mononitrate for the treatment of coronary artery disease and angina, and cilostazol, mainly in Asia, for stroke prevention,” she said.  

LACI-2 was primarily a feasibility study looking at whether it was possible to recruit enough patients who had had a lacunar stroke and would take the drugs, individually or in combination, for up to a year. Outcomes were investigated on an exploratory basis. The study enrolled 363 patients who had experienced lacunar stroke from 26 stroke centers throughout the United Kingdom. They were randomly assigned to one of four treatment groups for 1 year:

• 40-60 mg/day of oral isosorbide mononitrate alone.
• 200 mg/day of oral cilostazol alone.
• Both medications.
• Neither medication.

Patients completed phone surveys at 6 and 12 months to assess health status, including recurrent stroke, myocardial infarction, cognitive tests, symptoms, quality of life surveys, and they also had brain imaging at 12 months.

Results showed 98% of patients were still taking their study medication at 1 year, and the drugs appeared to be safe on top of usual care with few deaths or hemorrhages in the study.

The composite outcome including recurrent stroke, MI, cognitive impairment, dependency (modified Rankin score > 2) and death was reduced by 20% in the isosorbide mononitrate–alone group (adjusted hazard ratio, 0.80; 95% confidence interval, 0.59-1.09).

The composite endpoint was reduced by 23% in the cilostazol group (aHR, 0.77; 95% CI, 0.57-1.05) and by 42% in the combination group (aHR, 0.58, 95% CI, 0.36-0.92) compared with those taking neither drug.

Isosorbide mononitrate alone showed trends toward a reduction in recurrent stroke, cognitive impairment, and dependency, whereas cilostazol alone reduced dependency with a trend toward a reduction in cognitive impairment. When used together, the drugs showed large reductions in cognitive impairment (aHR, 0.44; 95% CI, 0.19-0.99) and dependency (aHR ,0.14; 95% CI, 0.03-0.59).

During the highlights session, Dr. Jovin commented: “It is obvious that the investigators have put a lot of thought into the design of this trial. Presumably because of the composite score they were able to increase the power. We are used to trials which require thousands of patients, but here we are able to see significant results, although exploratory, with just a few hundred patients.”

Dr. Bath stressed that this was only a phase 2 study. “We now need to see if we can confirm these results in a larger phase 3 study.” That study, LACI-3, is planned to start later this year. He also suggested that it would be interesting to investigate whether these drugs would work in other types of ischemic stroke such as those caused by large-artery disease or cardioembolic strokes, as well as other forms of small-vessel disease such as patients with vascular cognitive impairment.

“There are many areas to investigate in future. It might be that in a few years’ time these drugs may be standard of care across many different forms of small-vessel disease,” he said.

Dr. Wardlaw noted that lacunar strokes are generally quite mild strokes, which could be one of the reasons why they have not been the target of much research to date. But Dr. Bath added: “While they may be labeled as a mild stroke on the NIHSS scale, patients can still be quite badly affected. About half of patients with a lacunar stroke develop cognitive impairment and eventually dementia – that is certainly not mild.”

The study was funded primarily by the British Heart Foundation, with support from the UK Alzheimer’s Society, the UK Dementia Research Institute, the Stroke Association, the Fondation Leducq, NHS Research Scotland, and the UK National Institutes of Health Research Clinical Research Networks. Dr. Bath is an adviser to CoMind, DiaMedica, Phagenesis, and Roche. Dr. Wardlaw reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Tenecteplase is as effective as alteplase with respect to disability outcomes and safety in Chinese patients with ischemic stroke, a new study has found. “This was a pivotal trial in establishing the safety and efficacy of tenecteplase as an alternative to alteplase in the thrombolytic treatment of acute ischemic stroke within 4.5 hours in Asian patients,” said study author Shuya Li, MD, associate chief physician, department of neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing.

The findings in this all-Chinese population should have an impact on the use of tenecteplase going forward, said Dr. Li. “The results provide further evidence to support a worldwide switch to tenecteplase as the preferred thrombolytic for acute ischemic stroke.”

The findings were presented at the 2023 International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
 

Single bolus

Use of alteplase (tissue plasminogen activator [tPA]) has for years been the main approach to thrombolytic reperfusion therapy for patients with acute stroke, but tenecteplase has recently emerged as a potential successor.

Tenecteplase is a tPA produced by recombinant DNA technology. It has a relatively long half-life and can be delivered in a single bolus instead of requiring an hour-long infusion, as is the case with alteplase.

The phase 3 noninferiority Tenecteplase Reperfusion Therapy in Acute ischemic Cerebrovascular Events (TRACE-2) trial – the first of its kind in an Asian population – included 1,430 adult ischemic stroke patients at 53 Chinese centers. Patients had to have a National Institutes of Health Stroke Scale (NIHSS) score of 5-25 and either not be eligible for or have refused endovascular therapy.

The mean age of study participants was about 66 years, and the percentage of women was about 31%. The mean baseline NIHSS score was 7 in both groups, and the symptom-onset-to-needle time was similar at 180 minutes for the tenecteplase group and 178.5 minutes for the alteplase group.

Researchers randomly assigned patients to receive tenecteplase or alteplase within 4.5 hours of symptom onset.

Those in the tenecteplase group received 0.25 mg/kg of the drug in a single IV bolus (maximum dose, 25 mg). Control group members who were treated with alteplase were given the drug as a 10% bolus, with the remainder given as a 1-hour infusion (0.9 mg/kg with a maximum dose of 90 mg).
 

Showed noninferiority

The primary efficacy outcome was a modified Rankins scale (mRS) score of 0-1 at 90 days, which is considered excellent function. About 62% of tenecteplase patients and 58% of alteplase patients attained this outcome (risk ratio, 1.09; 95% confidence interval, 1.00-1.18).

The P value was .001 for noninferiority and .06 for superiority, but Dr. Li explained that these values may change when considering the site effect.

There were no statistically significant differences between the two drugs on secondary outcomes of favorable function. For example, 73% of tenecteplase patients and 72% of alteplase patients had an mRS score of 0-2 at 3 months, and 50% in the tenecteplase and 49% in the alteplase group improved by 4 or more points on the NIHSS, or had a score of 1 or less, at 24 hours.

The groups also had comparable scores on the European quality-of-life visual analogue scale and on the Barthel index, which measures functional independence related to personal care and mobility.

Tenecteplase also turned out to be as safe at alteplase. About 2% in both groups had symptomatic intracranial hemorrhage within 36 hours, and both groups had that same percentage for such hemorrhages within 90 days. As well, the groups had a similar rate of any intracranial hemorrhage within 90 days (6% and 7%).

The mortality rate was 7% in the tenecteplase group, compared with 5% in the alteplase group.

Adverse events (AEs) occurred in 86% and 87%, and serious AEs in 16% and 15%, of the tenecteplase and alteplase groups, respectively, again with no statistically significant differences.

The research team aims to test the effectiveness of tenecteplase in other stroke patients, including those with minor strokes, those receiving thrombolysis in a later window, and those receiving endovascular therapy, said Dr. Li.
 

Strong evidence

Commenting on the study findings, Larry B. Goldstein, MD, professor and chair of neurology, University of Kentucky, Lexington, said it is important to determine the efficacy of tenecteplase among Asians, as they represent “an entirely different population” with unique concerns, such as bleeding complications from anticoagulants.

He noted an advantage of tenecteplase is ease of administration. “You don’t have to go through the loading dose and then the 1-hour infusion,” which poses an “additional hassle” when transferring patients between institutions, he said.

However, he noted that a possible “downside” to having both drugs available in the emergency department is “using the wrong drug at the wrong dose” because of their similar sounding names.

Also commenting on the study, Tudor G. Jovin, MD, professor and chair, department of neurology, Rowan University, Camden, N.J., said he welcomes another trial that confirms that these two drugs are biologically similar.

“I’m very glad this trial was done because it adds another very strong piece of evidence of equivalency.”

But the two drugs are not the same in some important respects, said Dr. Jovin, whose center switched to using tenecteplase almost 3 years ago. That switch has resulted in cutting 17 minutes from the door-to-needle time “which is quite significant,” he said.

“There’s no question that once we used tenecteplase in lieu of tPA, it’s been just so much easier to administer and affects the interhospital transfer protocols, because you’re not transferring the patient with a critical care IV. It’s a win-win situation for everyone.”

The study received funding from the National Science and Technology Major Project, the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, and the China Shijiazhuang Pharmaceutical Company Recomgen Pharmaceutical (Guangzhou). Dr. Li, Dr. Goldstein, and Dr. Jovin report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Tenecteplase is as effective as alteplase with respect to disability outcomes and safety in Chinese patients with ischemic stroke, a new study has found. “This was a pivotal trial in establishing the safety and efficacy of tenecteplase as an alternative to alteplase in the thrombolytic treatment of acute ischemic stroke within 4.5 hours in Asian patients,” said study author Shuya Li, MD, associate chief physician, department of neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing.

The findings in this all-Chinese population should have an impact on the use of tenecteplase going forward, said Dr. Li. “The results provide further evidence to support a worldwide switch to tenecteplase as the preferred thrombolytic for acute ischemic stroke.”

The findings were presented at the 2023 International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
 

Single bolus

Use of alteplase (tissue plasminogen activator [tPA]) has for years been the main approach to thrombolytic reperfusion therapy for patients with acute stroke, but tenecteplase has recently emerged as a potential successor.

Tenecteplase is a tPA produced by recombinant DNA technology. It has a relatively long half-life and can be delivered in a single bolus instead of requiring an hour-long infusion, as is the case with alteplase.

The phase 3 noninferiority Tenecteplase Reperfusion Therapy in Acute ischemic Cerebrovascular Events (TRACE-2) trial – the first of its kind in an Asian population – included 1,430 adult ischemic stroke patients at 53 Chinese centers. Patients had to have a National Institutes of Health Stroke Scale (NIHSS) score of 5-25 and either not be eligible for or have refused endovascular therapy.

The mean age of study participants was about 66 years, and the percentage of women was about 31%. The mean baseline NIHSS score was 7 in both groups, and the symptom-onset-to-needle time was similar at 180 minutes for the tenecteplase group and 178.5 minutes for the alteplase group.

Researchers randomly assigned patients to receive tenecteplase or alteplase within 4.5 hours of symptom onset.

Those in the tenecteplase group received 0.25 mg/kg of the drug in a single IV bolus (maximum dose, 25 mg). Control group members who were treated with alteplase were given the drug as a 10% bolus, with the remainder given as a 1-hour infusion (0.9 mg/kg with a maximum dose of 90 mg).
 

Showed noninferiority

The primary efficacy outcome was a modified Rankins scale (mRS) score of 0-1 at 90 days, which is considered excellent function. About 62% of tenecteplase patients and 58% of alteplase patients attained this outcome (risk ratio, 1.09; 95% confidence interval, 1.00-1.18).

The P value was .001 for noninferiority and .06 for superiority, but Dr. Li explained that these values may change when considering the site effect.

There were no statistically significant differences between the two drugs on secondary outcomes of favorable function. For example, 73% of tenecteplase patients and 72% of alteplase patients had an mRS score of 0-2 at 3 months, and 50% in the tenecteplase and 49% in the alteplase group improved by 4 or more points on the NIHSS, or had a score of 1 or less, at 24 hours.

The groups also had comparable scores on the European quality-of-life visual analogue scale and on the Barthel index, which measures functional independence related to personal care and mobility.

Tenecteplase also turned out to be as safe at alteplase. About 2% in both groups had symptomatic intracranial hemorrhage within 36 hours, and both groups had that same percentage for such hemorrhages within 90 days. As well, the groups had a similar rate of any intracranial hemorrhage within 90 days (6% and 7%).

The mortality rate was 7% in the tenecteplase group, compared with 5% in the alteplase group.

Adverse events (AEs) occurred in 86% and 87%, and serious AEs in 16% and 15%, of the tenecteplase and alteplase groups, respectively, again with no statistically significant differences.

The research team aims to test the effectiveness of tenecteplase in other stroke patients, including those with minor strokes, those receiving thrombolysis in a later window, and those receiving endovascular therapy, said Dr. Li.
 

Strong evidence

Commenting on the study findings, Larry B. Goldstein, MD, professor and chair of neurology, University of Kentucky, Lexington, said it is important to determine the efficacy of tenecteplase among Asians, as they represent “an entirely different population” with unique concerns, such as bleeding complications from anticoagulants.

He noted an advantage of tenecteplase is ease of administration. “You don’t have to go through the loading dose and then the 1-hour infusion,” which poses an “additional hassle” when transferring patients between institutions, he said.

However, he noted that a possible “downside” to having both drugs available in the emergency department is “using the wrong drug at the wrong dose” because of their similar sounding names.

Also commenting on the study, Tudor G. Jovin, MD, professor and chair, department of neurology, Rowan University, Camden, N.J., said he welcomes another trial that confirms that these two drugs are biologically similar.

“I’m very glad this trial was done because it adds another very strong piece of evidence of equivalency.”

But the two drugs are not the same in some important respects, said Dr. Jovin, whose center switched to using tenecteplase almost 3 years ago. That switch has resulted in cutting 17 minutes from the door-to-needle time “which is quite significant,” he said.

“There’s no question that once we used tenecteplase in lieu of tPA, it’s been just so much easier to administer and affects the interhospital transfer protocols, because you’re not transferring the patient with a critical care IV. It’s a win-win situation for everyone.”

The study received funding from the National Science and Technology Major Project, the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, and the China Shijiazhuang Pharmaceutical Company Recomgen Pharmaceutical (Guangzhou). Dr. Li, Dr. Goldstein, and Dr. Jovin report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Tenecteplase is as effective as alteplase with respect to disability outcomes and safety in Chinese patients with ischemic stroke, a new study has found. “This was a pivotal trial in establishing the safety and efficacy of tenecteplase as an alternative to alteplase in the thrombolytic treatment of acute ischemic stroke within 4.5 hours in Asian patients,” said study author Shuya Li, MD, associate chief physician, department of neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing.

The findings in this all-Chinese population should have an impact on the use of tenecteplase going forward, said Dr. Li. “The results provide further evidence to support a worldwide switch to tenecteplase as the preferred thrombolytic for acute ischemic stroke.”

The findings were presented at the 2023 International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
 

Single bolus

Use of alteplase (tissue plasminogen activator [tPA]) has for years been the main approach to thrombolytic reperfusion therapy for patients with acute stroke, but tenecteplase has recently emerged as a potential successor.

Tenecteplase is a tPA produced by recombinant DNA technology. It has a relatively long half-life and can be delivered in a single bolus instead of requiring an hour-long infusion, as is the case with alteplase.

The phase 3 noninferiority Tenecteplase Reperfusion Therapy in Acute ischemic Cerebrovascular Events (TRACE-2) trial – the first of its kind in an Asian population – included 1,430 adult ischemic stroke patients at 53 Chinese centers. Patients had to have a National Institutes of Health Stroke Scale (NIHSS) score of 5-25 and either not be eligible for or have refused endovascular therapy.

The mean age of study participants was about 66 years, and the percentage of women was about 31%. The mean baseline NIHSS score was 7 in both groups, and the symptom-onset-to-needle time was similar at 180 minutes for the tenecteplase group and 178.5 minutes for the alteplase group.

Researchers randomly assigned patients to receive tenecteplase or alteplase within 4.5 hours of symptom onset.

Those in the tenecteplase group received 0.25 mg/kg of the drug in a single IV bolus (maximum dose, 25 mg). Control group members who were treated with alteplase were given the drug as a 10% bolus, with the remainder given as a 1-hour infusion (0.9 mg/kg with a maximum dose of 90 mg).
 

Showed noninferiority

The primary efficacy outcome was a modified Rankins scale (mRS) score of 0-1 at 90 days, which is considered excellent function. About 62% of tenecteplase patients and 58% of alteplase patients attained this outcome (risk ratio, 1.09; 95% confidence interval, 1.00-1.18).

The P value was .001 for noninferiority and .06 for superiority, but Dr. Li explained that these values may change when considering the site effect.

There were no statistically significant differences between the two drugs on secondary outcomes of favorable function. For example, 73% of tenecteplase patients and 72% of alteplase patients had an mRS score of 0-2 at 3 months, and 50% in the tenecteplase and 49% in the alteplase group improved by 4 or more points on the NIHSS, or had a score of 1 or less, at 24 hours.

The groups also had comparable scores on the European quality-of-life visual analogue scale and on the Barthel index, which measures functional independence related to personal care and mobility.

Tenecteplase also turned out to be as safe at alteplase. About 2% in both groups had symptomatic intracranial hemorrhage within 36 hours, and both groups had that same percentage for such hemorrhages within 90 days. As well, the groups had a similar rate of any intracranial hemorrhage within 90 days (6% and 7%).

The mortality rate was 7% in the tenecteplase group, compared with 5% in the alteplase group.

Adverse events (AEs) occurred in 86% and 87%, and serious AEs in 16% and 15%, of the tenecteplase and alteplase groups, respectively, again with no statistically significant differences.

The research team aims to test the effectiveness of tenecteplase in other stroke patients, including those with minor strokes, those receiving thrombolysis in a later window, and those receiving endovascular therapy, said Dr. Li.
 

Strong evidence

Commenting on the study findings, Larry B. Goldstein, MD, professor and chair of neurology, University of Kentucky, Lexington, said it is important to determine the efficacy of tenecteplase among Asians, as they represent “an entirely different population” with unique concerns, such as bleeding complications from anticoagulants.

He noted an advantage of tenecteplase is ease of administration. “You don’t have to go through the loading dose and then the 1-hour infusion,” which poses an “additional hassle” when transferring patients between institutions, he said.

However, he noted that a possible “downside” to having both drugs available in the emergency department is “using the wrong drug at the wrong dose” because of their similar sounding names.

Also commenting on the study, Tudor G. Jovin, MD, professor and chair, department of neurology, Rowan University, Camden, N.J., said he welcomes another trial that confirms that these two drugs are biologically similar.

“I’m very glad this trial was done because it adds another very strong piece of evidence of equivalency.”

But the two drugs are not the same in some important respects, said Dr. Jovin, whose center switched to using tenecteplase almost 3 years ago. That switch has resulted in cutting 17 minutes from the door-to-needle time “which is quite significant,” he said.

“There’s no question that once we used tenecteplase in lieu of tPA, it’s been just so much easier to administer and affects the interhospital transfer protocols, because you’re not transferring the patient with a critical care IV. It’s a win-win situation for everyone.”

The study received funding from the National Science and Technology Major Project, the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, and the China Shijiazhuang Pharmaceutical Company Recomgen Pharmaceutical (Guangzhou). Dr. Li, Dr. Goldstein, and Dr. Jovin report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Performing endovascular thrombectomy in patients with an ischemic stroke having a large ischemic core has been found to be beneficial in a major international trial, which is expected to lead to a change in clinical practice and the way in which systems of stroke care are organized.

The results of the SELECT2 trial, which was conducted in sites in the United States, Canada, Europe, Australia, and New Zealand, showed that endovascular thrombectomy plus medical care resulted in better clinical outcomes than medical care alone in patients with a large ischemic core who presented within 24 hours after the time they were last known to be well.

The results of the SELECT2 trial were presented at the International Stroke Conference by Amrou Sarraj, MD. Dr. Sarraj is professor of neurology at University Hospitals Cleveland Medical Center–Case Western Reserve University in Ohio. The study was also simultaneously published online in the New England Journal of Medicine.

A similar trial conducted in China, the ANGEL-ASPECT trial, was also presented at the same ISC session and showed very similar results.

These two trials add to another Japanese study reported last year, the RESCUE-JAPAN LIMIT trial, also showing benefit of thrombectomy in patients with large core strokes.

Dr. Sarraj concluded that the results of these three trials together “unequivocally demonstrate the benefit of endovascular thrombectomy in patients with large ischemic core.”
 

A clear benefit

Approximately 20% of large-vessel occlusion strokes have a large core, but these patients have not been considered candidates for endovascular thrombectomy because of concerns about potential reperfusion injury in necrotic brain tissue, resulting in an increased risk of hemorrhage, edema, disability, and death.

This has resulted in uncertainty about how to manage these patients with a core infarct, Dr. Sarraj noted at the conference presented by the American Stroke Association, a division of the American Heart Association. 

The SELECT2 trial involved patients with stroke as a result of occlusion of the internal carotid artery or the first segment of the middle cerebral artery. Patients had a large ischemic core volume, defined as an ASPECTS (Alberta Stroke Program Early Computed Tomography Score) of 3-5, or a core volume of at least 50 mL on imaging. They were randomly assigned to endovascular thrombectomy plus medical care or to medical care alone.

The trial was aiming to enroll 560 patients but was stopped early for efficacy after 178 patients had been assigned to the thrombectomy group and 174 to the medical-care group.

The primary outcome – the generalized odds ratio for a shift in the distribution of modified Rankin scale scores toward better outcomes in favor of thrombectomy was 1.51 (P < .001).

“This translates into a 60% probability of achieving a better functional outcome in patients receiving thrombectomy, with a number needed to treat of five. That means five patients need to be treated with thrombectomy for one to achieve a better functional outcome,” Dr. Sarraj stated. 

The secondary outcome of functional independence at 90 days (a score on the modified Rankin scale of 0-2) occurred in 20% of the patients in the thrombectomy group and 7% in the medical-care group (relative risk, 2.97), with a number needed to treat of seven.

Independent ambulation (a score on the modified Rankin Scale of 0-3) at 90 days occurred in 37.9% of the patients in the thrombectomy group and in 18.7% of the patients in the medical-care group (relative risk, 2.06), with a number needed to treat of five.

Mortality was similar in the two groups.

The results for other secondary outcomes were generally in the same direction as those of the primary analysis, with the possible exception of early neurologic improvement, the authors reported.

The incidence of symptomatic intracranial hemorrhage was low in both trial groups, occurring in one patient in the thrombectomy group and two in the medical care group.

The investigators pointed out that previous studies have reported rates of symptomatic intracranial hemorrhage in patients with large ischemic core lesions that are higher than those in this trial. “Therefore, the low percentage of patients with symptomatic intracranial hemorrhage observed in both trial groups was unexpected.”

Approximately 20% of the patients in the thrombectomy group had complications associated with the procedure. In the thrombectomy group, arterial access-site complications occurred in 5 patients, dissection in 10, cerebral vessel perforation in 7, and transient vasospasm in 11.

Early neurologic worsening, defined as an increase of 4 or more points on the National Institutes of Health Stroke Scale (NIHSS), occurred in 24.7% in the thrombectomy group and in 15.5% in the medical-care group (relative risk, 1.59).

In a post-hoc analysis, “from which no conclusions can be drawn,” the authors reported,  early neurologic worsening was associated with worse functional outcomes at 90 days, and patients who had neurologic worsening had larger ischemic core lesions at baseline (median volume, 107 mL) versus 77 mL among patients without neurologic worsening.

They noted that a potential cause of deterioration in some of these patients was brain edema associated with reperfusion. However, they emphasize that overall, endovascular thrombectomy was associated with better outcomes than medical care alone.

“Two-thirds of patients had core infarct sizes more than 70 mL, and one-third of patients had core infarct sizes of more than 100 mL, but even in patients with large and very large core volumes, thrombectomy was superior to medical care alone,” Dr. Sarraj said.
 

This will ‘change practice’

In a comment, ISC 2023 chair Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., said: “This trial shows that even patients with a large core infarct who we would not have treated with thrombectomy in the past, actually do benefit from this procedure. And the surprise is that the benefit is nearly to the same extent as that in patients with smaller core infarcts. That is going to change practice.”

Dr. Jovin said that these results should not only change the selection of patients for thrombectomy, but they should also change systems of care. “Because the systems of care now are based around excluding these patients with large infarcts. We won’t need to do that in future.”

He elaborated: “I think imaging has held us back to be honest. We can exclude hemorrhage with a plain CT scan. Then after this, the biggest piece of information we need from imaging is the size of the infarct. We were concerned that we might hurt the patient if the infarct was large. Outside hospitals had to do advanced imaging before deciding whether to transfer patients for thrombectomy. These are all sources of delays.

“I am very pleased to see these results, and I hope to see a much more simplified triage of patients that will be more liberal to patients with the large infarcts,” he added.

Also commenting, Joseph Broderick, MD, professor of neurology and director of the Neuroscience Institute at the University of Cincinnati, said the results were “robust and important.” 

He said the results of the SELECT2 trial, along with the other two similar trials, “will change practice and extend endovascular therapy to more patients with severe strokes.”

But Dr. Broderick believes imaging will still be necessary to exclude patients with ASPECTS scores of 0-2, who were not included in these trials. “These are patients who have very large areas of clear hypodensity on the baseline image (brain already dying or dead). These patients do not benefit from reperfusion with lytic drugs or endovascular therapy,” he noted.
 

‘Welcome news’

In an editorial accompanying the print publication of the two new studies, Pierre Fayad, MD, University of Nebraska Medical Center, Omaha, points out that all three trials of thrombectomy in patients with large core infarct strokes “showed remarkably similar results” despite differences in design, patient selection, thrombolytic treatment and dose, geographic location, and imaging criteria.

“Together, the trials provide reassuring information from more than a thousand patients with large ischemic strokes in different medical systems that will probably lead to changes in patterns of care delivery.”

Dr. Fayad said it is reasonable to suggest that endovascular thrombectomy be offered to patients with large strokes if they arrive in a timely fashion at a center that is capable of performing the procedure, and if the patients have an ASPECTS value of 3-5 or an ischemic core volume of 50 mL or greater.

Higher rates of good outcomes may be anticipated if this treatment is performed, despite increased risks of symptomatic hemorrhage, edema, neurologic worsening, and hemicraniectomy, he noted.  

“Patients and families should be made aware of the limitations of treatment and the anticipated residual neurologic deficits resulting from the large infarction. The improved chance of independent walking and the ability to perform other daily activities in patients with the most severe strokes is welcome news for patients and for the field of stroke treatment,” he concluded.

The SELECT2 trial was supported by an investigator-initiated grant from Stryker Neurovascular to University Hospitals Cleveland Medical Center and the University of Texas McGovern Medical School.

A version of this article first appeared on Medscape.com.

Performing endovascular thrombectomy in patients with an ischemic stroke having a large ischemic core has been found to be beneficial in a major international trial, which is expected to lead to a change in clinical practice and the way in which systems of stroke care are organized.

The results of the SELECT2 trial, which was conducted in sites in the United States, Canada, Europe, Australia, and New Zealand, showed that endovascular thrombectomy plus medical care resulted in better clinical outcomes than medical care alone in patients with a large ischemic core who presented within 24 hours after the time they were last known to be well.

The results of the SELECT2 trial were presented at the International Stroke Conference by Amrou Sarraj, MD. Dr. Sarraj is professor of neurology at University Hospitals Cleveland Medical Center–Case Western Reserve University in Ohio. The study was also simultaneously published online in the New England Journal of Medicine.

A similar trial conducted in China, the ANGEL-ASPECT trial, was also presented at the same ISC session and showed very similar results.

These two trials add to another Japanese study reported last year, the RESCUE-JAPAN LIMIT trial, also showing benefit of thrombectomy in patients with large core strokes.

Dr. Sarraj concluded that the results of these three trials together “unequivocally demonstrate the benefit of endovascular thrombectomy in patients with large ischemic core.”
 

A clear benefit

Approximately 20% of large-vessel occlusion strokes have a large core, but these patients have not been considered candidates for endovascular thrombectomy because of concerns about potential reperfusion injury in necrotic brain tissue, resulting in an increased risk of hemorrhage, edema, disability, and death.

This has resulted in uncertainty about how to manage these patients with a core infarct, Dr. Sarraj noted at the conference presented by the American Stroke Association, a division of the American Heart Association. 

The SELECT2 trial involved patients with stroke as a result of occlusion of the internal carotid artery or the first segment of the middle cerebral artery. Patients had a large ischemic core volume, defined as an ASPECTS (Alberta Stroke Program Early Computed Tomography Score) of 3-5, or a core volume of at least 50 mL on imaging. They were randomly assigned to endovascular thrombectomy plus medical care or to medical care alone.

The trial was aiming to enroll 560 patients but was stopped early for efficacy after 178 patients had been assigned to the thrombectomy group and 174 to the medical-care group.

The primary outcome – the generalized odds ratio for a shift in the distribution of modified Rankin scale scores toward better outcomes in favor of thrombectomy was 1.51 (P < .001).

“This translates into a 60% probability of achieving a better functional outcome in patients receiving thrombectomy, with a number needed to treat of five. That means five patients need to be treated with thrombectomy for one to achieve a better functional outcome,” Dr. Sarraj stated. 

The secondary outcome of functional independence at 90 days (a score on the modified Rankin scale of 0-2) occurred in 20% of the patients in the thrombectomy group and 7% in the medical-care group (relative risk, 2.97), with a number needed to treat of seven.

Independent ambulation (a score on the modified Rankin Scale of 0-3) at 90 days occurred in 37.9% of the patients in the thrombectomy group and in 18.7% of the patients in the medical-care group (relative risk, 2.06), with a number needed to treat of five.

Mortality was similar in the two groups.

The results for other secondary outcomes were generally in the same direction as those of the primary analysis, with the possible exception of early neurologic improvement, the authors reported.

The incidence of symptomatic intracranial hemorrhage was low in both trial groups, occurring in one patient in the thrombectomy group and two in the medical care group.

The investigators pointed out that previous studies have reported rates of symptomatic intracranial hemorrhage in patients with large ischemic core lesions that are higher than those in this trial. “Therefore, the low percentage of patients with symptomatic intracranial hemorrhage observed in both trial groups was unexpected.”

Approximately 20% of the patients in the thrombectomy group had complications associated with the procedure. In the thrombectomy group, arterial access-site complications occurred in 5 patients, dissection in 10, cerebral vessel perforation in 7, and transient vasospasm in 11.

Early neurologic worsening, defined as an increase of 4 or more points on the National Institutes of Health Stroke Scale (NIHSS), occurred in 24.7% in the thrombectomy group and in 15.5% in the medical-care group (relative risk, 1.59).

In a post-hoc analysis, “from which no conclusions can be drawn,” the authors reported,  early neurologic worsening was associated with worse functional outcomes at 90 days, and patients who had neurologic worsening had larger ischemic core lesions at baseline (median volume, 107 mL) versus 77 mL among patients without neurologic worsening.

They noted that a potential cause of deterioration in some of these patients was brain edema associated with reperfusion. However, they emphasize that overall, endovascular thrombectomy was associated with better outcomes than medical care alone.

“Two-thirds of patients had core infarct sizes more than 70 mL, and one-third of patients had core infarct sizes of more than 100 mL, but even in patients with large and very large core volumes, thrombectomy was superior to medical care alone,” Dr. Sarraj said.
 

This will ‘change practice’

In a comment, ISC 2023 chair Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., said: “This trial shows that even patients with a large core infarct who we would not have treated with thrombectomy in the past, actually do benefit from this procedure. And the surprise is that the benefit is nearly to the same extent as that in patients with smaller core infarcts. That is going to change practice.”

Dr. Jovin said that these results should not only change the selection of patients for thrombectomy, but they should also change systems of care. “Because the systems of care now are based around excluding these patients with large infarcts. We won’t need to do that in future.”

He elaborated: “I think imaging has held us back to be honest. We can exclude hemorrhage with a plain CT scan. Then after this, the biggest piece of information we need from imaging is the size of the infarct. We were concerned that we might hurt the patient if the infarct was large. Outside hospitals had to do advanced imaging before deciding whether to transfer patients for thrombectomy. These are all sources of delays.

“I am very pleased to see these results, and I hope to see a much more simplified triage of patients that will be more liberal to patients with the large infarcts,” he added.

Also commenting, Joseph Broderick, MD, professor of neurology and director of the Neuroscience Institute at the University of Cincinnati, said the results were “robust and important.” 

He said the results of the SELECT2 trial, along with the other two similar trials, “will change practice and extend endovascular therapy to more patients with severe strokes.”

But Dr. Broderick believes imaging will still be necessary to exclude patients with ASPECTS scores of 0-2, who were not included in these trials. “These are patients who have very large areas of clear hypodensity on the baseline image (brain already dying or dead). These patients do not benefit from reperfusion with lytic drugs or endovascular therapy,” he noted.
 

‘Welcome news’

In an editorial accompanying the print publication of the two new studies, Pierre Fayad, MD, University of Nebraska Medical Center, Omaha, points out that all three trials of thrombectomy in patients with large core infarct strokes “showed remarkably similar results” despite differences in design, patient selection, thrombolytic treatment and dose, geographic location, and imaging criteria.

“Together, the trials provide reassuring information from more than a thousand patients with large ischemic strokes in different medical systems that will probably lead to changes in patterns of care delivery.”

Dr. Fayad said it is reasonable to suggest that endovascular thrombectomy be offered to patients with large strokes if they arrive in a timely fashion at a center that is capable of performing the procedure, and if the patients have an ASPECTS value of 3-5 or an ischemic core volume of 50 mL or greater.

Higher rates of good outcomes may be anticipated if this treatment is performed, despite increased risks of symptomatic hemorrhage, edema, neurologic worsening, and hemicraniectomy, he noted.  

“Patients and families should be made aware of the limitations of treatment and the anticipated residual neurologic deficits resulting from the large infarction. The improved chance of independent walking and the ability to perform other daily activities in patients with the most severe strokes is welcome news for patients and for the field of stroke treatment,” he concluded.

The SELECT2 trial was supported by an investigator-initiated grant from Stryker Neurovascular to University Hospitals Cleveland Medical Center and the University of Texas McGovern Medical School.

A version of this article first appeared on Medscape.com.

Performing endovascular thrombectomy in patients with an ischemic stroke having a large ischemic core has been found to be beneficial in a major international trial, which is expected to lead to a change in clinical practice and the way in which systems of stroke care are organized.

The results of the SELECT2 trial, which was conducted in sites in the United States, Canada, Europe, Australia, and New Zealand, showed that endovascular thrombectomy plus medical care resulted in better clinical outcomes than medical care alone in patients with a large ischemic core who presented within 24 hours after the time they were last known to be well.

The results of the SELECT2 trial were presented at the International Stroke Conference by Amrou Sarraj, MD. Dr. Sarraj is professor of neurology at University Hospitals Cleveland Medical Center–Case Western Reserve University in Ohio. The study was also simultaneously published online in the New England Journal of Medicine.

A similar trial conducted in China, the ANGEL-ASPECT trial, was also presented at the same ISC session and showed very similar results.

These two trials add to another Japanese study reported last year, the RESCUE-JAPAN LIMIT trial, also showing benefit of thrombectomy in patients with large core strokes.

Dr. Sarraj concluded that the results of these three trials together “unequivocally demonstrate the benefit of endovascular thrombectomy in patients with large ischemic core.”
 

A clear benefit

Approximately 20% of large-vessel occlusion strokes have a large core, but these patients have not been considered candidates for endovascular thrombectomy because of concerns about potential reperfusion injury in necrotic brain tissue, resulting in an increased risk of hemorrhage, edema, disability, and death.

This has resulted in uncertainty about how to manage these patients with a core infarct, Dr. Sarraj noted at the conference presented by the American Stroke Association, a division of the American Heart Association. 

The SELECT2 trial involved patients with stroke as a result of occlusion of the internal carotid artery or the first segment of the middle cerebral artery. Patients had a large ischemic core volume, defined as an ASPECTS (Alberta Stroke Program Early Computed Tomography Score) of 3-5, or a core volume of at least 50 mL on imaging. They were randomly assigned to endovascular thrombectomy plus medical care or to medical care alone.

The trial was aiming to enroll 560 patients but was stopped early for efficacy after 178 patients had been assigned to the thrombectomy group and 174 to the medical-care group.

The primary outcome – the generalized odds ratio for a shift in the distribution of modified Rankin scale scores toward better outcomes in favor of thrombectomy was 1.51 (P < .001).

“This translates into a 60% probability of achieving a better functional outcome in patients receiving thrombectomy, with a number needed to treat of five. That means five patients need to be treated with thrombectomy for one to achieve a better functional outcome,” Dr. Sarraj stated. 

The secondary outcome of functional independence at 90 days (a score on the modified Rankin scale of 0-2) occurred in 20% of the patients in the thrombectomy group and 7% in the medical-care group (relative risk, 2.97), with a number needed to treat of seven.

Independent ambulation (a score on the modified Rankin Scale of 0-3) at 90 days occurred in 37.9% of the patients in the thrombectomy group and in 18.7% of the patients in the medical-care group (relative risk, 2.06), with a number needed to treat of five.

Mortality was similar in the two groups.

The results for other secondary outcomes were generally in the same direction as those of the primary analysis, with the possible exception of early neurologic improvement, the authors reported.

The incidence of symptomatic intracranial hemorrhage was low in both trial groups, occurring in one patient in the thrombectomy group and two in the medical care group.

The investigators pointed out that previous studies have reported rates of symptomatic intracranial hemorrhage in patients with large ischemic core lesions that are higher than those in this trial. “Therefore, the low percentage of patients with symptomatic intracranial hemorrhage observed in both trial groups was unexpected.”

Approximately 20% of the patients in the thrombectomy group had complications associated with the procedure. In the thrombectomy group, arterial access-site complications occurred in 5 patients, dissection in 10, cerebral vessel perforation in 7, and transient vasospasm in 11.

Early neurologic worsening, defined as an increase of 4 or more points on the National Institutes of Health Stroke Scale (NIHSS), occurred in 24.7% in the thrombectomy group and in 15.5% in the medical-care group (relative risk, 1.59).

In a post-hoc analysis, “from which no conclusions can be drawn,” the authors reported,  early neurologic worsening was associated with worse functional outcomes at 90 days, and patients who had neurologic worsening had larger ischemic core lesions at baseline (median volume, 107 mL) versus 77 mL among patients without neurologic worsening.

They noted that a potential cause of deterioration in some of these patients was brain edema associated with reperfusion. However, they emphasize that overall, endovascular thrombectomy was associated with better outcomes than medical care alone.

“Two-thirds of patients had core infarct sizes more than 70 mL, and one-third of patients had core infarct sizes of more than 100 mL, but even in patients with large and very large core volumes, thrombectomy was superior to medical care alone,” Dr. Sarraj said.
 

This will ‘change practice’

In a comment, ISC 2023 chair Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., said: “This trial shows that even patients with a large core infarct who we would not have treated with thrombectomy in the past, actually do benefit from this procedure. And the surprise is that the benefit is nearly to the same extent as that in patients with smaller core infarcts. That is going to change practice.”

Dr. Jovin said that these results should not only change the selection of patients for thrombectomy, but they should also change systems of care. “Because the systems of care now are based around excluding these patients with large infarcts. We won’t need to do that in future.”

He elaborated: “I think imaging has held us back to be honest. We can exclude hemorrhage with a plain CT scan. Then after this, the biggest piece of information we need from imaging is the size of the infarct. We were concerned that we might hurt the patient if the infarct was large. Outside hospitals had to do advanced imaging before deciding whether to transfer patients for thrombectomy. These are all sources of delays.

“I am very pleased to see these results, and I hope to see a much more simplified triage of patients that will be more liberal to patients with the large infarcts,” he added.

Also commenting, Joseph Broderick, MD, professor of neurology and director of the Neuroscience Institute at the University of Cincinnati, said the results were “robust and important.” 

He said the results of the SELECT2 trial, along with the other two similar trials, “will change practice and extend endovascular therapy to more patients with severe strokes.”

But Dr. Broderick believes imaging will still be necessary to exclude patients with ASPECTS scores of 0-2, who were not included in these trials. “These are patients who have very large areas of clear hypodensity on the baseline image (brain already dying or dead). These patients do not benefit from reperfusion with lytic drugs or endovascular therapy,” he noted.
 

‘Welcome news’

In an editorial accompanying the print publication of the two new studies, Pierre Fayad, MD, University of Nebraska Medical Center, Omaha, points out that all three trials of thrombectomy in patients with large core infarct strokes “showed remarkably similar results” despite differences in design, patient selection, thrombolytic treatment and dose, geographic location, and imaging criteria.

“Together, the trials provide reassuring information from more than a thousand patients with large ischemic strokes in different medical systems that will probably lead to changes in patterns of care delivery.”

Dr. Fayad said it is reasonable to suggest that endovascular thrombectomy be offered to patients with large strokes if they arrive in a timely fashion at a center that is capable of performing the procedure, and if the patients have an ASPECTS value of 3-5 or an ischemic core volume of 50 mL or greater.

Higher rates of good outcomes may be anticipated if this treatment is performed, despite increased risks of symptomatic hemorrhage, edema, neurologic worsening, and hemicraniectomy, he noted.  

“Patients and families should be made aware of the limitations of treatment and the anticipated residual neurologic deficits resulting from the large infarction. The improved chance of independent walking and the ability to perform other daily activities in patients with the most severe strokes is welcome news for patients and for the field of stroke treatment,” he concluded.

The SELECT2 trial was supported by an investigator-initiated grant from Stryker Neurovascular to University Hospitals Cleveland Medical Center and the University of Texas McGovern Medical School.

A version of this article first appeared on Medscape.com.

Artificially lowering blood pressure in stroke patients following endovascular therapy is not necessarily a good strategy, new research suggests. Preliminary results of a new study showed that using an antihypertensive drug to target systolic blood pressure to below 160 mm Hg or 140 mm Hg in these patients may not be beneficial, and may even be harmful.

“This line of inquiry is probably not worth pursuing,” said stroke neurologist Eva A. Mistry, MBBS, MSCI, assistant professor of clinical neurology and rehabilitation medicine, University of Cincinnati.

Following current blood pressure guidelines in these patients (so targeting blood pressure under 180/105 mm Hg) “is probably reasonable,” unless the patient’s systolic blood pressure goes above 180, Dr. Mistry said. “Artificially trying to lower it may result in harm, at least in terms of the disability outcome.”

The findings were presented at the 2023 International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

Endovascular therapy has become standard of care for patients with large vessel occlusion after studies showed “massive benefit,” yet about 50% of patients remain disabled or die at 90 days, Dr. Mistry said.

“We have been on the quest to understand if there’s something we can do to improve these outcomes.”

One approach could be optimizing medical management. Previous observational studies showed that higher blood pressure values after thrombectomy are associated with worse outcomes.
 

Taking it forward

“We wanted to take that forward in a randomized inquiry to see first with this trial if [artificially] lowering blood pressure using medications is safe, and preliminarily understand if it could be efficacious in a larger trial,” she said.

This blood pressure–lowering strategy is already practiced in some centers. A nationwide survey conducted by Dr. Mistry and her colleagues showed a wide range of targets, with some institutions aiming it as low as under 120 mm Hg after thrombectomy, which she found “surprising.”

The Blood pressure after Endovascular Stroke Treatment-II (BEST-II) study included 120 ischemic stroke patients at three stroke centers, mean age 70 years and 57% female, who had undergone endovascular treatment. They were randomized to one of three target blood pressure groups: 180 mm Hg or under, less than 160 mm Hg, or under 140 mm Hg.

To lower blood pressure, researchers used intravenous nicardipine, a calcium channel blocker, as a first line. This was started within 1 hour of the endovascular treatment and given for 24 hours if the patient’s systolic blood pressure was above the target of their group.

In the highest target group (≤180 mm Hg), the average systolic blood pressure reached 129 mm Hg. In the middle target group (<160 mm Hg), the average systolic blood pressure was 131 mm Hg, and in the lowest target group (<140 mm Hg), systolic blood pressure was lowered to an average of 123 mm Hg.
 

Mean infarct volumes

At 36 hours, the mean adjusted infarct volume was slightly lower in the lowest blood pressure target group (32.4), compared with the other groups (46.4 for the 180 mm Hg group and 50.7 for the under-160 mm Hg group).

“Based on a model or a slope that would be associated with serial lowering of blood pressure targets, we found the point estimate of the effect size was slightly in the direction of benefit of lower blood pressure targets in terms of lower infarct volume,” Dr. Mistry said.

But this was not conclusive. While the point estimate was in the direction of benefit, Dr. Mistry stressed that the trial design doesn’t “definitely rule out” the possibility of harm.

Researchers also measured functional status at 90 days with the modified Rankin Scale (mRS). They found that the utility-weighted mRS was slightly lower in the lowest blood pressure target group (0.507), compared with the higher target groups (0.584 and 0.475, respectively, for the 180 mm Hg and under-160 mm Hg groups).

“The effect size was slightly in the direction of harm,” Dr. Mistry said. “To me, that means there might be safety issues associated with the lower blood pressure target.”
 

Probably futile

The results suggest that studying this issue further is probably futile. “If lowering blood pressure improves outcomes, that improvement is fairly marginal, and there are trends that suggest that, in fact, it might be harmful,” Dr. Mistry said. Her researcher team “believes it would not be the wisest decision” to pursue this strategy any further in a phase 3 study, she said.

“We wanted to understand whether or not we should spend millions of dollars to do a thousand-patient or two thousand-patient trial, and the answer to that is probably not.”

And there are other therapeutics “we can test that might be more promising than this approach,” she added.

In the meantime, Dr. Mistry stressed that clinicians should be cautious about automatically lowering blood pressure in this patient population and that decisions to target lower levels should be done on an individual basis.
 

Timely and important

In a comment, Karen Furie, MD, MPH, chair of neurology, Brown University, Providence, R.I., said that the study is “timely and important,” given the uncertainty about management of blood pressure after opening the vessel again using endovascular treatment.

“We already knew that letting the blood pressure go very high after reperfusion was bad, and this study shows that lowering it may also pose a risk, and I think that’s an important message for the community.”

The results send a cautionary message to clinicians but do not provide definitive evidence, she added. “Perhaps in the future we will have a better understanding of what the optimal range is.”

Dr. Furie stressed that this was a small pilot study and conclusions are “guarded.”

“I think the authors didn’t want to overinterpret the results so they ended up concluding that because the final disability might have been worse in the patients who had their blood pressure significantly lowered, recommending that as an approach across the board is sort of discouraged.”

Instead, the authors indicated that there may be factors such as degree of recanalization, size of the infarct, or other patient-specific factors “that would dictate where you target blood pressures,” Dr. Furie said.

The study was funded by the National Institutes of Health/National Institute of Neurological Disorders and Stroke. Mistry receives funding from the Patient-Centered Outcomes Research Institute and compensation from the American Heart Association for editorial activities, and is a consultant for RapidAI. Dr. Furie has declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Artificially lowering blood pressure in stroke patients following endovascular therapy is not necessarily a good strategy, new research suggests. Preliminary results of a new study showed that using an antihypertensive drug to target systolic blood pressure to below 160 mm Hg or 140 mm Hg in these patients may not be beneficial, and may even be harmful.

“This line of inquiry is probably not worth pursuing,” said stroke neurologist Eva A. Mistry, MBBS, MSCI, assistant professor of clinical neurology and rehabilitation medicine, University of Cincinnati.

Following current blood pressure guidelines in these patients (so targeting blood pressure under 180/105 mm Hg) “is probably reasonable,” unless the patient’s systolic blood pressure goes above 180, Dr. Mistry said. “Artificially trying to lower it may result in harm, at least in terms of the disability outcome.”

The findings were presented at the 2023 International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

Endovascular therapy has become standard of care for patients with large vessel occlusion after studies showed “massive benefit,” yet about 50% of patients remain disabled or die at 90 days, Dr. Mistry said.

“We have been on the quest to understand if there’s something we can do to improve these outcomes.”

One approach could be optimizing medical management. Previous observational studies showed that higher blood pressure values after thrombectomy are associated with worse outcomes.
 

Taking it forward

“We wanted to take that forward in a randomized inquiry to see first with this trial if [artificially] lowering blood pressure using medications is safe, and preliminarily understand if it could be efficacious in a larger trial,” she said.

This blood pressure–lowering strategy is already practiced in some centers. A nationwide survey conducted by Dr. Mistry and her colleagues showed a wide range of targets, with some institutions aiming it as low as under 120 mm Hg after thrombectomy, which she found “surprising.”

The Blood pressure after Endovascular Stroke Treatment-II (BEST-II) study included 120 ischemic stroke patients at three stroke centers, mean age 70 years and 57% female, who had undergone endovascular treatment. They were randomized to one of three target blood pressure groups: 180 mm Hg or under, less than 160 mm Hg, or under 140 mm Hg.

To lower blood pressure, researchers used intravenous nicardipine, a calcium channel blocker, as a first line. This was started within 1 hour of the endovascular treatment and given for 24 hours if the patient’s systolic blood pressure was above the target of their group.

In the highest target group (≤180 mm Hg), the average systolic blood pressure reached 129 mm Hg. In the middle target group (<160 mm Hg), the average systolic blood pressure was 131 mm Hg, and in the lowest target group (<140 mm Hg), systolic blood pressure was lowered to an average of 123 mm Hg.
 

Mean infarct volumes

At 36 hours, the mean adjusted infarct volume was slightly lower in the lowest blood pressure target group (32.4), compared with the other groups (46.4 for the 180 mm Hg group and 50.7 for the under-160 mm Hg group).

“Based on a model or a slope that would be associated with serial lowering of blood pressure targets, we found the point estimate of the effect size was slightly in the direction of benefit of lower blood pressure targets in terms of lower infarct volume,” Dr. Mistry said.

But this was not conclusive. While the point estimate was in the direction of benefit, Dr. Mistry stressed that the trial design doesn’t “definitely rule out” the possibility of harm.

Researchers also measured functional status at 90 days with the modified Rankin Scale (mRS). They found that the utility-weighted mRS was slightly lower in the lowest blood pressure target group (0.507), compared with the higher target groups (0.584 and 0.475, respectively, for the 180 mm Hg and under-160 mm Hg groups).

“The effect size was slightly in the direction of harm,” Dr. Mistry said. “To me, that means there might be safety issues associated with the lower blood pressure target.”
 

Probably futile

The results suggest that studying this issue further is probably futile. “If lowering blood pressure improves outcomes, that improvement is fairly marginal, and there are trends that suggest that, in fact, it might be harmful,” Dr. Mistry said. Her researcher team “believes it would not be the wisest decision” to pursue this strategy any further in a phase 3 study, she said.

“We wanted to understand whether or not we should spend millions of dollars to do a thousand-patient or two thousand-patient trial, and the answer to that is probably not.”

And there are other therapeutics “we can test that might be more promising than this approach,” she added.

In the meantime, Dr. Mistry stressed that clinicians should be cautious about automatically lowering blood pressure in this patient population and that decisions to target lower levels should be done on an individual basis.
 

Timely and important

In a comment, Karen Furie, MD, MPH, chair of neurology, Brown University, Providence, R.I., said that the study is “timely and important,” given the uncertainty about management of blood pressure after opening the vessel again using endovascular treatment.

“We already knew that letting the blood pressure go very high after reperfusion was bad, and this study shows that lowering it may also pose a risk, and I think that’s an important message for the community.”

The results send a cautionary message to clinicians but do not provide definitive evidence, she added. “Perhaps in the future we will have a better understanding of what the optimal range is.”

Dr. Furie stressed that this was a small pilot study and conclusions are “guarded.”

“I think the authors didn’t want to overinterpret the results so they ended up concluding that because the final disability might have been worse in the patients who had their blood pressure significantly lowered, recommending that as an approach across the board is sort of discouraged.”

Instead, the authors indicated that there may be factors such as degree of recanalization, size of the infarct, or other patient-specific factors “that would dictate where you target blood pressures,” Dr. Furie said.

The study was funded by the National Institutes of Health/National Institute of Neurological Disorders and Stroke. Mistry receives funding from the Patient-Centered Outcomes Research Institute and compensation from the American Heart Association for editorial activities, and is a consultant for RapidAI. Dr. Furie has declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Artificially lowering blood pressure in stroke patients following endovascular therapy is not necessarily a good strategy, new research suggests. Preliminary results of a new study showed that using an antihypertensive drug to target systolic blood pressure to below 160 mm Hg or 140 mm Hg in these patients may not be beneficial, and may even be harmful.

“This line of inquiry is probably not worth pursuing,” said stroke neurologist Eva A. Mistry, MBBS, MSCI, assistant professor of clinical neurology and rehabilitation medicine, University of Cincinnati.

Following current blood pressure guidelines in these patients (so targeting blood pressure under 180/105 mm Hg) “is probably reasonable,” unless the patient’s systolic blood pressure goes above 180, Dr. Mistry said. “Artificially trying to lower it may result in harm, at least in terms of the disability outcome.”

The findings were presented at the 2023 International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

Endovascular therapy has become standard of care for patients with large vessel occlusion after studies showed “massive benefit,” yet about 50% of patients remain disabled or die at 90 days, Dr. Mistry said.

“We have been on the quest to understand if there’s something we can do to improve these outcomes.”

One approach could be optimizing medical management. Previous observational studies showed that higher blood pressure values after thrombectomy are associated with worse outcomes.
 

Taking it forward

“We wanted to take that forward in a randomized inquiry to see first with this trial if [artificially] lowering blood pressure using medications is safe, and preliminarily understand if it could be efficacious in a larger trial,” she said.

This blood pressure–lowering strategy is already practiced in some centers. A nationwide survey conducted by Dr. Mistry and her colleagues showed a wide range of targets, with some institutions aiming it as low as under 120 mm Hg after thrombectomy, which she found “surprising.”

The Blood pressure after Endovascular Stroke Treatment-II (BEST-II) study included 120 ischemic stroke patients at three stroke centers, mean age 70 years and 57% female, who had undergone endovascular treatment. They were randomized to one of three target blood pressure groups: 180 mm Hg or under, less than 160 mm Hg, or under 140 mm Hg.

To lower blood pressure, researchers used intravenous nicardipine, a calcium channel blocker, as a first line. This was started within 1 hour of the endovascular treatment and given for 24 hours if the patient’s systolic blood pressure was above the target of their group.

In the highest target group (≤180 mm Hg), the average systolic blood pressure reached 129 mm Hg. In the middle target group (<160 mm Hg), the average systolic blood pressure was 131 mm Hg, and in the lowest target group (<140 mm Hg), systolic blood pressure was lowered to an average of 123 mm Hg.
 

Mean infarct volumes

At 36 hours, the mean adjusted infarct volume was slightly lower in the lowest blood pressure target group (32.4), compared with the other groups (46.4 for the 180 mm Hg group and 50.7 for the under-160 mm Hg group).

“Based on a model or a slope that would be associated with serial lowering of blood pressure targets, we found the point estimate of the effect size was slightly in the direction of benefit of lower blood pressure targets in terms of lower infarct volume,” Dr. Mistry said.

But this was not conclusive. While the point estimate was in the direction of benefit, Dr. Mistry stressed that the trial design doesn’t “definitely rule out” the possibility of harm.

Researchers also measured functional status at 90 days with the modified Rankin Scale (mRS). They found that the utility-weighted mRS was slightly lower in the lowest blood pressure target group (0.507), compared with the higher target groups (0.584 and 0.475, respectively, for the 180 mm Hg and under-160 mm Hg groups).

“The effect size was slightly in the direction of harm,” Dr. Mistry said. “To me, that means there might be safety issues associated with the lower blood pressure target.”
 

Probably futile

The results suggest that studying this issue further is probably futile. “If lowering blood pressure improves outcomes, that improvement is fairly marginal, and there are trends that suggest that, in fact, it might be harmful,” Dr. Mistry said. Her researcher team “believes it would not be the wisest decision” to pursue this strategy any further in a phase 3 study, she said.

“We wanted to understand whether or not we should spend millions of dollars to do a thousand-patient or two thousand-patient trial, and the answer to that is probably not.”

And there are other therapeutics “we can test that might be more promising than this approach,” she added.

In the meantime, Dr. Mistry stressed that clinicians should be cautious about automatically lowering blood pressure in this patient population and that decisions to target lower levels should be done on an individual basis.
 

Timely and important

In a comment, Karen Furie, MD, MPH, chair of neurology, Brown University, Providence, R.I., said that the study is “timely and important,” given the uncertainty about management of blood pressure after opening the vessel again using endovascular treatment.

“We already knew that letting the blood pressure go very high after reperfusion was bad, and this study shows that lowering it may also pose a risk, and I think that’s an important message for the community.”

The results send a cautionary message to clinicians but do not provide definitive evidence, she added. “Perhaps in the future we will have a better understanding of what the optimal range is.”

Dr. Furie stressed that this was a small pilot study and conclusions are “guarded.”

“I think the authors didn’t want to overinterpret the results so they ended up concluding that because the final disability might have been worse in the patients who had their blood pressure significantly lowered, recommending that as an approach across the board is sort of discouraged.”

Instead, the authors indicated that there may be factors such as degree of recanalization, size of the infarct, or other patient-specific factors “that would dictate where you target blood pressures,” Dr. Furie said.

The study was funded by the National Institutes of Health/National Institute of Neurological Disorders and Stroke. Mistry receives funding from the Patient-Centered Outcomes Research Institute and compensation from the American Heart Association for editorial activities, and is a consultant for RapidAI. Dr. Furie has declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In the STROKE AF study, among patients who had a stroke presumably caused by atherosclerosis, the rate of atrial fibrillation (AFib) was almost 22% at 3 years, as detected by continuous monitoring.

The 3-year results from the study were presented by Lee H. Schwamm, MD, of Massachusetts General Hospital, Boston, at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

Dr. Schwamm said the high rate of AFib detection in this study suggests that continuous monitoring for AFib should be considered for a larger population of stroke patients, rather than just those with cryptogenic stroke.

“We found a much higher rate of AF[ib] than we expected in this population of patients who have had an atherosclerotic stroke,” Dr. Schwamm said in an interview.

“These AF[ib] occurrences were found by a device, so they are known as ‘device-documented AF[ib].’ The patient is not generally aware of symptoms, but 67% of the AF[ib] episodes lasted for more than 1 hour, showing that this is not trivial AF[ib]. This is meaningful AF[ib],” he said.

Dr. Schwamm said the major question is whether these cases of AFib that are detected with a device warrant treatment with anticoagulation. He noted that, in this study, clinicians decided to provide anticoagulation to 70%-80% of patients in whom AFib was detected.

“If we think it deserves treatment, then we have to look for it. And if we care about finding AF[ib], we have no choice but to monitor continuously,” he said.

“If this data doesn’t convince you that AF[ib] is present in this population, I don’t think any data will. Because it is consistent, it accumulates over time and looks remarkably similar to a set of data that we have all become very comfortable with – the CRYSTAL-AF study in patients with cryptogenic stroke,” he stated.

Dr. Schwamm noted that the STROKE AF trial was not based on the cause of the index stroke; rather, it was asking whether there are risk factors that could contribute to the 25% stroke recurrence rate in this population that are not covered in current guidelines.

“I’m really trying to move away from the anchor that I was trained in, which is to figure out the cause of the last stroke to help decide how to prevent the next stroke, towards more of a probabilistic model – of what is all the information I have at my disposal and how do I act on it to prevent the next stroke? We have to start thinking differently about building models for future stroke risk and determining therapy based on that,” he commented.
 

Changing practice

ISC 2023 program chair Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., and moderator of the session at which the results were presented, discussed the STROKE AF results in a highlights presentation.

“To me as clinician, these results are even more relevant than those at 12 months,” Dr. Jovin said. “The lesson I took is that AF[ib] is even more prevalent than we thought. The burden of AF[ib] is significant in these patients, and it doesn’t seem to be limited to a particular time. These are very thought-provoking results which are going to change clinical practice. I think the threshold for long-term monitoring will be lower.”

Comoderator Lauren Sansing, MD, Yale University, New Haven, Conn., added: “This study shows that the longer we monitor, the more patients with AF[ib] we are likely to pick up. And because in two-thirds of patients with AF[ib], it lasted longer than 1 hour, I do believe this was clinically relevant AF[ib]. The question now is, do we monitor everyone? I think it puts the burden on us to search for AF[ib] in our patients.”

In his presentation, Dr. Schwamm explained that, on the basis of the CRYSTAL-AF study, insertable cardiac monitoring devices are frequently used to identify poststroke AFib in patients with cryptogenic stroke. In the device-monitored arm of that study, AFib was detected in 12.4% of patients over 12 months versus 2.0% in the control arm.

“However, we don’t know how often AF[ib] is detected in other presumed stroke types – largely those due to atherosclerosis,” he said.

He pointed out that, at present, long-term monitoring post stroke for the detection of AFib is not currently recommended for patients with ischemic stroke, owing to presumed small-vessel occlusion or large-artery atherosclerosis.

“In these patients, we are not suspecting AF[ib] because we believe the cause of the stroke was not embolic. But we wanted to investigate what the AF[ib] risk is in these patients, who often have multiple stroke risk factors,” he said.

The trial enrolled 496 patients at 33 centers in the United States. Eligible patients were aged 60 years or older or aged 50-59 years with at least one additional stroke risk factor and had an index stroke that was attributed to large-artery or small-vessel disease. Patients were randomly assigned either to continuous monitoring with the Reveal LINQ device (Medtronic) or to the control arm following site-specific standard of care for AFib detection.

Dr. Schwamm noted that usual care for these patients normally involves monitoring for just a few days while in hospital, but this picks up less than 5% of AFib occurrences.

Baseline characteristics of patients in the STROKE AF study showed that the enrolled population was at high risk for stroke, with a CHADSVASC score of 5. But the index strokes were generally small; the median National Institutes of Health Stroke Scale score was 2.

Results at 12 months, reported 2 years ago, showed a 12.5% incidence of AFib with continuous monitoring versus 1.8% with standard of care (hazard ratio, 7.7; P < .001), rates similar to that found in the CRYSTAL-AF study.

By 3 years, the rate of detected AFib had risen to 21.7% in the continuous monitoring arm versus 2.4% in the control arm (HR, 10.0; P < .001).

“At 12 months, we were seven times more likely to detect AF[ib] with continuous monitoring in these patients, and by 3 years, it was 10 times more likely that AF would be detected with continuous monitoring. I think we’ve settled the question of the best way to find AF[ib] in these patients – it is with an inserted device,” Dr. Schwamm said.

“We have also shown that this is not a transient rise in AFib after the stroke which then diminishes over the next few years. It is a continuous and progressive detection of AF[ib].”

Dr. Schwamm pointed out that 88% of the recorded AFib episodes were asymptomatic. “So relying on patients self-reporting symptoms when deciding who to monitor is unreliable and not a sensible strategy.”

The median time to the first adjudicated AFib episode at 12-month follow-up was 99 days; at the 3-year follow-up, it was 284 days.

“This shows that 30 days of monitoring with an external patch is not sufficient to exclude the presence of AF[ib]. And this really argues for a strategy of immediate insertion of cardiac monitor placement if your goal is to look for AF[ib],” Dr. Schwamm commented.
 

Is this clinically relevant AFib?

Dr. Schwamm acknowledged that there is a question of whether device-detected AFib should be thought about in the same way as clinically detected AFib with respect to future stroke risk.

He noted that, in this study, 67.4% of patients for whom AFib was detected by continuous monitoring (31 of 46 patients) had at least one episode of AFib that lasted more than 1 hour.

“This is not a trivial little squiggle of something on an EKG which then goes away. This is of significant duration that the cardiologist who adjudicated these rhythm strips felt confident was AF[ib].”

He added: “AF[ib] lasting more than 1 hour crosses the threshold for most practitioners I know to feel confident in treating the patient with anticoagulation. If it was symptomatic AF, this wouldn’t even be a question.”

Dr. Schwamm made the point that device-detected A AFib F has been accepted as worthy of treatment in patients after cryptogenic stroke.

“If we are honest with ourselves and if we have no hesitation in starting anticoagulation in a patient with cryptogenic stroke who has had device-detected AF 6 months later, should we decide that if the patient has had a lacunar stroke, we can ignore that same device-detected fibrillation?”

He put forward the idea that, at some level, all stroke is cryptogenic. “We never know for sure what the cause was. We have hypotheses, we have associations, but we don’t really know. So how much should we weigh that presumptive etiology in terms of how we interpret a rhythm disturbance of fibrillation?”

When looking for predictors of AFib in this study, the investigators found that patients were more likely to have an episode of AFib detected if they had one of the four following risk factors: congestive heart failure, left atrial enlargement, obesity, or QRS prolongation.

“In patients with any one of those four factors, 30% of those had device-detected AF[ib]. These are same predictors of AF[ib] that we are all accustomed to,” Dr. Schwamm said.
 

Shared decision-making

Dr. Schwamm said in an interview that, in his practice, for these patients, the decision as to whether to use continuous monitoring is made with the patient through shared decision-making.

“We discuss the chance that they could have AF[ib], and I suggest that it might be worth looking for it, but there are factors to be considered. There is a cost to the device, and reimbursement may depend on insurance coverage. Also, some patients may have strong feelings about having the chip implanted in their body.”

He says implanting the chip is easy. “It takes longer to check in at the front desk than to put the device in. It is injected under the skin. It just needs two stitches and a Band-Aid.” The device connects with a smartphone, and the results are interpreted by a cardiologist.

Dr. Schwamm pointed out that the optimal antithrombotic regimen for these patients in whom AFib is detected remains uncertain and should be the focus of future research.

“Do we just stick to antiplatelet therapy or advance to anticoagulation? In moving to an anticoagulant, are we providing less effective prevention for the atherosclerotic stroke risk at the expense of reducing the AF[ib]-related stroke risk? That may be a reasonable trade-off because we know the disability from AF[ib]-associated stroke is much higher.

“Or perhaps the optimal therapy is aspirin plus low-dose anticoagulant? Or left atrial appendage closure and an antiplatelet for patients at a higher risk of bleeding?” he said. “These are the really important questions we need to start asking.”

He added that he hopes a future study will address these questions, but he noted that it would have to be a large study, that it would have to first identify these patients and then randomly assign them to anticoagulation or to no treatment. “That is quite a major undertaking.”

In the highlights presentation, Dr. Jovin said he was uncertain of which of these patients in whom AFib is detected would benefit from anticoagulation. He said he would also like to see a randomized trial on this. But he added: “This would be challenging, as there is the issue of whether there would be equipoise to allow us to randomize to a placebo.”

Dr. Sansing agreed. “I think it would be a hard sell. I would have to think carefully about randomizing a patient to anticoagulation therapy or no therapy who has been found to have AF[ib].”

Dr. Schwamm noted that the current STROKE-AF study was not designed or powered to detect differences in stroke recurrence rates and that there was no difference in stroke recurrence rates between the two arms. There was also no randomization with regard to treatment; choice of medication was left to the discretion of the treating physician.

But he noted that only for 3 of the 34 patients with recurrent stroke in the continuous-monitor arm was AFib detected prior to the recurrent stroke, and only one of those three was receiving anticoagulation at the time of the recurrent stroke.

“These strokes were occurring in patients who did not have device-detected AF[ib],” Dr. Schwamm said. “This is because the population in this study were loaded with stroke risk factors and are at risk of recurrent stroke, but we don’t have the opportunity in this study to really understand the significance of the recurrent strokes.”

The STROKE AF trial was funded by Medtronic. Dr. Schwamm is a consultant to Medtronic.

A version of this article originally appeared on Medscape.com.

In the STROKE AF study, among patients who had a stroke presumably caused by atherosclerosis, the rate of atrial fibrillation (AFib) was almost 22% at 3 years, as detected by continuous monitoring.

The 3-year results from the study were presented by Lee H. Schwamm, MD, of Massachusetts General Hospital, Boston, at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

Dr. Schwamm said the high rate of AFib detection in this study suggests that continuous monitoring for AFib should be considered for a larger population of stroke patients, rather than just those with cryptogenic stroke.

“We found a much higher rate of AF[ib] than we expected in this population of patients who have had an atherosclerotic stroke,” Dr. Schwamm said in an interview.

“These AF[ib] occurrences were found by a device, so they are known as ‘device-documented AF[ib].’ The patient is not generally aware of symptoms, but 67% of the AF[ib] episodes lasted for more than 1 hour, showing that this is not trivial AF[ib]. This is meaningful AF[ib],” he said.

Dr. Schwamm said the major question is whether these cases of AFib that are detected with a device warrant treatment with anticoagulation. He noted that, in this study, clinicians decided to provide anticoagulation to 70%-80% of patients in whom AFib was detected.

“If we think it deserves treatment, then we have to look for it. And if we care about finding AF[ib], we have no choice but to monitor continuously,” he said.

“If this data doesn’t convince you that AF[ib] is present in this population, I don’t think any data will. Because it is consistent, it accumulates over time and looks remarkably similar to a set of data that we have all become very comfortable with – the CRYSTAL-AF study in patients with cryptogenic stroke,” he stated.

Dr. Schwamm noted that the STROKE AF trial was not based on the cause of the index stroke; rather, it was asking whether there are risk factors that could contribute to the 25% stroke recurrence rate in this population that are not covered in current guidelines.

“I’m really trying to move away from the anchor that I was trained in, which is to figure out the cause of the last stroke to help decide how to prevent the next stroke, towards more of a probabilistic model – of what is all the information I have at my disposal and how do I act on it to prevent the next stroke? We have to start thinking differently about building models for future stroke risk and determining therapy based on that,” he commented.
 

Changing practice

ISC 2023 program chair Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., and moderator of the session at which the results were presented, discussed the STROKE AF results in a highlights presentation.

“To me as clinician, these results are even more relevant than those at 12 months,” Dr. Jovin said. “The lesson I took is that AF[ib] is even more prevalent than we thought. The burden of AF[ib] is significant in these patients, and it doesn’t seem to be limited to a particular time. These are very thought-provoking results which are going to change clinical practice. I think the threshold for long-term monitoring will be lower.”

Comoderator Lauren Sansing, MD, Yale University, New Haven, Conn., added: “This study shows that the longer we monitor, the more patients with AF[ib] we are likely to pick up. And because in two-thirds of patients with AF[ib], it lasted longer than 1 hour, I do believe this was clinically relevant AF[ib]. The question now is, do we monitor everyone? I think it puts the burden on us to search for AF[ib] in our patients.”

In his presentation, Dr. Schwamm explained that, on the basis of the CRYSTAL-AF study, insertable cardiac monitoring devices are frequently used to identify poststroke AFib in patients with cryptogenic stroke. In the device-monitored arm of that study, AFib was detected in 12.4% of patients over 12 months versus 2.0% in the control arm.

“However, we don’t know how often AF[ib] is detected in other presumed stroke types – largely those due to atherosclerosis,” he said.

He pointed out that, at present, long-term monitoring post stroke for the detection of AFib is not currently recommended for patients with ischemic stroke, owing to presumed small-vessel occlusion or large-artery atherosclerosis.

“In these patients, we are not suspecting AF[ib] because we believe the cause of the stroke was not embolic. But we wanted to investigate what the AF[ib] risk is in these patients, who often have multiple stroke risk factors,” he said.

The trial enrolled 496 patients at 33 centers in the United States. Eligible patients were aged 60 years or older or aged 50-59 years with at least one additional stroke risk factor and had an index stroke that was attributed to large-artery or small-vessel disease. Patients were randomly assigned either to continuous monitoring with the Reveal LINQ device (Medtronic) or to the control arm following site-specific standard of care for AFib detection.

Dr. Schwamm noted that usual care for these patients normally involves monitoring for just a few days while in hospital, but this picks up less than 5% of AFib occurrences.

Baseline characteristics of patients in the STROKE AF study showed that the enrolled population was at high risk for stroke, with a CHADSVASC score of 5. But the index strokes were generally small; the median National Institutes of Health Stroke Scale score was 2.

Results at 12 months, reported 2 years ago, showed a 12.5% incidence of AFib with continuous monitoring versus 1.8% with standard of care (hazard ratio, 7.7; P < .001), rates similar to that found in the CRYSTAL-AF study.

By 3 years, the rate of detected AFib had risen to 21.7% in the continuous monitoring arm versus 2.4% in the control arm (HR, 10.0; P < .001).

“At 12 months, we were seven times more likely to detect AF[ib] with continuous monitoring in these patients, and by 3 years, it was 10 times more likely that AF would be detected with continuous monitoring. I think we’ve settled the question of the best way to find AF[ib] in these patients – it is with an inserted device,” Dr. Schwamm said.

“We have also shown that this is not a transient rise in AFib after the stroke which then diminishes over the next few years. It is a continuous and progressive detection of AF[ib].”

Dr. Schwamm pointed out that 88% of the recorded AFib episodes were asymptomatic. “So relying on patients self-reporting symptoms when deciding who to monitor is unreliable and not a sensible strategy.”

The median time to the first adjudicated AFib episode at 12-month follow-up was 99 days; at the 3-year follow-up, it was 284 days.

“This shows that 30 days of monitoring with an external patch is not sufficient to exclude the presence of AF[ib]. And this really argues for a strategy of immediate insertion of cardiac monitor placement if your goal is to look for AF[ib],” Dr. Schwamm commented.
 

Is this clinically relevant AFib?

Dr. Schwamm acknowledged that there is a question of whether device-detected AFib should be thought about in the same way as clinically detected AFib with respect to future stroke risk.

He noted that, in this study, 67.4% of patients for whom AFib was detected by continuous monitoring (31 of 46 patients) had at least one episode of AFib that lasted more than 1 hour.

“This is not a trivial little squiggle of something on an EKG which then goes away. This is of significant duration that the cardiologist who adjudicated these rhythm strips felt confident was AF[ib].”

He added: “AF[ib] lasting more than 1 hour crosses the threshold for most practitioners I know to feel confident in treating the patient with anticoagulation. If it was symptomatic AF, this wouldn’t even be a question.”

Dr. Schwamm made the point that device-detected A AFib F has been accepted as worthy of treatment in patients after cryptogenic stroke.

“If we are honest with ourselves and if we have no hesitation in starting anticoagulation in a patient with cryptogenic stroke who has had device-detected AF 6 months later, should we decide that if the patient has had a lacunar stroke, we can ignore that same device-detected fibrillation?”

He put forward the idea that, at some level, all stroke is cryptogenic. “We never know for sure what the cause was. We have hypotheses, we have associations, but we don’t really know. So how much should we weigh that presumptive etiology in terms of how we interpret a rhythm disturbance of fibrillation?”

When looking for predictors of AFib in this study, the investigators found that patients were more likely to have an episode of AFib detected if they had one of the four following risk factors: congestive heart failure, left atrial enlargement, obesity, or QRS prolongation.

“In patients with any one of those four factors, 30% of those had device-detected AF[ib]. These are same predictors of AF[ib] that we are all accustomed to,” Dr. Schwamm said.
 

Shared decision-making

Dr. Schwamm said in an interview that, in his practice, for these patients, the decision as to whether to use continuous monitoring is made with the patient through shared decision-making.

“We discuss the chance that they could have AF[ib], and I suggest that it might be worth looking for it, but there are factors to be considered. There is a cost to the device, and reimbursement may depend on insurance coverage. Also, some patients may have strong feelings about having the chip implanted in their body.”

He says implanting the chip is easy. “It takes longer to check in at the front desk than to put the device in. It is injected under the skin. It just needs two stitches and a Band-Aid.” The device connects with a smartphone, and the results are interpreted by a cardiologist.

Dr. Schwamm pointed out that the optimal antithrombotic regimen for these patients in whom AFib is detected remains uncertain and should be the focus of future research.

“Do we just stick to antiplatelet therapy or advance to anticoagulation? In moving to an anticoagulant, are we providing less effective prevention for the atherosclerotic stroke risk at the expense of reducing the AF[ib]-related stroke risk? That may be a reasonable trade-off because we know the disability from AF[ib]-associated stroke is much higher.

“Or perhaps the optimal therapy is aspirin plus low-dose anticoagulant? Or left atrial appendage closure and an antiplatelet for patients at a higher risk of bleeding?” he said. “These are the really important questions we need to start asking.”

He added that he hopes a future study will address these questions, but he noted that it would have to be a large study, that it would have to first identify these patients and then randomly assign them to anticoagulation or to no treatment. “That is quite a major undertaking.”

In the highlights presentation, Dr. Jovin said he was uncertain of which of these patients in whom AFib is detected would benefit from anticoagulation. He said he would also like to see a randomized trial on this. But he added: “This would be challenging, as there is the issue of whether there would be equipoise to allow us to randomize to a placebo.”

Dr. Sansing agreed. “I think it would be a hard sell. I would have to think carefully about randomizing a patient to anticoagulation therapy or no therapy who has been found to have AF[ib].”

Dr. Schwamm noted that the current STROKE-AF study was not designed or powered to detect differences in stroke recurrence rates and that there was no difference in stroke recurrence rates between the two arms. There was also no randomization with regard to treatment; choice of medication was left to the discretion of the treating physician.

But he noted that only for 3 of the 34 patients with recurrent stroke in the continuous-monitor arm was AFib detected prior to the recurrent stroke, and only one of those three was receiving anticoagulation at the time of the recurrent stroke.

“These strokes were occurring in patients who did not have device-detected AF[ib],” Dr. Schwamm said. “This is because the population in this study were loaded with stroke risk factors and are at risk of recurrent stroke, but we don’t have the opportunity in this study to really understand the significance of the recurrent strokes.”

The STROKE AF trial was funded by Medtronic. Dr. Schwamm is a consultant to Medtronic.

A version of this article originally appeared on Medscape.com.

In the STROKE AF study, among patients who had a stroke presumably caused by atherosclerosis, the rate of atrial fibrillation (AFib) was almost 22% at 3 years, as detected by continuous monitoring.

The 3-year results from the study were presented by Lee H. Schwamm, MD, of Massachusetts General Hospital, Boston, at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

Dr. Schwamm said the high rate of AFib detection in this study suggests that continuous monitoring for AFib should be considered for a larger population of stroke patients, rather than just those with cryptogenic stroke.

“We found a much higher rate of AF[ib] than we expected in this population of patients who have had an atherosclerotic stroke,” Dr. Schwamm said in an interview.

“These AF[ib] occurrences were found by a device, so they are known as ‘device-documented AF[ib].’ The patient is not generally aware of symptoms, but 67% of the AF[ib] episodes lasted for more than 1 hour, showing that this is not trivial AF[ib]. This is meaningful AF[ib],” he said.

Dr. Schwamm said the major question is whether these cases of AFib that are detected with a device warrant treatment with anticoagulation. He noted that, in this study, clinicians decided to provide anticoagulation to 70%-80% of patients in whom AFib was detected.

“If we think it deserves treatment, then we have to look for it. And if we care about finding AF[ib], we have no choice but to monitor continuously,” he said.

“If this data doesn’t convince you that AF[ib] is present in this population, I don’t think any data will. Because it is consistent, it accumulates over time and looks remarkably similar to a set of data that we have all become very comfortable with – the CRYSTAL-AF study in patients with cryptogenic stroke,” he stated.

Dr. Schwamm noted that the STROKE AF trial was not based on the cause of the index stroke; rather, it was asking whether there are risk factors that could contribute to the 25% stroke recurrence rate in this population that are not covered in current guidelines.

“I’m really trying to move away from the anchor that I was trained in, which is to figure out the cause of the last stroke to help decide how to prevent the next stroke, towards more of a probabilistic model – of what is all the information I have at my disposal and how do I act on it to prevent the next stroke? We have to start thinking differently about building models for future stroke risk and determining therapy based on that,” he commented.
 

Changing practice

ISC 2023 program chair Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., and moderator of the session at which the results were presented, discussed the STROKE AF results in a highlights presentation.

“To me as clinician, these results are even more relevant than those at 12 months,” Dr. Jovin said. “The lesson I took is that AF[ib] is even more prevalent than we thought. The burden of AF[ib] is significant in these patients, and it doesn’t seem to be limited to a particular time. These are very thought-provoking results which are going to change clinical practice. I think the threshold for long-term monitoring will be lower.”

Comoderator Lauren Sansing, MD, Yale University, New Haven, Conn., added: “This study shows that the longer we monitor, the more patients with AF[ib] we are likely to pick up. And because in two-thirds of patients with AF[ib], it lasted longer than 1 hour, I do believe this was clinically relevant AF[ib]. The question now is, do we monitor everyone? I think it puts the burden on us to search for AF[ib] in our patients.”

In his presentation, Dr. Schwamm explained that, on the basis of the CRYSTAL-AF study, insertable cardiac monitoring devices are frequently used to identify poststroke AFib in patients with cryptogenic stroke. In the device-monitored arm of that study, AFib was detected in 12.4% of patients over 12 months versus 2.0% in the control arm.

“However, we don’t know how often AF[ib] is detected in other presumed stroke types – largely those due to atherosclerosis,” he said.

He pointed out that, at present, long-term monitoring post stroke for the detection of AFib is not currently recommended for patients with ischemic stroke, owing to presumed small-vessel occlusion or large-artery atherosclerosis.

“In these patients, we are not suspecting AF[ib] because we believe the cause of the stroke was not embolic. But we wanted to investigate what the AF[ib] risk is in these patients, who often have multiple stroke risk factors,” he said.

The trial enrolled 496 patients at 33 centers in the United States. Eligible patients were aged 60 years or older or aged 50-59 years with at least one additional stroke risk factor and had an index stroke that was attributed to large-artery or small-vessel disease. Patients were randomly assigned either to continuous monitoring with the Reveal LINQ device (Medtronic) or to the control arm following site-specific standard of care for AFib detection.

Dr. Schwamm noted that usual care for these patients normally involves monitoring for just a few days while in hospital, but this picks up less than 5% of AFib occurrences.

Baseline characteristics of patients in the STROKE AF study showed that the enrolled population was at high risk for stroke, with a CHADSVASC score of 5. But the index strokes were generally small; the median National Institutes of Health Stroke Scale score was 2.

Results at 12 months, reported 2 years ago, showed a 12.5% incidence of AFib with continuous monitoring versus 1.8% with standard of care (hazard ratio, 7.7; P < .001), rates similar to that found in the CRYSTAL-AF study.

By 3 years, the rate of detected AFib had risen to 21.7% in the continuous monitoring arm versus 2.4% in the control arm (HR, 10.0; P < .001).

“At 12 months, we were seven times more likely to detect AF[ib] with continuous monitoring in these patients, and by 3 years, it was 10 times more likely that AF would be detected with continuous monitoring. I think we’ve settled the question of the best way to find AF[ib] in these patients – it is with an inserted device,” Dr. Schwamm said.

“We have also shown that this is not a transient rise in AFib after the stroke which then diminishes over the next few years. It is a continuous and progressive detection of AF[ib].”

Dr. Schwamm pointed out that 88% of the recorded AFib episodes were asymptomatic. “So relying on patients self-reporting symptoms when deciding who to monitor is unreliable and not a sensible strategy.”

The median time to the first adjudicated AFib episode at 12-month follow-up was 99 days; at the 3-year follow-up, it was 284 days.

“This shows that 30 days of monitoring with an external patch is not sufficient to exclude the presence of AF[ib]. And this really argues for a strategy of immediate insertion of cardiac monitor placement if your goal is to look for AF[ib],” Dr. Schwamm commented.
 

Is this clinically relevant AFib?

Dr. Schwamm acknowledged that there is a question of whether device-detected AFib should be thought about in the same way as clinically detected AFib with respect to future stroke risk.

He noted that, in this study, 67.4% of patients for whom AFib was detected by continuous monitoring (31 of 46 patients) had at least one episode of AFib that lasted more than 1 hour.

“This is not a trivial little squiggle of something on an EKG which then goes away. This is of significant duration that the cardiologist who adjudicated these rhythm strips felt confident was AF[ib].”

He added: “AF[ib] lasting more than 1 hour crosses the threshold for most practitioners I know to feel confident in treating the patient with anticoagulation. If it was symptomatic AF, this wouldn’t even be a question.”

Dr. Schwamm made the point that device-detected A AFib F has been accepted as worthy of treatment in patients after cryptogenic stroke.

“If we are honest with ourselves and if we have no hesitation in starting anticoagulation in a patient with cryptogenic stroke who has had device-detected AF 6 months later, should we decide that if the patient has had a lacunar stroke, we can ignore that same device-detected fibrillation?”

He put forward the idea that, at some level, all stroke is cryptogenic. “We never know for sure what the cause was. We have hypotheses, we have associations, but we don’t really know. So how much should we weigh that presumptive etiology in terms of how we interpret a rhythm disturbance of fibrillation?”

When looking for predictors of AFib in this study, the investigators found that patients were more likely to have an episode of AFib detected if they had one of the four following risk factors: congestive heart failure, left atrial enlargement, obesity, or QRS prolongation.

“In patients with any one of those four factors, 30% of those had device-detected AF[ib]. These are same predictors of AF[ib] that we are all accustomed to,” Dr. Schwamm said.
 

Shared decision-making

Dr. Schwamm said in an interview that, in his practice, for these patients, the decision as to whether to use continuous monitoring is made with the patient through shared decision-making.

“We discuss the chance that they could have AF[ib], and I suggest that it might be worth looking for it, but there are factors to be considered. There is a cost to the device, and reimbursement may depend on insurance coverage. Also, some patients may have strong feelings about having the chip implanted in their body.”

He says implanting the chip is easy. “It takes longer to check in at the front desk than to put the device in. It is injected under the skin. It just needs two stitches and a Band-Aid.” The device connects with a smartphone, and the results are interpreted by a cardiologist.

Dr. Schwamm pointed out that the optimal antithrombotic regimen for these patients in whom AFib is detected remains uncertain and should be the focus of future research.

“Do we just stick to antiplatelet therapy or advance to anticoagulation? In moving to an anticoagulant, are we providing less effective prevention for the atherosclerotic stroke risk at the expense of reducing the AF[ib]-related stroke risk? That may be a reasonable trade-off because we know the disability from AF[ib]-associated stroke is much higher.

“Or perhaps the optimal therapy is aspirin plus low-dose anticoagulant? Or left atrial appendage closure and an antiplatelet for patients at a higher risk of bleeding?” he said. “These are the really important questions we need to start asking.”

He added that he hopes a future study will address these questions, but he noted that it would have to be a large study, that it would have to first identify these patients and then randomly assign them to anticoagulation or to no treatment. “That is quite a major undertaking.”

In the highlights presentation, Dr. Jovin said he was uncertain of which of these patients in whom AFib is detected would benefit from anticoagulation. He said he would also like to see a randomized trial on this. But he added: “This would be challenging, as there is the issue of whether there would be equipoise to allow us to randomize to a placebo.”

Dr. Sansing agreed. “I think it would be a hard sell. I would have to think carefully about randomizing a patient to anticoagulation therapy or no therapy who has been found to have AF[ib].”

Dr. Schwamm noted that the current STROKE-AF study was not designed or powered to detect differences in stroke recurrence rates and that there was no difference in stroke recurrence rates between the two arms. There was also no randomization with regard to treatment; choice of medication was left to the discretion of the treating physician.

But he noted that only for 3 of the 34 patients with recurrent stroke in the continuous-monitor arm was AFib detected prior to the recurrent stroke, and only one of those three was receiving anticoagulation at the time of the recurrent stroke.

“These strokes were occurring in patients who did not have device-detected AF[ib],” Dr. Schwamm said. “This is because the population in this study were loaded with stroke risk factors and are at risk of recurrent stroke, but we don’t have the opportunity in this study to really understand the significance of the recurrent strokes.”

The STROKE AF trial was funded by Medtronic. Dr. Schwamm is a consultant to Medtronic.

A version of this article originally appeared on Medscape.com.

A novel anti-inflammatory agent given to stroke patients receiving endovascular therapy significantly cut the mortality rate, reduced infarct size, and improved disability, preliminary results of a first-in-human study show.

The findings illustrate that it is possible to improve outcomes for stroke patients “not only with reperfusion therapy but with neuroprotectants,” study author Macarena Hernandez, PhD, associate professor, University Complutense, Madrid, told this news organization.

Dr. Hernandez said she hopes these positive results will spur investigation into other neuroprotective agents.

The findings were presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
 

Best doses

The study investigated ApTOLL, which blocks the TOLL-like receptor 4 (TLR4) that induces inflammation after a stroke. Previous studies found that ApTOLL protected brain tissue in animal models of stroke.

The phase 1B part of the study found no safety issues and determined the best two doses to be used in phase 2A were 0.05 mg/kg and 0.2 mg/kg.

The analysis included 139 patients at 14 centers in Spain and France (mean age, about 70 years; 42% women) who had a large-vessel occlusion and were eligible for endovascular therapy.

“Our aim was to have a very homogeneous population” to try to replicate in humans what had worked in animals, another study author, Marc Ribó, MD, interventional neurologist, Hospital Vall d’Hebron, Barcelona, told this news organization.

Study participants had an Alberta Stroke Program Early CT Score (ASPECTS) of 5-10, and estimated infarct core volume on CT-perfusion was 5-70 mL. All were treated within 6 hours of stroke onset.

Researchers randomly assigned patients to receive the low dose of the drug, the high dose of the drug, or placebo. The drug was administered intravenously over a 30-minute period just prior to the groin puncture for the thrombectomy procedure.

“So, the drug had already started to work when they underwent the usual standard practice, the thrombectomy,” said Dr. Ribó.

Those who were eligible also received tissue plasminogen activator.

The primary endpoint was safety, including death, symptomatic intracranial hemorrhage (SICH), and recurrent stroke.
 

Lower mortality

At 90 days, there was a statistically significant lower mortality rate in the high-dose group, compared with the group that received placebo (4.76% vs. 18.18%).

The mortality rate was 26.19% in the low-dose group, but Dr. Ribó stressed that this dose was a quarter of the higher dose and so performed “much more like placebo.”

The higher dose also yielded a better SICH outcome (4.76% of patients vs. 7.27% for placebo and 7.14% for the lower dose). And it was superior in terms of brain edema (2.4% of the population vs. 7.3% for the placebo and 4.8% for the low-dose groups).

About 7.1% of the high-dose group, 3.7% of the placebo group, and 4.8% of the low-dose group had a recurrent transient ischemic attack or stroke.

A secondary efficacy endpoint was infarct volume on MRI at 72 hours. Here, for the higher-dose group, mean infarct volume was reduced, compared with the patients who received placebo (–29.31 cc; 90% confidence interval, –49.28 to –9.34).

This higher dose was also superior for the secondary outcome of National Institutes of Health Stroke Scale score at 72 hours and for the disability outcome on the modified Rankin Score (mRS).
 

Clear shift in disability

“There was a clear shift toward less disability across levels of the mRS score in the high-dose group at 90 days,” said Dr. Ribó.

He added that he and his colleagues are “very happy” with these results, as they reflect “a consistency” of outcomes.

“We observed that the infarct volumes were lower in the high-dose group, and that led to a significant lower NIH score, meaning less clinical neurological symptoms at 72 hours, and finally, this led to less disability at 90 days.”

These results are “very exciting,” Dr. Hernandez added. “This is the first neuroprotectant that has demonstrated this acute effect in reducing deaths, in reducing the infarct volume and improving functionality long-term in patients treated with the higher dose.”

Dr. Ribó noted the treatment would eventually be used in addition to reperfusion therapy. “It’s not competing with reperfusion treatment; it’s an additional layer” of treatment.

Although it would initially be offered only to patients eligible for thrombectomy, researchers will explore the drug’s effectiveness for other stroke patients, said Dr. Ribó. “We wanted to secure this indication, and from there, progressively expand to other profiles of stroke patients, and even to patients with intracranial hemorrhage.”

The study confirmed the safety of the drug. “There were no safety issues at all,” said Dr. Ribó. “We were initially concerned that an anti-inflammatory in these patients could lead to higher rates of infections, but this was absolutely not the case.”

The next step is to confirm the effects in a larger, multicenter study, which is planned to launch at the end of this year, said Dr. Hernandez.
 

‘Very robust results’

In a comment, Philip B. Gorelick, MD, professor of neurology, Northwestern University, Chicago, said that, while this was a small early-phase study, the results are “very robust.”

“The authors demonstrated proof of a neuroprotective effect; they showed at 90 days that the death rates were substantially reduced by about four times – 4% vs. 18% – and the size of the damaged tissue at about 72 hours was reduced by 40%,” said Dr. Gorelick, who did not participate in the study.

He also noted that the disability was “less pronounced” at 90 days in the 0.2 mg/kg group.

“So overall, these are very encouraging results,” said Dr. Gorelick. “We have had a lot of difficulty finding neuroprotectant drugs that work, and this drug, in combination with endovascular therapy, seems to be very promising.”

However, he stressed the drug “is not ready for prime-time practice.”

“The proof in the pudding will be in the large-scale main phase 3 trials,” he added.

The study was funded by aptaTargets. Dr. Hernandez is chief scientific officer at aptaTargets. Dr. Ribó is an adviser at AptaTargets; a consultant at Medtronic; has ownership interest in Anaconda and NoraHealth; is a consultant for Cerenovus and Philips; and has stock options at Methink. Dr. Gorelick has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A novel anti-inflammatory agent given to stroke patients receiving endovascular therapy significantly cut the mortality rate, reduced infarct size, and improved disability, preliminary results of a first-in-human study show.

The findings illustrate that it is possible to improve outcomes for stroke patients “not only with reperfusion therapy but with neuroprotectants,” study author Macarena Hernandez, PhD, associate professor, University Complutense, Madrid, told this news organization.

Dr. Hernandez said she hopes these positive results will spur investigation into other neuroprotective agents.

The findings were presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
 

Best doses

The study investigated ApTOLL, which blocks the TOLL-like receptor 4 (TLR4) that induces inflammation after a stroke. Previous studies found that ApTOLL protected brain tissue in animal models of stroke.

The phase 1B part of the study found no safety issues and determined the best two doses to be used in phase 2A were 0.05 mg/kg and 0.2 mg/kg.

The analysis included 139 patients at 14 centers in Spain and France (mean age, about 70 years; 42% women) who had a large-vessel occlusion and were eligible for endovascular therapy.

“Our aim was to have a very homogeneous population” to try to replicate in humans what had worked in animals, another study author, Marc Ribó, MD, interventional neurologist, Hospital Vall d’Hebron, Barcelona, told this news organization.

Study participants had an Alberta Stroke Program Early CT Score (ASPECTS) of 5-10, and estimated infarct core volume on CT-perfusion was 5-70 mL. All were treated within 6 hours of stroke onset.

Researchers randomly assigned patients to receive the low dose of the drug, the high dose of the drug, or placebo. The drug was administered intravenously over a 30-minute period just prior to the groin puncture for the thrombectomy procedure.

“So, the drug had already started to work when they underwent the usual standard practice, the thrombectomy,” said Dr. Ribó.

Those who were eligible also received tissue plasminogen activator.

The primary endpoint was safety, including death, symptomatic intracranial hemorrhage (SICH), and recurrent stroke.
 

Lower mortality

At 90 days, there was a statistically significant lower mortality rate in the high-dose group, compared with the group that received placebo (4.76% vs. 18.18%).

The mortality rate was 26.19% in the low-dose group, but Dr. Ribó stressed that this dose was a quarter of the higher dose and so performed “much more like placebo.”

The higher dose also yielded a better SICH outcome (4.76% of patients vs. 7.27% for placebo and 7.14% for the lower dose). And it was superior in terms of brain edema (2.4% of the population vs. 7.3% for the placebo and 4.8% for the low-dose groups).

About 7.1% of the high-dose group, 3.7% of the placebo group, and 4.8% of the low-dose group had a recurrent transient ischemic attack or stroke.

A secondary efficacy endpoint was infarct volume on MRI at 72 hours. Here, for the higher-dose group, mean infarct volume was reduced, compared with the patients who received placebo (–29.31 cc; 90% confidence interval, –49.28 to –9.34).

This higher dose was also superior for the secondary outcome of National Institutes of Health Stroke Scale score at 72 hours and for the disability outcome on the modified Rankin Score (mRS).
 

Clear shift in disability

“There was a clear shift toward less disability across levels of the mRS score in the high-dose group at 90 days,” said Dr. Ribó.

He added that he and his colleagues are “very happy” with these results, as they reflect “a consistency” of outcomes.

“We observed that the infarct volumes were lower in the high-dose group, and that led to a significant lower NIH score, meaning less clinical neurological symptoms at 72 hours, and finally, this led to less disability at 90 days.”

These results are “very exciting,” Dr. Hernandez added. “This is the first neuroprotectant that has demonstrated this acute effect in reducing deaths, in reducing the infarct volume and improving functionality long-term in patients treated with the higher dose.”

Dr. Ribó noted the treatment would eventually be used in addition to reperfusion therapy. “It’s not competing with reperfusion treatment; it’s an additional layer” of treatment.

Although it would initially be offered only to patients eligible for thrombectomy, researchers will explore the drug’s effectiveness for other stroke patients, said Dr. Ribó. “We wanted to secure this indication, and from there, progressively expand to other profiles of stroke patients, and even to patients with intracranial hemorrhage.”

The study confirmed the safety of the drug. “There were no safety issues at all,” said Dr. Ribó. “We were initially concerned that an anti-inflammatory in these patients could lead to higher rates of infections, but this was absolutely not the case.”

The next step is to confirm the effects in a larger, multicenter study, which is planned to launch at the end of this year, said Dr. Hernandez.
 

‘Very robust results’

In a comment, Philip B. Gorelick, MD, professor of neurology, Northwestern University, Chicago, said that, while this was a small early-phase study, the results are “very robust.”

“The authors demonstrated proof of a neuroprotective effect; they showed at 90 days that the death rates were substantially reduced by about four times – 4% vs. 18% – and the size of the damaged tissue at about 72 hours was reduced by 40%,” said Dr. Gorelick, who did not participate in the study.

He also noted that the disability was “less pronounced” at 90 days in the 0.2 mg/kg group.

“So overall, these are very encouraging results,” said Dr. Gorelick. “We have had a lot of difficulty finding neuroprotectant drugs that work, and this drug, in combination with endovascular therapy, seems to be very promising.”

However, he stressed the drug “is not ready for prime-time practice.”

“The proof in the pudding will be in the large-scale main phase 3 trials,” he added.

The study was funded by aptaTargets. Dr. Hernandez is chief scientific officer at aptaTargets. Dr. Ribó is an adviser at AptaTargets; a consultant at Medtronic; has ownership interest in Anaconda and NoraHealth; is a consultant for Cerenovus and Philips; and has stock options at Methink. Dr. Gorelick has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A novel anti-inflammatory agent given to stroke patients receiving endovascular therapy significantly cut the mortality rate, reduced infarct size, and improved disability, preliminary results of a first-in-human study show.

The findings illustrate that it is possible to improve outcomes for stroke patients “not only with reperfusion therapy but with neuroprotectants,” study author Macarena Hernandez, PhD, associate professor, University Complutense, Madrid, told this news organization.

Dr. Hernandez said she hopes these positive results will spur investigation into other neuroprotective agents.

The findings were presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
 

Best doses

The study investigated ApTOLL, which blocks the TOLL-like receptor 4 (TLR4) that induces inflammation after a stroke. Previous studies found that ApTOLL protected brain tissue in animal models of stroke.

The phase 1B part of the study found no safety issues and determined the best two doses to be used in phase 2A were 0.05 mg/kg and 0.2 mg/kg.

The analysis included 139 patients at 14 centers in Spain and France (mean age, about 70 years; 42% women) who had a large-vessel occlusion and were eligible for endovascular therapy.

“Our aim was to have a very homogeneous population” to try to replicate in humans what had worked in animals, another study author, Marc Ribó, MD, interventional neurologist, Hospital Vall d’Hebron, Barcelona, told this news organization.

Study participants had an Alberta Stroke Program Early CT Score (ASPECTS) of 5-10, and estimated infarct core volume on CT-perfusion was 5-70 mL. All were treated within 6 hours of stroke onset.

Researchers randomly assigned patients to receive the low dose of the drug, the high dose of the drug, or placebo. The drug was administered intravenously over a 30-minute period just prior to the groin puncture for the thrombectomy procedure.

“So, the drug had already started to work when they underwent the usual standard practice, the thrombectomy,” said Dr. Ribó.

Those who were eligible also received tissue plasminogen activator.

The primary endpoint was safety, including death, symptomatic intracranial hemorrhage (SICH), and recurrent stroke.
 

Lower mortality

At 90 days, there was a statistically significant lower mortality rate in the high-dose group, compared with the group that received placebo (4.76% vs. 18.18%).

The mortality rate was 26.19% in the low-dose group, but Dr. Ribó stressed that this dose was a quarter of the higher dose and so performed “much more like placebo.”

The higher dose also yielded a better SICH outcome (4.76% of patients vs. 7.27% for placebo and 7.14% for the lower dose). And it was superior in terms of brain edema (2.4% of the population vs. 7.3% for the placebo and 4.8% for the low-dose groups).

About 7.1% of the high-dose group, 3.7% of the placebo group, and 4.8% of the low-dose group had a recurrent transient ischemic attack or stroke.

A secondary efficacy endpoint was infarct volume on MRI at 72 hours. Here, for the higher-dose group, mean infarct volume was reduced, compared with the patients who received placebo (–29.31 cc; 90% confidence interval, –49.28 to –9.34).

This higher dose was also superior for the secondary outcome of National Institutes of Health Stroke Scale score at 72 hours and for the disability outcome on the modified Rankin Score (mRS).
 

Clear shift in disability

“There was a clear shift toward less disability across levels of the mRS score in the high-dose group at 90 days,” said Dr. Ribó.

He added that he and his colleagues are “very happy” with these results, as they reflect “a consistency” of outcomes.

“We observed that the infarct volumes were lower in the high-dose group, and that led to a significant lower NIH score, meaning less clinical neurological symptoms at 72 hours, and finally, this led to less disability at 90 days.”

These results are “very exciting,” Dr. Hernandez added. “This is the first neuroprotectant that has demonstrated this acute effect in reducing deaths, in reducing the infarct volume and improving functionality long-term in patients treated with the higher dose.”

Dr. Ribó noted the treatment would eventually be used in addition to reperfusion therapy. “It’s not competing with reperfusion treatment; it’s an additional layer” of treatment.

Although it would initially be offered only to patients eligible for thrombectomy, researchers will explore the drug’s effectiveness for other stroke patients, said Dr. Ribó. “We wanted to secure this indication, and from there, progressively expand to other profiles of stroke patients, and even to patients with intracranial hemorrhage.”

The study confirmed the safety of the drug. “There were no safety issues at all,” said Dr. Ribó. “We were initially concerned that an anti-inflammatory in these patients could lead to higher rates of infections, but this was absolutely not the case.”

The next step is to confirm the effects in a larger, multicenter study, which is planned to launch at the end of this year, said Dr. Hernandez.
 

‘Very robust results’

In a comment, Philip B. Gorelick, MD, professor of neurology, Northwestern University, Chicago, said that, while this was a small early-phase study, the results are “very robust.”

“The authors demonstrated proof of a neuroprotective effect; they showed at 90 days that the death rates were substantially reduced by about four times – 4% vs. 18% – and the size of the damaged tissue at about 72 hours was reduced by 40%,” said Dr. Gorelick, who did not participate in the study.

He also noted that the disability was “less pronounced” at 90 days in the 0.2 mg/kg group.

“So overall, these are very encouraging results,” said Dr. Gorelick. “We have had a lot of difficulty finding neuroprotectant drugs that work, and this drug, in combination with endovascular therapy, seems to be very promising.”

However, he stressed the drug “is not ready for prime-time practice.”

“The proof in the pudding will be in the large-scale main phase 3 trials,” he added.

The study was funded by aptaTargets. Dr. Hernandez is chief scientific officer at aptaTargets. Dr. Ribó is an adviser at AptaTargets; a consultant at Medtronic; has ownership interest in Anaconda and NoraHealth; is a consultant for Cerenovus and Philips; and has stock options at Methink. Dr. Gorelick has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.