Stroke

A large randomized trial that was investigating intensive lowering of blood pressure in acute ischemic stroke patients who had undergone mechanical thrombectomy has been stopped early because of safety concerns.

“Intensive control of systolic blood pressure to lower than 120 mm Hg should be avoided to prevent compromising the functional recovery of patients who have received endovascular thrombectomy for acute ischemic stroke due to intracranial large-vessel occlusion,” the investigators conclude.

Results from the ENCHANTED2/MT trial were presented by Craig Anderson, MD, professor of neurology and epidemiology, University of New South Wales, Sydney, during the 14th World Stroke Congress (WSC) in Singapore.

The study was simultaneously published online in The Lancet.

“What our results have pretty convincingly shown is that in acute stroke patients who have undergone mechanical thrombectomy, lowering blood pressure down to a systolic of 120 mm Hg for 3 days is too low for too long. We shouldn’t go that far down,” Dr. Anderson said in an interview.

Dr. Anderson said the trial has provided an important message for clinical practice.

“This result is not what we expected, but it is a definitive result and gives us a lower safety margin for blood pressure in acute ischemic stroke patients. This, in itself, is a big step forward.”

He noted that the optimum blood pressure for these patients is not known.

“We need to do further trials to determine optimum blood pressure in these acute patients, but perhaps we should be aiming more towards 140 mm Hg,” he suggested.

“But this trial shows us that in patients who have had successful clot retrieval with endovascular treatment for acute ischemic stroke, careful blood pressure management is important to avoid levels becoming too low. We have to make sure we don’t overshoot down to 120 mm Hg or below.”

The chair of the WSC session at which the trial was presented, Jeyaraj Pandian, MD, head of neurology at Christian Medical College, Ludhiana, India, who is the current vice-president of the World Stroke Organization, said: “This is a very important result. It has major practical implications.”

As background, Dr. Anderson explained that elevated blood pressure is very common in patients who have an acute ischemic stroke, and the higher the blood pressure, the higher the chances of having a worse outcome.

“Theoretically, if we can control the blood pressure, we may be able to improve outcomes,” he said.

In 2019, the first ENCHANTED trial reported that controlling blood pressure by a moderate amount – to around 140 mm Hg, which is lower than currently recommended in the guidelines – was linked to a reduction in bleeding complications of thrombolysis and appeared safe, but it did not improve recovery, Dr. Anderson noted.

“This trial was done before mechanical thrombectomy became routinely adopted, and this procedure has now become the standard of care for large-vessel occlusion strokes, but we don’t know what we should do about blood pressure in these patients,” he added.

A smaller French trial has suggested lowering blood pressure to 130 mm Hg, rather than a more liberal 130-180 mm Hg, was safe after successful mechanical thrombectomy, but there was no effect on functional outcome.

“In stroke patients with a large-vessel occlusion, blood pressure is often elevated to very high levels. There are wide ranges of opinions on what to do about this – whether it should be lowered, and by how much,” Dr. Anderson said. “We conducted the current ENCHANTED2/MT trial to look at this issue.”

The trial randomly assigned patients who had undergone successful mechanical clot retrieval and reperfusion but whose blood pressure was still elevated to two groups. In one group, blood pressure was aggressively lowered to less than 120 mm Hg within 1 hour of reperfusion, and blood pressure was kept at this level for 3 days. In the other group, a more liberal approach was used: Blood pressure was kept at 140-180 mm Hg.

The primary endpoint was disability, as measured by the Modified Rankin Scale (mRS) score at 90 days.

The study was started in China with the intention of expanding recruitment internationally. The planned enrollment was more than 2,000 patients.

However, in March of 2022, after 821 patients had been enrolled, the data safety monitoring board (DSMB) recommended that recruitment into the trial be suspended because of a safety signal. All of the patients who had been recruited were from China.

These patients were followed to obtain the 3-month outcome results, after which the DSMB recommended that the trial be stopped because safety was still a problem.

Mean systolic blood pressure was 125 mm Hg at 1 hour and 121 mm Hg at 24 hours in the more intensive-treatment group; it was 143 mm Hg at 1 hour and 139 mm Hg at 24 hours in the less intensive-treatment group, giving an adjusted mean difference over 24 hours of 18 mm Hg.
 

Worse disability scores

Results showed that the patients who underwent the more intensive blood pressure lowering had more disability at 3-month follow-up, with worse scores on a shift analysis of the mRS than those in the less intensive group (common odds ratio, 1.37; 95% confidence interval, 1.07-1.76).

The unfavorable shift in mRS scores in the more intensive group was consistent in adjusted sensitivity analysis, and there was no significant heterogeneity in the treatment effect on the primary outcome across all prespecified subgroups.

The incidence of death or neurologic deterioration at 7 days was higher in the more intensive-treatment group than the less intensive-treatment group (common OR, 1.53), and a between-group difference emerged at 24 hours.

The incidence of death or disability (mRS scores, 3-6) at 90 days was higher among patients in the more intensive-treatment group than the less intensive-treatment group (53% vs. 39%; OR, 1.85; P = .0001).

Among those who survived, more patients in the more intensive-treatment group had major disability (mRS scores, 3-5) at 90 days than did patients in the less intensive-treatment group (43% vs. 28%; OR, 2.07; P = .0001).
 

No difference in ICH or severe hypotension episodes

The incidence of symptomatic intracranial hemorrhage, mortality, and serious adverse events did not significantly differ between the two groups. There were no significant differences in recurrent ischemic stroke events at 90 days, and no episodes of severe hypotension were reported as a serious adverse event.

“Our results show that intensive lowering of blood pressure appears to be associated with worsening physical disability. While there was no difference in mortality rates between the two groups, the lower blood pressure appeared to compromise the ability to recover from the stroke,” Dr. Anderson said.

On the possible mechanism of harm, he suggested that the intensive blood pressure reduction might be interfering with blood flow through the injured part of the brain and impeding the ability to recover from the clot removal procedure.
 

What levels should be aimed for?

Dr. Anderson stressed that it was important to have conducted this trial.

“Current guidelines recommend very conservative level of blood pressure in acute ischemic stroke patients – to below 180 mm Hg. But no lower limit is recommended.

“Most clinicians aim for about the 140 mm Hg mark, but there is a large variation in opinion on what to do,” he said. “Some doctors treat aggressively, believing that lower pressures could be beneficial in preventing bleeding and swelling, and others prefer to keep levels higher. Our results have helped to give some guidance on this.”

Asked what he thought an optimum target would be, Dr. Anderson replied: “For now, I think a target of around 140 mm Hg systolic would be reasonable, and there is no evidence to move below that.”

Yvo Roos, MD, professor of acute neurology at University Medical Center, Amsterdam, a co-author of the ENCHANTED2/MT trial, also commented: “The real importance of these study results is that they show that lowering blood pressure too much is detrimental on outcome. My personal interpretation, looking at the results of this study but also on the previous studies, is that we should aim for a target of 140-150 mm Hg. This is true for patients with recanalization therapy. For patients without any therapy, I would even be more careful in lowering blood pressure and recommend just staying below 180 mm Hg.”

As to whether these results are generalizable to other populations, given that the patients were Chinese, Dr. Anderson noted that Asian people have higher rates of intracranial atherosclerosis and more blood pressure complications in the heart and kidney than White patients. Stroke management patterns also differ.

“These points raise questions about generalizability, and while I think this is an issue for consideration, I do not think it should detract from the clarity of these results,” he commented.

The study is supported by grants from the Shanghai Hospital Development Center, the National Health and Medical Research Council of Australia, the China Stroke Prevention Project, Shanghai Changhai Hospital, the Science and Technology Commission of Shanghai Municipality, Takeda China, Genesis Medtech, and Penumbra. Dr. Anderson has received grants from the National Health and Medical Research Council and Medical Research Futures Fund of Australia, the UK Medical Research Council, Penumbra, and Takeda China.

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

A large randomized trial that was investigating intensive lowering of blood pressure in acute ischemic stroke patients who had undergone mechanical thrombectomy has been stopped early because of safety concerns.

“Intensive control of systolic blood pressure to lower than 120 mm Hg should be avoided to prevent compromising the functional recovery of patients who have received endovascular thrombectomy for acute ischemic stroke due to intracranial large-vessel occlusion,” the investigators conclude.

Results from the ENCHANTED2/MT trial were presented by Craig Anderson, MD, professor of neurology and epidemiology, University of New South Wales, Sydney, during the 14th World Stroke Congress (WSC) in Singapore.

The study was simultaneously published online in The Lancet.

“What our results have pretty convincingly shown is that in acute stroke patients who have undergone mechanical thrombectomy, lowering blood pressure down to a systolic of 120 mm Hg for 3 days is too low for too long. We shouldn’t go that far down,” Dr. Anderson said in an interview.

Dr. Anderson said the trial has provided an important message for clinical practice.

“This result is not what we expected, but it is a definitive result and gives us a lower safety margin for blood pressure in acute ischemic stroke patients. This, in itself, is a big step forward.”

He noted that the optimum blood pressure for these patients is not known.

“We need to do further trials to determine optimum blood pressure in these acute patients, but perhaps we should be aiming more towards 140 mm Hg,” he suggested.

“But this trial shows us that in patients who have had successful clot retrieval with endovascular treatment for acute ischemic stroke, careful blood pressure management is important to avoid levels becoming too low. We have to make sure we don’t overshoot down to 120 mm Hg or below.”

The chair of the WSC session at which the trial was presented, Jeyaraj Pandian, MD, head of neurology at Christian Medical College, Ludhiana, India, who is the current vice-president of the World Stroke Organization, said: “This is a very important result. It has major practical implications.”

As background, Dr. Anderson explained that elevated blood pressure is very common in patients who have an acute ischemic stroke, and the higher the blood pressure, the higher the chances of having a worse outcome.

“Theoretically, if we can control the blood pressure, we may be able to improve outcomes,” he said.

In 2019, the first ENCHANTED trial reported that controlling blood pressure by a moderate amount – to around 140 mm Hg, which is lower than currently recommended in the guidelines – was linked to a reduction in bleeding complications of thrombolysis and appeared safe, but it did not improve recovery, Dr. Anderson noted.

“This trial was done before mechanical thrombectomy became routinely adopted, and this procedure has now become the standard of care for large-vessel occlusion strokes, but we don’t know what we should do about blood pressure in these patients,” he added.

A smaller French trial has suggested lowering blood pressure to 130 mm Hg, rather than a more liberal 130-180 mm Hg, was safe after successful mechanical thrombectomy, but there was no effect on functional outcome.

“In stroke patients with a large-vessel occlusion, blood pressure is often elevated to very high levels. There are wide ranges of opinions on what to do about this – whether it should be lowered, and by how much,” Dr. Anderson said. “We conducted the current ENCHANTED2/MT trial to look at this issue.”

The trial randomly assigned patients who had undergone successful mechanical clot retrieval and reperfusion but whose blood pressure was still elevated to two groups. In one group, blood pressure was aggressively lowered to less than 120 mm Hg within 1 hour of reperfusion, and blood pressure was kept at this level for 3 days. In the other group, a more liberal approach was used: Blood pressure was kept at 140-180 mm Hg.

The primary endpoint was disability, as measured by the Modified Rankin Scale (mRS) score at 90 days.

The study was started in China with the intention of expanding recruitment internationally. The planned enrollment was more than 2,000 patients.

However, in March of 2022, after 821 patients had been enrolled, the data safety monitoring board (DSMB) recommended that recruitment into the trial be suspended because of a safety signal. All of the patients who had been recruited were from China.

These patients were followed to obtain the 3-month outcome results, after which the DSMB recommended that the trial be stopped because safety was still a problem.

Mean systolic blood pressure was 125 mm Hg at 1 hour and 121 mm Hg at 24 hours in the more intensive-treatment group; it was 143 mm Hg at 1 hour and 139 mm Hg at 24 hours in the less intensive-treatment group, giving an adjusted mean difference over 24 hours of 18 mm Hg.
 

Worse disability scores

Results showed that the patients who underwent the more intensive blood pressure lowering had more disability at 3-month follow-up, with worse scores on a shift analysis of the mRS than those in the less intensive group (common odds ratio, 1.37; 95% confidence interval, 1.07-1.76).

The unfavorable shift in mRS scores in the more intensive group was consistent in adjusted sensitivity analysis, and there was no significant heterogeneity in the treatment effect on the primary outcome across all prespecified subgroups.

The incidence of death or neurologic deterioration at 7 days was higher in the more intensive-treatment group than the less intensive-treatment group (common OR, 1.53), and a between-group difference emerged at 24 hours.

The incidence of death or disability (mRS scores, 3-6) at 90 days was higher among patients in the more intensive-treatment group than the less intensive-treatment group (53% vs. 39%; OR, 1.85; P = .0001).

Among those who survived, more patients in the more intensive-treatment group had major disability (mRS scores, 3-5) at 90 days than did patients in the less intensive-treatment group (43% vs. 28%; OR, 2.07; P = .0001).
 

No difference in ICH or severe hypotension episodes

The incidence of symptomatic intracranial hemorrhage, mortality, and serious adverse events did not significantly differ between the two groups. There were no significant differences in recurrent ischemic stroke events at 90 days, and no episodes of severe hypotension were reported as a serious adverse event.

“Our results show that intensive lowering of blood pressure appears to be associated with worsening physical disability. While there was no difference in mortality rates between the two groups, the lower blood pressure appeared to compromise the ability to recover from the stroke,” Dr. Anderson said.

On the possible mechanism of harm, he suggested that the intensive blood pressure reduction might be interfering with blood flow through the injured part of the brain and impeding the ability to recover from the clot removal procedure.
 

What levels should be aimed for?

Dr. Anderson stressed that it was important to have conducted this trial.

“Current guidelines recommend very conservative level of blood pressure in acute ischemic stroke patients – to below 180 mm Hg. But no lower limit is recommended.

“Most clinicians aim for about the 140 mm Hg mark, but there is a large variation in opinion on what to do,” he said. “Some doctors treat aggressively, believing that lower pressures could be beneficial in preventing bleeding and swelling, and others prefer to keep levels higher. Our results have helped to give some guidance on this.”

Asked what he thought an optimum target would be, Dr. Anderson replied: “For now, I think a target of around 140 mm Hg systolic would be reasonable, and there is no evidence to move below that.”

Yvo Roos, MD, professor of acute neurology at University Medical Center, Amsterdam, a co-author of the ENCHANTED2/MT trial, also commented: “The real importance of these study results is that they show that lowering blood pressure too much is detrimental on outcome. My personal interpretation, looking at the results of this study but also on the previous studies, is that we should aim for a target of 140-150 mm Hg. This is true for patients with recanalization therapy. For patients without any therapy, I would even be more careful in lowering blood pressure and recommend just staying below 180 mm Hg.”

As to whether these results are generalizable to other populations, given that the patients were Chinese, Dr. Anderson noted that Asian people have higher rates of intracranial atherosclerosis and more blood pressure complications in the heart and kidney than White patients. Stroke management patterns also differ.

“These points raise questions about generalizability, and while I think this is an issue for consideration, I do not think it should detract from the clarity of these results,” he commented.

The study is supported by grants from the Shanghai Hospital Development Center, the National Health and Medical Research Council of Australia, the China Stroke Prevention Project, Shanghai Changhai Hospital, the Science and Technology Commission of Shanghai Municipality, Takeda China, Genesis Medtech, and Penumbra. Dr. Anderson has received grants from the National Health and Medical Research Council and Medical Research Futures Fund of Australia, the UK Medical Research Council, Penumbra, and Takeda China.

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

A large randomized trial that was investigating intensive lowering of blood pressure in acute ischemic stroke patients who had undergone mechanical thrombectomy has been stopped early because of safety concerns.

“Intensive control of systolic blood pressure to lower than 120 mm Hg should be avoided to prevent compromising the functional recovery of patients who have received endovascular thrombectomy for acute ischemic stroke due to intracranial large-vessel occlusion,” the investigators conclude.

Results from the ENCHANTED2/MT trial were presented by Craig Anderson, MD, professor of neurology and epidemiology, University of New South Wales, Sydney, during the 14th World Stroke Congress (WSC) in Singapore.

The study was simultaneously published online in The Lancet.

“What our results have pretty convincingly shown is that in acute stroke patients who have undergone mechanical thrombectomy, lowering blood pressure down to a systolic of 120 mm Hg for 3 days is too low for too long. We shouldn’t go that far down,” Dr. Anderson said in an interview.

Dr. Anderson said the trial has provided an important message for clinical practice.

“This result is not what we expected, but it is a definitive result and gives us a lower safety margin for blood pressure in acute ischemic stroke patients. This, in itself, is a big step forward.”

He noted that the optimum blood pressure for these patients is not known.

“We need to do further trials to determine optimum blood pressure in these acute patients, but perhaps we should be aiming more towards 140 mm Hg,” he suggested.

“But this trial shows us that in patients who have had successful clot retrieval with endovascular treatment for acute ischemic stroke, careful blood pressure management is important to avoid levels becoming too low. We have to make sure we don’t overshoot down to 120 mm Hg or below.”

The chair of the WSC session at which the trial was presented, Jeyaraj Pandian, MD, head of neurology at Christian Medical College, Ludhiana, India, who is the current vice-president of the World Stroke Organization, said: “This is a very important result. It has major practical implications.”

As background, Dr. Anderson explained that elevated blood pressure is very common in patients who have an acute ischemic stroke, and the higher the blood pressure, the higher the chances of having a worse outcome.

“Theoretically, if we can control the blood pressure, we may be able to improve outcomes,” he said.

In 2019, the first ENCHANTED trial reported that controlling blood pressure by a moderate amount – to around 140 mm Hg, which is lower than currently recommended in the guidelines – was linked to a reduction in bleeding complications of thrombolysis and appeared safe, but it did not improve recovery, Dr. Anderson noted.

“This trial was done before mechanical thrombectomy became routinely adopted, and this procedure has now become the standard of care for large-vessel occlusion strokes, but we don’t know what we should do about blood pressure in these patients,” he added.

A smaller French trial has suggested lowering blood pressure to 130 mm Hg, rather than a more liberal 130-180 mm Hg, was safe after successful mechanical thrombectomy, but there was no effect on functional outcome.

“In stroke patients with a large-vessel occlusion, blood pressure is often elevated to very high levels. There are wide ranges of opinions on what to do about this – whether it should be lowered, and by how much,” Dr. Anderson said. “We conducted the current ENCHANTED2/MT trial to look at this issue.”

The trial randomly assigned patients who had undergone successful mechanical clot retrieval and reperfusion but whose blood pressure was still elevated to two groups. In one group, blood pressure was aggressively lowered to less than 120 mm Hg within 1 hour of reperfusion, and blood pressure was kept at this level for 3 days. In the other group, a more liberal approach was used: Blood pressure was kept at 140-180 mm Hg.

The primary endpoint was disability, as measured by the Modified Rankin Scale (mRS) score at 90 days.

The study was started in China with the intention of expanding recruitment internationally. The planned enrollment was more than 2,000 patients.

However, in March of 2022, after 821 patients had been enrolled, the data safety monitoring board (DSMB) recommended that recruitment into the trial be suspended because of a safety signal. All of the patients who had been recruited were from China.

These patients were followed to obtain the 3-month outcome results, after which the DSMB recommended that the trial be stopped because safety was still a problem.

Mean systolic blood pressure was 125 mm Hg at 1 hour and 121 mm Hg at 24 hours in the more intensive-treatment group; it was 143 mm Hg at 1 hour and 139 mm Hg at 24 hours in the less intensive-treatment group, giving an adjusted mean difference over 24 hours of 18 mm Hg.
 

Worse disability scores

Results showed that the patients who underwent the more intensive blood pressure lowering had more disability at 3-month follow-up, with worse scores on a shift analysis of the mRS than those in the less intensive group (common odds ratio, 1.37; 95% confidence interval, 1.07-1.76).

The unfavorable shift in mRS scores in the more intensive group was consistent in adjusted sensitivity analysis, and there was no significant heterogeneity in the treatment effect on the primary outcome across all prespecified subgroups.

The incidence of death or neurologic deterioration at 7 days was higher in the more intensive-treatment group than the less intensive-treatment group (common OR, 1.53), and a between-group difference emerged at 24 hours.

The incidence of death or disability (mRS scores, 3-6) at 90 days was higher among patients in the more intensive-treatment group than the less intensive-treatment group (53% vs. 39%; OR, 1.85; P = .0001).

Among those who survived, more patients in the more intensive-treatment group had major disability (mRS scores, 3-5) at 90 days than did patients in the less intensive-treatment group (43% vs. 28%; OR, 2.07; P = .0001).
 

No difference in ICH or severe hypotension episodes

The incidence of symptomatic intracranial hemorrhage, mortality, and serious adverse events did not significantly differ between the two groups. There were no significant differences in recurrent ischemic stroke events at 90 days, and no episodes of severe hypotension were reported as a serious adverse event.

“Our results show that intensive lowering of blood pressure appears to be associated with worsening physical disability. While there was no difference in mortality rates between the two groups, the lower blood pressure appeared to compromise the ability to recover from the stroke,” Dr. Anderson said.

On the possible mechanism of harm, he suggested that the intensive blood pressure reduction might be interfering with blood flow through the injured part of the brain and impeding the ability to recover from the clot removal procedure.
 

What levels should be aimed for?

Dr. Anderson stressed that it was important to have conducted this trial.

“Current guidelines recommend very conservative level of blood pressure in acute ischemic stroke patients – to below 180 mm Hg. But no lower limit is recommended.

“Most clinicians aim for about the 140 mm Hg mark, but there is a large variation in opinion on what to do,” he said. “Some doctors treat aggressively, believing that lower pressures could be beneficial in preventing bleeding and swelling, and others prefer to keep levels higher. Our results have helped to give some guidance on this.”

Asked what he thought an optimum target would be, Dr. Anderson replied: “For now, I think a target of around 140 mm Hg systolic would be reasonable, and there is no evidence to move below that.”

Yvo Roos, MD, professor of acute neurology at University Medical Center, Amsterdam, a co-author of the ENCHANTED2/MT trial, also commented: “The real importance of these study results is that they show that lowering blood pressure too much is detrimental on outcome. My personal interpretation, looking at the results of this study but also on the previous studies, is that we should aim for a target of 140-150 mm Hg. This is true for patients with recanalization therapy. For patients without any therapy, I would even be more careful in lowering blood pressure and recommend just staying below 180 mm Hg.”

As to whether these results are generalizable to other populations, given that the patients were Chinese, Dr. Anderson noted that Asian people have higher rates of intracranial atherosclerosis and more blood pressure complications in the heart and kidney than White patients. Stroke management patterns also differ.

“These points raise questions about generalizability, and while I think this is an issue for consideration, I do not think it should detract from the clarity of these results,” he commented.

The study is supported by grants from the Shanghai Hospital Development Center, the National Health and Medical Research Council of Australia, the China Stroke Prevention Project, Shanghai Changhai Hospital, the Science and Technology Commission of Shanghai Municipality, Takeda China, Genesis Medtech, and Penumbra. Dr. Anderson has received grants from the National Health and Medical Research Council and Medical Research Futures Fund of Australia, the UK Medical Research Council, Penumbra, and Takeda China.

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

A new study based on U.S. veterans’ medical records adds to the evidence for a link between gout – especially poorly controlled cases – and cardiovascular disease (CVD) risk, Tate Johnson, MD, reported at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network.

Gout was associated with a 68% increased risk of heart failure (HF) hospitalization, 25% increased risk of HF-related death, and a 22% increased risk of major adverse cardiovascular events (MACE), said Dr. Johnson, of the division of rheumatology at the University of Nebraska, Omaha.

Poorly controlled serum urate was associated with a higher risk of cardiovascular events, regardless of the use of urate-lowering therapy (ULT). He said more research is needed to see if there is a causal link between gout, hyperuricemia – or its treatment – and CVD risk.

Dr. Johnson and colleagues used records from the Veterans Health Administration for this study. They created a retrospective, matched cohort study that looked at records dating from January 1999 to September 2015. Patients with gout (≥ 2 ICD-9 codes) were matched 1:10 on age, sex, and year of VHA enrollment to patients without a gout ICD-9 code or a record of receiving ULT. They matched 559,243 people with gout to 5,407,379 people who did not have a diagnosis or a recorded treatment for this condition.

Over 43,331,604 person-years, Dr. Johnson and colleagues observed 137,162 CVD events in gout (incidence rate 33.96 per 1,000 person-years) vs. 879,903 in non-gout patients (IR 22.37 per 1,000 person-years). Gout was most strongly associated with HF hospitalization, with a nearly threefold higher risk (hazard ratio, 2.78; 95% confidence interval, 2.73-2.83), which attenuated but persisted after adjustment for additional CVD risk factors (adjusted hazard ratio, 1.68; 95% CI, 1.65-1.70) and excluding patients with prevalent HF (aHR, 1.60; 95% CI, 1.57-1.64).

People with gout were also at higher risk of HF-related death (aHR, 1.25; 95% CI, 1.21-1.29), MACE (aHR, 1.22; 95% CI, 1.21-1.23), and coronary artery disease–related death (aHR, 1.21; 95% CI, 1.20-1.22).

Among people with gout in the study, poor serum urate control was associated with a higher risk of all CVD events, with the highest CVD risk occurring in patients with inadequately controlled serum urate despite receipt of ULT, particularly related to HF hospitalization (aHR, 1.43; 95% CI, 1.34-1.52) and HF-related death (aHR, 1.47; 95% CI, 1.34-1.61).

Limits of the study include the generalizability of the study population. Reflecting the VHA’s patient population, 99% of the cohort were men, with 62% of the gout group and 59.4% of the control group identifying as White and non-Hispanic.

The study provides evidence that may be found only by studying medical records, Richard J. Johnson, MD, of the University of Colorado at Denver, Aurora, said in an interview.

Dr. Richard Johnson, who is not related to the author, said that only about one-third of people with gout are adequately treated, and about another one-third take urate-lowering therapy (ULT) but fail to get their serum urate level under control. But it would be unethical to design a clinical trial to study CVD risk and poorly controlled serum urate without ULT treatment.

“The only way you can figure out if uric acid lowering is going to help these guys is to actually do a study like this where you see the ones who don’t get adequate treatment versus adequate treatment and you show that there’s going to be a difference in outcome,” he said.

Dr. Richard Johnson contrasted this approach with the one used in the recently reported study that appeared to cast doubt on the link between serum uric acid levels and cardiovascular disease. The ALL-HEART trial found that allopurinol, a drug commonly used to treat gout, provided no benefit in terms of reducing cardiovascular events in patients with ischemic heart disease. But these patients did not have gout, and that was a critical difference, he said.

He noted that it was not surprising that the results of ALL-HEART were negative, given the study design.

“The ALL-HEART study treated people regardless of their uric acid level, and they also excluded subjects who had a history of gout,” he said. “Yet the risk associated with uric acid occurs primarily among those with elevated serum uric acid levels and those with gout.”

The study received funding from the Rheumatology Research Foundation and the VHA. Neither Dr. Tate Johnson nor Dr. Richard Johnson had any relevant disclosures.

A new study based on U.S. veterans’ medical records adds to the evidence for a link between gout – especially poorly controlled cases – and cardiovascular disease (CVD) risk, Tate Johnson, MD, reported at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network.

Gout was associated with a 68% increased risk of heart failure (HF) hospitalization, 25% increased risk of HF-related death, and a 22% increased risk of major adverse cardiovascular events (MACE), said Dr. Johnson, of the division of rheumatology at the University of Nebraska, Omaha.

Poorly controlled serum urate was associated with a higher risk of cardiovascular events, regardless of the use of urate-lowering therapy (ULT). He said more research is needed to see if there is a causal link between gout, hyperuricemia – or its treatment – and CVD risk.

Dr. Johnson and colleagues used records from the Veterans Health Administration for this study. They created a retrospective, matched cohort study that looked at records dating from January 1999 to September 2015. Patients with gout (≥ 2 ICD-9 codes) were matched 1:10 on age, sex, and year of VHA enrollment to patients without a gout ICD-9 code or a record of receiving ULT. They matched 559,243 people with gout to 5,407,379 people who did not have a diagnosis or a recorded treatment for this condition.

Over 43,331,604 person-years, Dr. Johnson and colleagues observed 137,162 CVD events in gout (incidence rate 33.96 per 1,000 person-years) vs. 879,903 in non-gout patients (IR 22.37 per 1,000 person-years). Gout was most strongly associated with HF hospitalization, with a nearly threefold higher risk (hazard ratio, 2.78; 95% confidence interval, 2.73-2.83), which attenuated but persisted after adjustment for additional CVD risk factors (adjusted hazard ratio, 1.68; 95% CI, 1.65-1.70) and excluding patients with prevalent HF (aHR, 1.60; 95% CI, 1.57-1.64).

People with gout were also at higher risk of HF-related death (aHR, 1.25; 95% CI, 1.21-1.29), MACE (aHR, 1.22; 95% CI, 1.21-1.23), and coronary artery disease–related death (aHR, 1.21; 95% CI, 1.20-1.22).

Among people with gout in the study, poor serum urate control was associated with a higher risk of all CVD events, with the highest CVD risk occurring in patients with inadequately controlled serum urate despite receipt of ULT, particularly related to HF hospitalization (aHR, 1.43; 95% CI, 1.34-1.52) and HF-related death (aHR, 1.47; 95% CI, 1.34-1.61).

Limits of the study include the generalizability of the study population. Reflecting the VHA’s patient population, 99% of the cohort were men, with 62% of the gout group and 59.4% of the control group identifying as White and non-Hispanic.

The study provides evidence that may be found only by studying medical records, Richard J. Johnson, MD, of the University of Colorado at Denver, Aurora, said in an interview.

Dr. Richard Johnson, who is not related to the author, said that only about one-third of people with gout are adequately treated, and about another one-third take urate-lowering therapy (ULT) but fail to get their serum urate level under control. But it would be unethical to design a clinical trial to study CVD risk and poorly controlled serum urate without ULT treatment.

“The only way you can figure out if uric acid lowering is going to help these guys is to actually do a study like this where you see the ones who don’t get adequate treatment versus adequate treatment and you show that there’s going to be a difference in outcome,” he said.

Dr. Richard Johnson contrasted this approach with the one used in the recently reported study that appeared to cast doubt on the link between serum uric acid levels and cardiovascular disease. The ALL-HEART trial found that allopurinol, a drug commonly used to treat gout, provided no benefit in terms of reducing cardiovascular events in patients with ischemic heart disease. But these patients did not have gout, and that was a critical difference, he said.

He noted that it was not surprising that the results of ALL-HEART were negative, given the study design.

“The ALL-HEART study treated people regardless of their uric acid level, and they also excluded subjects who had a history of gout,” he said. “Yet the risk associated with uric acid occurs primarily among those with elevated serum uric acid levels and those with gout.”

The study received funding from the Rheumatology Research Foundation and the VHA. Neither Dr. Tate Johnson nor Dr. Richard Johnson had any relevant disclosures.

A new study based on U.S. veterans’ medical records adds to the evidence for a link between gout – especially poorly controlled cases – and cardiovascular disease (CVD) risk, Tate Johnson, MD, reported at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network.

Gout was associated with a 68% increased risk of heart failure (HF) hospitalization, 25% increased risk of HF-related death, and a 22% increased risk of major adverse cardiovascular events (MACE), said Dr. Johnson, of the division of rheumatology at the University of Nebraska, Omaha.

Poorly controlled serum urate was associated with a higher risk of cardiovascular events, regardless of the use of urate-lowering therapy (ULT). He said more research is needed to see if there is a causal link between gout, hyperuricemia – or its treatment – and CVD risk.

Dr. Johnson and colleagues used records from the Veterans Health Administration for this study. They created a retrospective, matched cohort study that looked at records dating from January 1999 to September 2015. Patients with gout (≥ 2 ICD-9 codes) were matched 1:10 on age, sex, and year of VHA enrollment to patients without a gout ICD-9 code or a record of receiving ULT. They matched 559,243 people with gout to 5,407,379 people who did not have a diagnosis or a recorded treatment for this condition.

Over 43,331,604 person-years, Dr. Johnson and colleagues observed 137,162 CVD events in gout (incidence rate 33.96 per 1,000 person-years) vs. 879,903 in non-gout patients (IR 22.37 per 1,000 person-years). Gout was most strongly associated with HF hospitalization, with a nearly threefold higher risk (hazard ratio, 2.78; 95% confidence interval, 2.73-2.83), which attenuated but persisted after adjustment for additional CVD risk factors (adjusted hazard ratio, 1.68; 95% CI, 1.65-1.70) and excluding patients with prevalent HF (aHR, 1.60; 95% CI, 1.57-1.64).

People with gout were also at higher risk of HF-related death (aHR, 1.25; 95% CI, 1.21-1.29), MACE (aHR, 1.22; 95% CI, 1.21-1.23), and coronary artery disease–related death (aHR, 1.21; 95% CI, 1.20-1.22).

Among people with gout in the study, poor serum urate control was associated with a higher risk of all CVD events, with the highest CVD risk occurring in patients with inadequately controlled serum urate despite receipt of ULT, particularly related to HF hospitalization (aHR, 1.43; 95% CI, 1.34-1.52) and HF-related death (aHR, 1.47; 95% CI, 1.34-1.61).

Limits of the study include the generalizability of the study population. Reflecting the VHA’s patient population, 99% of the cohort were men, with 62% of the gout group and 59.4% of the control group identifying as White and non-Hispanic.

The study provides evidence that may be found only by studying medical records, Richard J. Johnson, MD, of the University of Colorado at Denver, Aurora, said in an interview.

Dr. Richard Johnson, who is not related to the author, said that only about one-third of people with gout are adequately treated, and about another one-third take urate-lowering therapy (ULT) but fail to get their serum urate level under control. But it would be unethical to design a clinical trial to study CVD risk and poorly controlled serum urate without ULT treatment.

“The only way you can figure out if uric acid lowering is going to help these guys is to actually do a study like this where you see the ones who don’t get adequate treatment versus adequate treatment and you show that there’s going to be a difference in outcome,” he said.

Dr. Richard Johnson contrasted this approach with the one used in the recently reported study that appeared to cast doubt on the link between serum uric acid levels and cardiovascular disease. The ALL-HEART trial found that allopurinol, a drug commonly used to treat gout, provided no benefit in terms of reducing cardiovascular events in patients with ischemic heart disease. But these patients did not have gout, and that was a critical difference, he said.

He noted that it was not surprising that the results of ALL-HEART were negative, given the study design.

“The ALL-HEART study treated people regardless of their uric acid level, and they also excluded subjects who had a history of gout,” he said. “Yet the risk associated with uric acid occurs primarily among those with elevated serum uric acid levels and those with gout.”

The study received funding from the Rheumatology Research Foundation and the VHA. Neither Dr. Tate Johnson nor Dr. Richard Johnson had any relevant disclosures.

Patients with acute ischemic stroke presenting late at the hospital can be selected for endovascular thrombectomy by the presence of collateral flow on CT angiography (CTA), a new study shows.

The MR CLEAN-LATE trial found that patients selected for thrombectomy in this way had a greater chance of a better functional outcome than patients who did not receive endovascular therapy.

The study was presented at the 14th World Stroke Congress in Singapore by study investigator Susanne Olthuis, MD, of Maastricht (the Netherlands) University Medical Center.

Patients in the intervention group were more likely to show a benefit on the primary endpoint of modified Rankin Scale (mRS) score at 90 days with a significant common odds ratio of 1.68, a finding that received applause from attendees of the plenary WSC session at which the study was presented.

“This means that patients treated with endovascular therapy in this trial had about a 1.7 times higher chance of achieving a better functional outcome at 90 days,” Dr. Olthuis said.

“Selection based on collateral flow identifies an additional group of patients eligible for late-window endovascular therapy in addition to those eligible based on perfusion and clinical criteria,” Dr. Olthuis concluded.

“We recommend implementation of collateral selection in routine clinical practice as it is time efficient. The CTA is already available, and it involves a low-complexity assessment. The only distinction that needs to be made is whether or not there are any collaterals visible on CTA. If collaterals are absent or there is any doubt, then CT perfusion [CTP] imaging can still be used,” she added.

Co–principal investigator Wim H. van Zwam, MD, interventional radiologist at Maastricht, said in a comment:“My take-home message is that now in the late window we can select patients based on the presence of collaterals on CT angiography, which makes selection easier and faster and more widely available.

“If any collaterals are seen – and that is easily done just by looking at the CTA scan – then the patient can be selected for endovascular treatment,” Dr. van Zwam added. “We don’t need to wait for calculations of core and penumbra volumes from the CTP scan. There will also be additional patients who can benefit from endovascular therapy who do not fulfill the CTP criteria but do have visible collaterals.”

Explaining the background to the study, Dr. Olthuis noted that endovascular thrombectomy for large vessel occlusion stroke is safe and effective if performed within 6 hours and the effect then diminishes over time. In the original trial of endovascular treatment, MR CLEAN, patients with higher collateral grades had more treatment benefit, leading to the hypothesis that the assessment of collateral blood flow could help identify patients who would still benefit in the late time window.

The current MR CLEAN-LATE trial therefore set out to compare safety and efficacy of endovascular therapy in patients with acute ischemic stroke in the anterior circulation presenting within 6-24 hours from symptom onset with patients selected based on the presence of collateral flow on CTA.

At the time the trial was starting, the DAWN and DEFUSE 3 trials reported showing benefit of endovascular therapy in patients presenting in the late window who had been selected for endovascular treatment based on a combination of perfusion imaging and clinical criteria, so patients who fitted these criteria were also excluded from MR CLEAN-LATE as they would now be eligible for endovascular therapy under the latest clinical guidelines. 

But the study continued, as “we believed collateral selection may still be able to identify an additional group of patients that may benefit from endovascular therapy in the late window,” Dr. Olthuis said.

The trial randomly assigned 502 such patients with a National Institutes of Health Stroke Scale (NIHSS) score of at least 2 and with collateral flow grades of 1-3 to receive endovascular therapy (intervention) or control.

Safety data showed a slightly but nonsignificantly higher mortality rate at 90 days in the control group (30%) versus 24% in the intervention group.

The rate of symptomatic intracranial hemorrhage was higher in the intervention group (6.7%) versus 1.6% in the control group, but Dr. Olthuis pointed out that the rate of sICH in the intervention group was similar to that in the endovascular groups of the DAWN and DEFUSE 3 trials.

The primary endpoint – mRS score at 90 days – showed a shift toward better outcome in the intervention group, with an adjusted common OR of 1.68 (95% confidence interval, 1.21-2.33).

The median mRS score in the intervention group was 3 (95% CI, 2-5) versus 4 (95% CI, 2-6) in the control group.

Secondary outcomes also showed benefits for the intervention group for the endpoints of mRS score 0-1 versus 2-6 (OR, 1.63); mRS 0-2 versus 3-6 (OR 1.54); and mRS 0-3 versus 4-6 (OR, 1.74).

In addition, NIHSS score was reduced by 17% at 24 hours and by 27% by 5-7 days or discharge in the intervention group. Recanalization at 24 hours was also improved in the intervention group (81% vs. 52%) and infarct size was reduced by 32%.

Dr. Olthuis explained that collateral grade was defined as the amount of collateral flow in the affected hemisphere as a percentage of the contralateral site, with grade 0 correlating to an absence of collaterals (and these were the only patients excluded).

Grade 1 included patients with 50% or less collaterals, grade 2 more than 50%, and grade 3 excellent collaterals – around 100%. “We included grade 1, 2 and 3, and subgroup analysis suggested no treatment interactions between different collateral grades in the patients included,” she said.

Dr. van Zwam noted that there has been evidence from other studies suggesting that the presence of collateral flow could be used to select patients for late thrombectomy, but MR CLEAN-LATE is the first randomized trial to show this and provides confirmation that this strategy is valid.

“Our results show that patients can be selected with just standard CT angiography imaging and that CT perfusion is not necessary. This will make it easier and faster to select patients especially for centers in low-resource areas who do not yet have CT perfusion imaging,” he commented.

“But even in centers where CT perfusion imaging is performed, these results should mean that we do not have to wait to analyze these results before going ahead with thrombectomy. It will also give us an additional tool, as some patients do not meet the criteria on perfusion imaging but still have identifiable collaterals and thus would now qualify for endovascular thrombectomy,” he added.
 

Could collateral assessment replace CT perfusion?

Commenting on the MR CLEAN-LATE trial, Stefan Kiechl, MD, Medical University of Innsbruck (Austria), who is cochair of the WSC scientific committee, said it was an “excellent study.”

“This study does not rely on advanced imaging (e.g., mismatch) and criteria can easily be interpreted on CT/CTA. If the study is published and all details are available this study may substantially ease endovascular therapy in the late time window,” Dr. Kiechl told this news organization.

Also commenting, Urs Fischer, MD, chairman of the department of neurology at the University Hospital Basel (Switzerland), who was not involved with MR CLEAN-LATE, said: “This is another study that has nicely shown that endovascular therapy in patients in the later time window is highly effective.”

Dr. Fischer said he was not surprised by the results. 

“I was expecting the trial to be positive,” he said. “What we can say is that endovascular therapy in patients with proximal vessel occlusion is a very effective intervention – probably one of the most important interventions in the history of medicine – and now we have another subgroup to whom we can offer this therapy. So, this is an important study that will improve the outcome of many further patients.”

Yvo Roos, MD, professor of acute neurology at University Medical Center, Amsterdam, who was a MR CLEAN-LATE investigator, agreed that the trial has the potential to increase number of patients who can be treated with endovascular therapy.

But both Dr. Roos and Dr. Fischer were not convinced that collateral assessment would replace CT perfusion as the first-line choice in selecting patients for endovascular treatment.

“We need to see what kind of patients were included in the trial and what kind of perfusion imaging characteristics they had, to see how they compare with patients selected by perfusion imaging,” Dr. Roos noted. “I think CT perfusion is here. But if the data shows that collateral score is better able to identify patients for endovascular treatment than CT perfusion, then this has the potential to change practice. But that needs to be shown.”

All patients screened for the MR CLEAN-LATE trial also received CT perfusion imaging as part of the standard imaging protocol, and many were selected for endovascular therapy directly on this basis, so would not have entered the trial. The researchers plan to analyze these results and to compare how the two approaches differ.

MR CLEAN-LATE is an investigator-driven study, funded by the Dutch Heart Foundation, the Brain Foundation Netherlands, and Medtronic. The study was designed and conducted, analyzed, and interpreted by the investigators independently of all sponsors. Dr. Olthuis reported no relevant financial relationships.

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

Patients with acute ischemic stroke presenting late at the hospital can be selected for endovascular thrombectomy by the presence of collateral flow on CT angiography (CTA), a new study shows.

The MR CLEAN-LATE trial found that patients selected for thrombectomy in this way had a greater chance of a better functional outcome than patients who did not receive endovascular therapy.

The study was presented at the 14th World Stroke Congress in Singapore by study investigator Susanne Olthuis, MD, of Maastricht (the Netherlands) University Medical Center.

Patients in the intervention group were more likely to show a benefit on the primary endpoint of modified Rankin Scale (mRS) score at 90 days with a significant common odds ratio of 1.68, a finding that received applause from attendees of the plenary WSC session at which the study was presented.

“This means that patients treated with endovascular therapy in this trial had about a 1.7 times higher chance of achieving a better functional outcome at 90 days,” Dr. Olthuis said.

“Selection based on collateral flow identifies an additional group of patients eligible for late-window endovascular therapy in addition to those eligible based on perfusion and clinical criteria,” Dr. Olthuis concluded.

“We recommend implementation of collateral selection in routine clinical practice as it is time efficient. The CTA is already available, and it involves a low-complexity assessment. The only distinction that needs to be made is whether or not there are any collaterals visible on CTA. If collaterals are absent or there is any doubt, then CT perfusion [CTP] imaging can still be used,” she added.

Co–principal investigator Wim H. van Zwam, MD, interventional radiologist at Maastricht, said in a comment:“My take-home message is that now in the late window we can select patients based on the presence of collaterals on CT angiography, which makes selection easier and faster and more widely available.

“If any collaterals are seen – and that is easily done just by looking at the CTA scan – then the patient can be selected for endovascular treatment,” Dr. van Zwam added. “We don’t need to wait for calculations of core and penumbra volumes from the CTP scan. There will also be additional patients who can benefit from endovascular therapy who do not fulfill the CTP criteria but do have visible collaterals.”

Explaining the background to the study, Dr. Olthuis noted that endovascular thrombectomy for large vessel occlusion stroke is safe and effective if performed within 6 hours and the effect then diminishes over time. In the original trial of endovascular treatment, MR CLEAN, patients with higher collateral grades had more treatment benefit, leading to the hypothesis that the assessment of collateral blood flow could help identify patients who would still benefit in the late time window.

The current MR CLEAN-LATE trial therefore set out to compare safety and efficacy of endovascular therapy in patients with acute ischemic stroke in the anterior circulation presenting within 6-24 hours from symptom onset with patients selected based on the presence of collateral flow on CTA.

At the time the trial was starting, the DAWN and DEFUSE 3 trials reported showing benefit of endovascular therapy in patients presenting in the late window who had been selected for endovascular treatment based on a combination of perfusion imaging and clinical criteria, so patients who fitted these criteria were also excluded from MR CLEAN-LATE as they would now be eligible for endovascular therapy under the latest clinical guidelines. 

But the study continued, as “we believed collateral selection may still be able to identify an additional group of patients that may benefit from endovascular therapy in the late window,” Dr. Olthuis said.

The trial randomly assigned 502 such patients with a National Institutes of Health Stroke Scale (NIHSS) score of at least 2 and with collateral flow grades of 1-3 to receive endovascular therapy (intervention) or control.

Safety data showed a slightly but nonsignificantly higher mortality rate at 90 days in the control group (30%) versus 24% in the intervention group.

The rate of symptomatic intracranial hemorrhage was higher in the intervention group (6.7%) versus 1.6% in the control group, but Dr. Olthuis pointed out that the rate of sICH in the intervention group was similar to that in the endovascular groups of the DAWN and DEFUSE 3 trials.

The primary endpoint – mRS score at 90 days – showed a shift toward better outcome in the intervention group, with an adjusted common OR of 1.68 (95% confidence interval, 1.21-2.33).

The median mRS score in the intervention group was 3 (95% CI, 2-5) versus 4 (95% CI, 2-6) in the control group.

Secondary outcomes also showed benefits for the intervention group for the endpoints of mRS score 0-1 versus 2-6 (OR, 1.63); mRS 0-2 versus 3-6 (OR 1.54); and mRS 0-3 versus 4-6 (OR, 1.74).

In addition, NIHSS score was reduced by 17% at 24 hours and by 27% by 5-7 days or discharge in the intervention group. Recanalization at 24 hours was also improved in the intervention group (81% vs. 52%) and infarct size was reduced by 32%.

Dr. Olthuis explained that collateral grade was defined as the amount of collateral flow in the affected hemisphere as a percentage of the contralateral site, with grade 0 correlating to an absence of collaterals (and these were the only patients excluded).

Grade 1 included patients with 50% or less collaterals, grade 2 more than 50%, and grade 3 excellent collaterals – around 100%. “We included grade 1, 2 and 3, and subgroup analysis suggested no treatment interactions between different collateral grades in the patients included,” she said.

Dr. van Zwam noted that there has been evidence from other studies suggesting that the presence of collateral flow could be used to select patients for late thrombectomy, but MR CLEAN-LATE is the first randomized trial to show this and provides confirmation that this strategy is valid.

“Our results show that patients can be selected with just standard CT angiography imaging and that CT perfusion is not necessary. This will make it easier and faster to select patients especially for centers in low-resource areas who do not yet have CT perfusion imaging,” he commented.

“But even in centers where CT perfusion imaging is performed, these results should mean that we do not have to wait to analyze these results before going ahead with thrombectomy. It will also give us an additional tool, as some patients do not meet the criteria on perfusion imaging but still have identifiable collaterals and thus would now qualify for endovascular thrombectomy,” he added.
 

Could collateral assessment replace CT perfusion?

Commenting on the MR CLEAN-LATE trial, Stefan Kiechl, MD, Medical University of Innsbruck (Austria), who is cochair of the WSC scientific committee, said it was an “excellent study.”

“This study does not rely on advanced imaging (e.g., mismatch) and criteria can easily be interpreted on CT/CTA. If the study is published and all details are available this study may substantially ease endovascular therapy in the late time window,” Dr. Kiechl told this news organization.

Also commenting, Urs Fischer, MD, chairman of the department of neurology at the University Hospital Basel (Switzerland), who was not involved with MR CLEAN-LATE, said: “This is another study that has nicely shown that endovascular therapy in patients in the later time window is highly effective.”

Dr. Fischer said he was not surprised by the results. 

“I was expecting the trial to be positive,” he said. “What we can say is that endovascular therapy in patients with proximal vessel occlusion is a very effective intervention – probably one of the most important interventions in the history of medicine – and now we have another subgroup to whom we can offer this therapy. So, this is an important study that will improve the outcome of many further patients.”

Yvo Roos, MD, professor of acute neurology at University Medical Center, Amsterdam, who was a MR CLEAN-LATE investigator, agreed that the trial has the potential to increase number of patients who can be treated with endovascular therapy.

But both Dr. Roos and Dr. Fischer were not convinced that collateral assessment would replace CT perfusion as the first-line choice in selecting patients for endovascular treatment.

“We need to see what kind of patients were included in the trial and what kind of perfusion imaging characteristics they had, to see how they compare with patients selected by perfusion imaging,” Dr. Roos noted. “I think CT perfusion is here. But if the data shows that collateral score is better able to identify patients for endovascular treatment than CT perfusion, then this has the potential to change practice. But that needs to be shown.”

All patients screened for the MR CLEAN-LATE trial also received CT perfusion imaging as part of the standard imaging protocol, and many were selected for endovascular therapy directly on this basis, so would not have entered the trial. The researchers plan to analyze these results and to compare how the two approaches differ.

MR CLEAN-LATE is an investigator-driven study, funded by the Dutch Heart Foundation, the Brain Foundation Netherlands, and Medtronic. The study was designed and conducted, analyzed, and interpreted by the investigators independently of all sponsors. Dr. Olthuis reported no relevant financial relationships.

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

Patients with acute ischemic stroke presenting late at the hospital can be selected for endovascular thrombectomy by the presence of collateral flow on CT angiography (CTA), a new study shows.

The MR CLEAN-LATE trial found that patients selected for thrombectomy in this way had a greater chance of a better functional outcome than patients who did not receive endovascular therapy.

The study was presented at the 14th World Stroke Congress in Singapore by study investigator Susanne Olthuis, MD, of Maastricht (the Netherlands) University Medical Center.

Patients in the intervention group were more likely to show a benefit on the primary endpoint of modified Rankin Scale (mRS) score at 90 days with a significant common odds ratio of 1.68, a finding that received applause from attendees of the plenary WSC session at which the study was presented.

“This means that patients treated with endovascular therapy in this trial had about a 1.7 times higher chance of achieving a better functional outcome at 90 days,” Dr. Olthuis said.

“Selection based on collateral flow identifies an additional group of patients eligible for late-window endovascular therapy in addition to those eligible based on perfusion and clinical criteria,” Dr. Olthuis concluded.

“We recommend implementation of collateral selection in routine clinical practice as it is time efficient. The CTA is already available, and it involves a low-complexity assessment. The only distinction that needs to be made is whether or not there are any collaterals visible on CTA. If collaterals are absent or there is any doubt, then CT perfusion [CTP] imaging can still be used,” she added.

Co–principal investigator Wim H. van Zwam, MD, interventional radiologist at Maastricht, said in a comment:“My take-home message is that now in the late window we can select patients based on the presence of collaterals on CT angiography, which makes selection easier and faster and more widely available.

“If any collaterals are seen – and that is easily done just by looking at the CTA scan – then the patient can be selected for endovascular treatment,” Dr. van Zwam added. “We don’t need to wait for calculations of core and penumbra volumes from the CTP scan. There will also be additional patients who can benefit from endovascular therapy who do not fulfill the CTP criteria but do have visible collaterals.”

Explaining the background to the study, Dr. Olthuis noted that endovascular thrombectomy for large vessel occlusion stroke is safe and effective if performed within 6 hours and the effect then diminishes over time. In the original trial of endovascular treatment, MR CLEAN, patients with higher collateral grades had more treatment benefit, leading to the hypothesis that the assessment of collateral blood flow could help identify patients who would still benefit in the late time window.

The current MR CLEAN-LATE trial therefore set out to compare safety and efficacy of endovascular therapy in patients with acute ischemic stroke in the anterior circulation presenting within 6-24 hours from symptom onset with patients selected based on the presence of collateral flow on CTA.

At the time the trial was starting, the DAWN and DEFUSE 3 trials reported showing benefit of endovascular therapy in patients presenting in the late window who had been selected for endovascular treatment based on a combination of perfusion imaging and clinical criteria, so patients who fitted these criteria were also excluded from MR CLEAN-LATE as they would now be eligible for endovascular therapy under the latest clinical guidelines. 

But the study continued, as “we believed collateral selection may still be able to identify an additional group of patients that may benefit from endovascular therapy in the late window,” Dr. Olthuis said.

The trial randomly assigned 502 such patients with a National Institutes of Health Stroke Scale (NIHSS) score of at least 2 and with collateral flow grades of 1-3 to receive endovascular therapy (intervention) or control.

Safety data showed a slightly but nonsignificantly higher mortality rate at 90 days in the control group (30%) versus 24% in the intervention group.

The rate of symptomatic intracranial hemorrhage was higher in the intervention group (6.7%) versus 1.6% in the control group, but Dr. Olthuis pointed out that the rate of sICH in the intervention group was similar to that in the endovascular groups of the DAWN and DEFUSE 3 trials.

The primary endpoint – mRS score at 90 days – showed a shift toward better outcome in the intervention group, with an adjusted common OR of 1.68 (95% confidence interval, 1.21-2.33).

The median mRS score in the intervention group was 3 (95% CI, 2-5) versus 4 (95% CI, 2-6) in the control group.

Secondary outcomes also showed benefits for the intervention group for the endpoints of mRS score 0-1 versus 2-6 (OR, 1.63); mRS 0-2 versus 3-6 (OR 1.54); and mRS 0-3 versus 4-6 (OR, 1.74).

In addition, NIHSS score was reduced by 17% at 24 hours and by 27% by 5-7 days or discharge in the intervention group. Recanalization at 24 hours was also improved in the intervention group (81% vs. 52%) and infarct size was reduced by 32%.

Dr. Olthuis explained that collateral grade was defined as the amount of collateral flow in the affected hemisphere as a percentage of the contralateral site, with grade 0 correlating to an absence of collaterals (and these were the only patients excluded).

Grade 1 included patients with 50% or less collaterals, grade 2 more than 50%, and grade 3 excellent collaterals – around 100%. “We included grade 1, 2 and 3, and subgroup analysis suggested no treatment interactions between different collateral grades in the patients included,” she said.

Dr. van Zwam noted that there has been evidence from other studies suggesting that the presence of collateral flow could be used to select patients for late thrombectomy, but MR CLEAN-LATE is the first randomized trial to show this and provides confirmation that this strategy is valid.

“Our results show that patients can be selected with just standard CT angiography imaging and that CT perfusion is not necessary. This will make it easier and faster to select patients especially for centers in low-resource areas who do not yet have CT perfusion imaging,” he commented.

“But even in centers where CT perfusion imaging is performed, these results should mean that we do not have to wait to analyze these results before going ahead with thrombectomy. It will also give us an additional tool, as some patients do not meet the criteria on perfusion imaging but still have identifiable collaterals and thus would now qualify for endovascular thrombectomy,” he added.
 

Could collateral assessment replace CT perfusion?

Commenting on the MR CLEAN-LATE trial, Stefan Kiechl, MD, Medical University of Innsbruck (Austria), who is cochair of the WSC scientific committee, said it was an “excellent study.”

“This study does not rely on advanced imaging (e.g., mismatch) and criteria can easily be interpreted on CT/CTA. If the study is published and all details are available this study may substantially ease endovascular therapy in the late time window,” Dr. Kiechl told this news organization.

Also commenting, Urs Fischer, MD, chairman of the department of neurology at the University Hospital Basel (Switzerland), who was not involved with MR CLEAN-LATE, said: “This is another study that has nicely shown that endovascular therapy in patients in the later time window is highly effective.”

Dr. Fischer said he was not surprised by the results. 

“I was expecting the trial to be positive,” he said. “What we can say is that endovascular therapy in patients with proximal vessel occlusion is a very effective intervention – probably one of the most important interventions in the history of medicine – and now we have another subgroup to whom we can offer this therapy. So, this is an important study that will improve the outcome of many further patients.”

Yvo Roos, MD, professor of acute neurology at University Medical Center, Amsterdam, who was a MR CLEAN-LATE investigator, agreed that the trial has the potential to increase number of patients who can be treated with endovascular therapy.

But both Dr. Roos and Dr. Fischer were not convinced that collateral assessment would replace CT perfusion as the first-line choice in selecting patients for endovascular treatment.

“We need to see what kind of patients were included in the trial and what kind of perfusion imaging characteristics they had, to see how they compare with patients selected by perfusion imaging,” Dr. Roos noted. “I think CT perfusion is here. But if the data shows that collateral score is better able to identify patients for endovascular treatment than CT perfusion, then this has the potential to change practice. But that needs to be shown.”

All patients screened for the MR CLEAN-LATE trial also received CT perfusion imaging as part of the standard imaging protocol, and many were selected for endovascular therapy directly on this basis, so would not have entered the trial. The researchers plan to analyze these results and to compare how the two approaches differ.

MR CLEAN-LATE is an investigator-driven study, funded by the Dutch Heart Foundation, the Brain Foundation Netherlands, and Medtronic. The study was designed and conducted, analyzed, and interpreted by the investigators independently of all sponsors. Dr. Olthuis reported no relevant financial relationships.

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

CINCINNATI – Sickle cell disease is well known for its associated anemia, but patients experience a range of other complications as well. These include vision and kidney problems, delayed growth, susceptibility to infection, and pain.

Another issue, not always as well recognized, is a considerably heightened risk for childhood stroke. “Children with sickle cell disease have 100 times the risk of stroke as other children without sickle cell disease, and there’s also an elevated risk of five times the general population in adults with sickle cell disease,” said Lori Jordan, MD, PhD, in an interview.

At the 2022 annual meeting of the Child Neurology Society, Dr. Jordan spoke about stroke as a complication of sickle cell disease, and the role that neurologists can play in preventing primary or secondary strokes. “At least in children, studies have shown that if we screen and identify patients who are at highest risk of stroke, there are primary prevention therapies – usually implemented by hematologists, but that neurologists often are involved with – both monitoring for cognitive effects of silent cerebral infarct and also with treating patients who unfortunately still have an acute stroke,” said Dr. Jordan, who is an associate professor of pediatrics, neurology, and radiology at Vanderbilt University Medical Center, Nashville, Tenn. She also is director of the pediatric stroke program at Vanderbilt.
 

Time is of the essence

“In general, stroke in children is rare, but it’s more common in sickle cell disease, so it’s really important for providers to know that stroke risk is higher in those patients, particularly in those children, and then identify it and treat it earlier. Time is of the essence, and if we can give them the same therapeutics that we give the general stroke population, then time really becomes a factor, so it’s important that people know that it’s an issue for this population,” said Eboni Lance, MD, PhD, who coordinated the session where Dr. Jordan spoke.

Sickle cell disease is caused by a double mutation in the gene encoding the hemoglobin gene, producing the altered sickle hemoglobin (hemoglobin S). The change causes the hemoglobin proteins to tend to stick to one another, which can lead red blood cells to adopt a sickle-like shape. The sickle-shaped blood cells in turn have a tendency to aggregate and can block blood flow or lead to endothelial injury. Symptoms of stroke in children can include hemiparesis, aphasia, and seizure, but they can also be silent.

If no preventive is employed, one in nine with sickle cell disease will experience a stroke by the age of 19. Cerebrovascular symptoms are the most frequent debilitating complication of the condition. Nearly 40% of patients with sickle cell disease will have a silent cerebral infarct by age 18, as will 50% by age 30. Silent strokes have been associated with worse educational attainment and a greater need for educational special services.

Factors contributing to stroke in children with sickle cell disease include anemia and a low blood oxygen count, reduced oxygen affinity of hemoglobin variant, and cerebral vasculopathy. An estimated 10%-15% of young adults with sickle cell disease have severe intracranial stenosis.
 

Primary and secondary stroke prevention strategies

The dire consequences of stroke in this patient population underline the importance of primary stroke prevention, which requires the use of transcranial Doppler (TCD) ultrasound. It has been validated as a tool to screen for initial stroke risk in children with no history of stroke. High velocity measured on TCD indicates a narrowed blood vessel or elevated blood that is compensating for anemia. It adds up to a “struggling brain,” said Dr. Jordan, during her talk. If the TCD ultrasound velocity is greater than 200 cm/sec (or 170 cm/sec, depending on nonimaging versus imaging TCD), the TWiTCH trial showed that seven monthly transfusions is the number needed to treat to prevent one stroke. After 1 year, patients can be switched from transfusions to hydroxyurea if the patient has no significant intracranial stenosis. Hydroxyurea boosts both fetal and total hemoglobin, and also counters inflammation.

Following an acute stroke or transient ischemic attack, patients should receive a transfusion within 2 hours of presenting in the health care setting. American Society of Hematology guidelines recommend exchange transfusion rather than a simple transfusion. A simple transfusion can be initiated if an exchange transfusion is not available within 2 hours and hemoglobin values are less than 8.5 g/dL, to be followed by performance of exchange transfusion when available.

For chronic secondary stroke prevention, transfusions should be performed approximately monthly with the goal of maintaining hemoglobin above 9 g/dL at all times, as well as suppressing hemoglobin S levels to 30% or less of total hemoglobin.

Sudden, severe headache is a potential harbinger of complications like aneurysm, which occurs 10-fold more often among patients with sickle cell disease than the general population. It could also indicate increased intracranial pressure or cerebral venous sinus thrombosis.

Treatment of acute headache in sickle cell disease should avoid use of triptans, since vasoconstriction can counter the increased cerebral blood flow that compensates for anemia. Gabapentin and amitriptyline are good treatment choices.

New-onset seizures are a potential sign of stroke or posterior reversible leukoencephalopathy (PRES) in patients with sickle cell disease. Urgent MRI should be considered for all new-onset seizures. If blood pressure is high, PRES may be present. Seizures may also be an indicator of a previous brain injury.

Dr. Jordan has no relevant financial disclosures. Dr. Lance has served on an advisory board for Novartis.
 

CINCINNATI – Sickle cell disease is well known for its associated anemia, but patients experience a range of other complications as well. These include vision and kidney problems, delayed growth, susceptibility to infection, and pain.

Another issue, not always as well recognized, is a considerably heightened risk for childhood stroke. “Children with sickle cell disease have 100 times the risk of stroke as other children without sickle cell disease, and there’s also an elevated risk of five times the general population in adults with sickle cell disease,” said Lori Jordan, MD, PhD, in an interview.

At the 2022 annual meeting of the Child Neurology Society, Dr. Jordan spoke about stroke as a complication of sickle cell disease, and the role that neurologists can play in preventing primary or secondary strokes. “At least in children, studies have shown that if we screen and identify patients who are at highest risk of stroke, there are primary prevention therapies – usually implemented by hematologists, but that neurologists often are involved with – both monitoring for cognitive effects of silent cerebral infarct and also with treating patients who unfortunately still have an acute stroke,” said Dr. Jordan, who is an associate professor of pediatrics, neurology, and radiology at Vanderbilt University Medical Center, Nashville, Tenn. She also is director of the pediatric stroke program at Vanderbilt.
 

Time is of the essence

“In general, stroke in children is rare, but it’s more common in sickle cell disease, so it’s really important for providers to know that stroke risk is higher in those patients, particularly in those children, and then identify it and treat it earlier. Time is of the essence, and if we can give them the same therapeutics that we give the general stroke population, then time really becomes a factor, so it’s important that people know that it’s an issue for this population,” said Eboni Lance, MD, PhD, who coordinated the session where Dr. Jordan spoke.

Sickle cell disease is caused by a double mutation in the gene encoding the hemoglobin gene, producing the altered sickle hemoglobin (hemoglobin S). The change causes the hemoglobin proteins to tend to stick to one another, which can lead red blood cells to adopt a sickle-like shape. The sickle-shaped blood cells in turn have a tendency to aggregate and can block blood flow or lead to endothelial injury. Symptoms of stroke in children can include hemiparesis, aphasia, and seizure, but they can also be silent.

If no preventive is employed, one in nine with sickle cell disease will experience a stroke by the age of 19. Cerebrovascular symptoms are the most frequent debilitating complication of the condition. Nearly 40% of patients with sickle cell disease will have a silent cerebral infarct by age 18, as will 50% by age 30. Silent strokes have been associated with worse educational attainment and a greater need for educational special services.

Factors contributing to stroke in children with sickle cell disease include anemia and a low blood oxygen count, reduced oxygen affinity of hemoglobin variant, and cerebral vasculopathy. An estimated 10%-15% of young adults with sickle cell disease have severe intracranial stenosis.
 

Primary and secondary stroke prevention strategies

The dire consequences of stroke in this patient population underline the importance of primary stroke prevention, which requires the use of transcranial Doppler (TCD) ultrasound. It has been validated as a tool to screen for initial stroke risk in children with no history of stroke. High velocity measured on TCD indicates a narrowed blood vessel or elevated blood that is compensating for anemia. It adds up to a “struggling brain,” said Dr. Jordan, during her talk. If the TCD ultrasound velocity is greater than 200 cm/sec (or 170 cm/sec, depending on nonimaging versus imaging TCD), the TWiTCH trial showed that seven monthly transfusions is the number needed to treat to prevent one stroke. After 1 year, patients can be switched from transfusions to hydroxyurea if the patient has no significant intracranial stenosis. Hydroxyurea boosts both fetal and total hemoglobin, and also counters inflammation.

Following an acute stroke or transient ischemic attack, patients should receive a transfusion within 2 hours of presenting in the health care setting. American Society of Hematology guidelines recommend exchange transfusion rather than a simple transfusion. A simple transfusion can be initiated if an exchange transfusion is not available within 2 hours and hemoglobin values are less than 8.5 g/dL, to be followed by performance of exchange transfusion when available.

For chronic secondary stroke prevention, transfusions should be performed approximately monthly with the goal of maintaining hemoglobin above 9 g/dL at all times, as well as suppressing hemoglobin S levels to 30% or less of total hemoglobin.

Sudden, severe headache is a potential harbinger of complications like aneurysm, which occurs 10-fold more often among patients with sickle cell disease than the general population. It could also indicate increased intracranial pressure or cerebral venous sinus thrombosis.

Treatment of acute headache in sickle cell disease should avoid use of triptans, since vasoconstriction can counter the increased cerebral blood flow that compensates for anemia. Gabapentin and amitriptyline are good treatment choices.

New-onset seizures are a potential sign of stroke or posterior reversible leukoencephalopathy (PRES) in patients with sickle cell disease. Urgent MRI should be considered for all new-onset seizures. If blood pressure is high, PRES may be present. Seizures may also be an indicator of a previous brain injury.

Dr. Jordan has no relevant financial disclosures. Dr. Lance has served on an advisory board for Novartis.
 

CINCINNATI – Sickle cell disease is well known for its associated anemia, but patients experience a range of other complications as well. These include vision and kidney problems, delayed growth, susceptibility to infection, and pain.

Another issue, not always as well recognized, is a considerably heightened risk for childhood stroke. “Children with sickle cell disease have 100 times the risk of stroke as other children without sickle cell disease, and there’s also an elevated risk of five times the general population in adults with sickle cell disease,” said Lori Jordan, MD, PhD, in an interview.

At the 2022 annual meeting of the Child Neurology Society, Dr. Jordan spoke about stroke as a complication of sickle cell disease, and the role that neurologists can play in preventing primary or secondary strokes. “At least in children, studies have shown that if we screen and identify patients who are at highest risk of stroke, there are primary prevention therapies – usually implemented by hematologists, but that neurologists often are involved with – both monitoring for cognitive effects of silent cerebral infarct and also with treating patients who unfortunately still have an acute stroke,” said Dr. Jordan, who is an associate professor of pediatrics, neurology, and radiology at Vanderbilt University Medical Center, Nashville, Tenn. She also is director of the pediatric stroke program at Vanderbilt.
 

Time is of the essence

“In general, stroke in children is rare, but it’s more common in sickle cell disease, so it’s really important for providers to know that stroke risk is higher in those patients, particularly in those children, and then identify it and treat it earlier. Time is of the essence, and if we can give them the same therapeutics that we give the general stroke population, then time really becomes a factor, so it’s important that people know that it’s an issue for this population,” said Eboni Lance, MD, PhD, who coordinated the session where Dr. Jordan spoke.

Sickle cell disease is caused by a double mutation in the gene encoding the hemoglobin gene, producing the altered sickle hemoglobin (hemoglobin S). The change causes the hemoglobin proteins to tend to stick to one another, which can lead red blood cells to adopt a sickle-like shape. The sickle-shaped blood cells in turn have a tendency to aggregate and can block blood flow or lead to endothelial injury. Symptoms of stroke in children can include hemiparesis, aphasia, and seizure, but they can also be silent.

If no preventive is employed, one in nine with sickle cell disease will experience a stroke by the age of 19. Cerebrovascular symptoms are the most frequent debilitating complication of the condition. Nearly 40% of patients with sickle cell disease will have a silent cerebral infarct by age 18, as will 50% by age 30. Silent strokes have been associated with worse educational attainment and a greater need for educational special services.

Factors contributing to stroke in children with sickle cell disease include anemia and a low blood oxygen count, reduced oxygen affinity of hemoglobin variant, and cerebral vasculopathy. An estimated 10%-15% of young adults with sickle cell disease have severe intracranial stenosis.
 

Primary and secondary stroke prevention strategies

The dire consequences of stroke in this patient population underline the importance of primary stroke prevention, which requires the use of transcranial Doppler (TCD) ultrasound. It has been validated as a tool to screen for initial stroke risk in children with no history of stroke. High velocity measured on TCD indicates a narrowed blood vessel or elevated blood that is compensating for anemia. It adds up to a “struggling brain,” said Dr. Jordan, during her talk. If the TCD ultrasound velocity is greater than 200 cm/sec (or 170 cm/sec, depending on nonimaging versus imaging TCD), the TWiTCH trial showed that seven monthly transfusions is the number needed to treat to prevent one stroke. After 1 year, patients can be switched from transfusions to hydroxyurea if the patient has no significant intracranial stenosis. Hydroxyurea boosts both fetal and total hemoglobin, and also counters inflammation.

Following an acute stroke or transient ischemic attack, patients should receive a transfusion within 2 hours of presenting in the health care setting. American Society of Hematology guidelines recommend exchange transfusion rather than a simple transfusion. A simple transfusion can be initiated if an exchange transfusion is not available within 2 hours and hemoglobin values are less than 8.5 g/dL, to be followed by performance of exchange transfusion when available.

For chronic secondary stroke prevention, transfusions should be performed approximately monthly with the goal of maintaining hemoglobin above 9 g/dL at all times, as well as suppressing hemoglobin S levels to 30% or less of total hemoglobin.

Sudden, severe headache is a potential harbinger of complications like aneurysm, which occurs 10-fold more often among patients with sickle cell disease than the general population. It could also indicate increased intracranial pressure or cerebral venous sinus thrombosis.

Treatment of acute headache in sickle cell disease should avoid use of triptans, since vasoconstriction can counter the increased cerebral blood flow that compensates for anemia. Gabapentin and amitriptyline are good treatment choices.

New-onset seizures are a potential sign of stroke or posterior reversible leukoencephalopathy (PRES) in patients with sickle cell disease. Urgent MRI should be considered for all new-onset seizures. If blood pressure is high, PRES may be present. Seizures may also be an indicator of a previous brain injury.

Dr. Jordan has no relevant financial disclosures. Dr. Lance has served on an advisory board for Novartis.
 

In the management of acute and chronic stroke, smartphone apps enhance communication between first responders and waiting hospital staff and reduce door-to-needle time, according to a literature review.

“In clinical practice, guideline-driven patient care is very important in improving diagnosis and outcomes, and apps provide a very practical and easy way to check available guidelines,” senior author Fabio Pilato, MD, a neurologist at Università Campus Bio-Medico, Rome, told this news organization.

The review was published  in the Journal of Stroke.
 

Reviewing the literature

“My colleagues and I wanted to discover whether smartphone apps, besides just facilitating communication between doctors and their patients, could improve patient care,” said Dr. Pilato. “We wanted to see if there were any apps that could guide clinical decisions according to guidelines and whether there were some being used in acute stroke management,” he added.

The investigators reviewed 43 studies of stroke-related mobile phone apps that were designed for the clinical management of stroke between June 1, 2007, when the first iPhone was introduced, and Jan. 31, 2022.

The apps were classified into the following three groups, according to their purpose: primary prevention apps, acute stroke management apps, and postacute stroke apps.
 

Prevention and management

The investigators found one primary prevention app, the Stroke Riskometer, that was based on an algorithm derived from the Framingham Stroke Risk Score and was designed to educate patients about diet, physical activity, and the warning signs of stroke. However, their review failed to show that the app was beneficial, compared with standard cardiovascular risk reduction.

Apps appeared to aid acute stroke management, according to the researchers. Prehospital apps, such as iLAMA, Smartphone-Assisted Pre-Hospital Medical Information System, FAST-ED, Egyptian Stroke Network, Act Fast, and the Mayo Clinic Acute Stroke Evaluation app were found to speed up stroke recognition, activate emergency medical services for speedier transport to the hospital, and facilitate communication with in-hospital stroke teams. All these prehospital apps reduced door-to-needle time.

The JOIN app also was shown to significantly reduce door-to-needle time, compared with no app support, in several studies. JOIN consists of a chat, a DICOM viewer, and an encrypted two-way video system for video calls between practitioners, as well as a milestones time stamp to record every step from home to hospital transportation to therapy onset. 

StopStroke, another app that focuses on instant communication among physicians and allows real-time sharing of clinical data of stroke patients, reduced door-to-image and door-to-needle time, compared with no app.

Act Fast, which uses a National Institutes of Health Stroke Scale (NIHSS) calculator, a thrombolysis checklist, and a toolbox to share images and notes among practitioners involved in the decision-making process, decreased door-to-needle time by 16 minutes, compared with no app.

In a study of medical residents, adherence to guidelines was higher in participants who used the Mayo Clinic Acute Stroke Evaluation app, compared with those who did not. Door-to-needle time also was reduced by 16 minutes in the app-assisted group, compared with controls.
 

Postacute stroke apps

The Rehabilitation Guardian app, consisting of a health reminder, consultation, health information, and patient diary, gives medical information and provides rehabilitation exercises. Patients can enter their clinical information, and the medical staff can access it and assist with the rehab process remotely.

As for apps for chronic management and secondary prevention, Dr. Pilato and colleagues found that the PRESTRO app, which combines motivational support for a healthy lifestyle and tells patients to take their medications and measure their blood pressure, successfully got patients to be more physically active, compared with those who did not use the app.

Another app for secondary prevention, the Korea University Health Monitoring System for Stroke (KUHMS2), reduced blood pressure and glucose levels in patients who used it, compared with those who did not.

Lose It, a weight loss app, is an electronic food journal that shows the values of the macronutrients of foods that the patient consumes, as well as a daily calorie count. The Engaging Everyday Activities app effectively reminds patients who have had transient ischemic attacks about daily activities that can reduce their risk for a recurrent attack.

Movies4Stroke features educational videos about first aid, rehabilitation, how to improve swallowing, and stroke risk factors.

AFib 2gether allows patients to enter their clinical data and calculates their annual stroke risk scores. The information is provided to a health care provider before the next visit to help the patient make an informed decision about anticoagulation therapy.

“We believe that the widespread use of smartphones and apps may improve patient care in every part of the world and in particular in those parts where updated guideline consultation is not readily available. However, in our study we found that apps to implement guidelines by a clinical decision support system are still lacking. Our hope is that these apps will increase in the future,” said Dr. Pilato.
 

No panacea

Commenting on this review for this article, Amy Guzik, MD, associate professor of neurology at Wake Forest University School of Medicine, Winston-Salem, N.C., said that all physicians are looking for opportunities to use technology, especially in stroke, to diagnose and treat patients in the best way they can.

“Figuring out ways to increase efficiency and get the word out to our patients is very important to us and is probably why there are so many apps out there,” said Dr. Guzik.

“There are some ways such apps could be particularly useful. One is in remote hospitals that might not have a neurologist. Helping with the diagnosis and determining what is a bad stroke that needs to go to a higher level of medical care, or whether it is something the local hospital could take care of, would be useful,” said Dr. Guzik.

“Also helping EMS figure out which hospital to go to, or once they are on their way, being able to talk to the neurologist or neurosurgeon or the emergency room doctor and make a plan before the patient gets here, so we can expedite care when the patient arrives, is where apps can be particularly useful,” she added.

There are limitations to what apps can do, however. In the case of stroke, patients may often have important barriers that do not allow them to use apps at all, she said.

“Regardless of how they are being taken care of, a lot of our stroke patients will have problems with technology. A stroke can make texting difficult. Patients may have language difficulties, weakness, or cognitive impairment. They are relying on caregivers. All of this makes it difficult for a tech solution to be the automatic solution, unless things are done in a thoughtful way to make sure that it is appropriate for stroke patients.

“Also, there are a lot of elderly patients who may not necessarily be the most tech savvy and do not have as much digital literacy as younger patients. Another limitation to consider is that some people may not even have easy access to technology. So we must make sure that this is all done with an equity focus,” said Dr. Guzik.

The study was funded by the Associazione Nazionale fra le Imprese Assicuratrici (ANIA). Dr. Pilato and Dr. Guzik reported no relevant financial relationships.

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

In the management of acute and chronic stroke, smartphone apps enhance communication between first responders and waiting hospital staff and reduce door-to-needle time, according to a literature review.

“In clinical practice, guideline-driven patient care is very important in improving diagnosis and outcomes, and apps provide a very practical and easy way to check available guidelines,” senior author Fabio Pilato, MD, a neurologist at Università Campus Bio-Medico, Rome, told this news organization.

The review was published  in the Journal of Stroke.
 

Reviewing the literature

“My colleagues and I wanted to discover whether smartphone apps, besides just facilitating communication between doctors and their patients, could improve patient care,” said Dr. Pilato. “We wanted to see if there were any apps that could guide clinical decisions according to guidelines and whether there were some being used in acute stroke management,” he added.

The investigators reviewed 43 studies of stroke-related mobile phone apps that were designed for the clinical management of stroke between June 1, 2007, when the first iPhone was introduced, and Jan. 31, 2022.

The apps were classified into the following three groups, according to their purpose: primary prevention apps, acute stroke management apps, and postacute stroke apps.
 

Prevention and management

The investigators found one primary prevention app, the Stroke Riskometer, that was based on an algorithm derived from the Framingham Stroke Risk Score and was designed to educate patients about diet, physical activity, and the warning signs of stroke. However, their review failed to show that the app was beneficial, compared with standard cardiovascular risk reduction.

Apps appeared to aid acute stroke management, according to the researchers. Prehospital apps, such as iLAMA, Smartphone-Assisted Pre-Hospital Medical Information System, FAST-ED, Egyptian Stroke Network, Act Fast, and the Mayo Clinic Acute Stroke Evaluation app were found to speed up stroke recognition, activate emergency medical services for speedier transport to the hospital, and facilitate communication with in-hospital stroke teams. All these prehospital apps reduced door-to-needle time.

The JOIN app also was shown to significantly reduce door-to-needle time, compared with no app support, in several studies. JOIN consists of a chat, a DICOM viewer, and an encrypted two-way video system for video calls between practitioners, as well as a milestones time stamp to record every step from home to hospital transportation to therapy onset. 

StopStroke, another app that focuses on instant communication among physicians and allows real-time sharing of clinical data of stroke patients, reduced door-to-image and door-to-needle time, compared with no app.

Act Fast, which uses a National Institutes of Health Stroke Scale (NIHSS) calculator, a thrombolysis checklist, and a toolbox to share images and notes among practitioners involved in the decision-making process, decreased door-to-needle time by 16 minutes, compared with no app.

In a study of medical residents, adherence to guidelines was higher in participants who used the Mayo Clinic Acute Stroke Evaluation app, compared with those who did not. Door-to-needle time also was reduced by 16 minutes in the app-assisted group, compared with controls.
 

Postacute stroke apps

The Rehabilitation Guardian app, consisting of a health reminder, consultation, health information, and patient diary, gives medical information and provides rehabilitation exercises. Patients can enter their clinical information, and the medical staff can access it and assist with the rehab process remotely.

As for apps for chronic management and secondary prevention, Dr. Pilato and colleagues found that the PRESTRO app, which combines motivational support for a healthy lifestyle and tells patients to take their medications and measure their blood pressure, successfully got patients to be more physically active, compared with those who did not use the app.

Another app for secondary prevention, the Korea University Health Monitoring System for Stroke (KUHMS2), reduced blood pressure and glucose levels in patients who used it, compared with those who did not.

Lose It, a weight loss app, is an electronic food journal that shows the values of the macronutrients of foods that the patient consumes, as well as a daily calorie count. The Engaging Everyday Activities app effectively reminds patients who have had transient ischemic attacks about daily activities that can reduce their risk for a recurrent attack.

Movies4Stroke features educational videos about first aid, rehabilitation, how to improve swallowing, and stroke risk factors.

AFib 2gether allows patients to enter their clinical data and calculates their annual stroke risk scores. The information is provided to a health care provider before the next visit to help the patient make an informed decision about anticoagulation therapy.

“We believe that the widespread use of smartphones and apps may improve patient care in every part of the world and in particular in those parts where updated guideline consultation is not readily available. However, in our study we found that apps to implement guidelines by a clinical decision support system are still lacking. Our hope is that these apps will increase in the future,” said Dr. Pilato.
 

No panacea

Commenting on this review for this article, Amy Guzik, MD, associate professor of neurology at Wake Forest University School of Medicine, Winston-Salem, N.C., said that all physicians are looking for opportunities to use technology, especially in stroke, to diagnose and treat patients in the best way they can.

“Figuring out ways to increase efficiency and get the word out to our patients is very important to us and is probably why there are so many apps out there,” said Dr. Guzik.

“There are some ways such apps could be particularly useful. One is in remote hospitals that might not have a neurologist. Helping with the diagnosis and determining what is a bad stroke that needs to go to a higher level of medical care, or whether it is something the local hospital could take care of, would be useful,” said Dr. Guzik.

“Also helping EMS figure out which hospital to go to, or once they are on their way, being able to talk to the neurologist or neurosurgeon or the emergency room doctor and make a plan before the patient gets here, so we can expedite care when the patient arrives, is where apps can be particularly useful,” she added.

There are limitations to what apps can do, however. In the case of stroke, patients may often have important barriers that do not allow them to use apps at all, she said.

“Regardless of how they are being taken care of, a lot of our stroke patients will have problems with technology. A stroke can make texting difficult. Patients may have language difficulties, weakness, or cognitive impairment. They are relying on caregivers. All of this makes it difficult for a tech solution to be the automatic solution, unless things are done in a thoughtful way to make sure that it is appropriate for stroke patients.

“Also, there are a lot of elderly patients who may not necessarily be the most tech savvy and do not have as much digital literacy as younger patients. Another limitation to consider is that some people may not even have easy access to technology. So we must make sure that this is all done with an equity focus,” said Dr. Guzik.

The study was funded by the Associazione Nazionale fra le Imprese Assicuratrici (ANIA). Dr. Pilato and Dr. Guzik reported no relevant financial relationships.

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

In the management of acute and chronic stroke, smartphone apps enhance communication between first responders and waiting hospital staff and reduce door-to-needle time, according to a literature review.

“In clinical practice, guideline-driven patient care is very important in improving diagnosis and outcomes, and apps provide a very practical and easy way to check available guidelines,” senior author Fabio Pilato, MD, a neurologist at Università Campus Bio-Medico, Rome, told this news organization.

The review was published  in the Journal of Stroke.
 

Reviewing the literature

“My colleagues and I wanted to discover whether smartphone apps, besides just facilitating communication between doctors and their patients, could improve patient care,” said Dr. Pilato. “We wanted to see if there were any apps that could guide clinical decisions according to guidelines and whether there were some being used in acute stroke management,” he added.

The investigators reviewed 43 studies of stroke-related mobile phone apps that were designed for the clinical management of stroke between June 1, 2007, when the first iPhone was introduced, and Jan. 31, 2022.

The apps were classified into the following three groups, according to their purpose: primary prevention apps, acute stroke management apps, and postacute stroke apps.
 

Prevention and management

The investigators found one primary prevention app, the Stroke Riskometer, that was based on an algorithm derived from the Framingham Stroke Risk Score and was designed to educate patients about diet, physical activity, and the warning signs of stroke. However, their review failed to show that the app was beneficial, compared with standard cardiovascular risk reduction.

Apps appeared to aid acute stroke management, according to the researchers. Prehospital apps, such as iLAMA, Smartphone-Assisted Pre-Hospital Medical Information System, FAST-ED, Egyptian Stroke Network, Act Fast, and the Mayo Clinic Acute Stroke Evaluation app were found to speed up stroke recognition, activate emergency medical services for speedier transport to the hospital, and facilitate communication with in-hospital stroke teams. All these prehospital apps reduced door-to-needle time.

The JOIN app also was shown to significantly reduce door-to-needle time, compared with no app support, in several studies. JOIN consists of a chat, a DICOM viewer, and an encrypted two-way video system for video calls between practitioners, as well as a milestones time stamp to record every step from home to hospital transportation to therapy onset. 

StopStroke, another app that focuses on instant communication among physicians and allows real-time sharing of clinical data of stroke patients, reduced door-to-image and door-to-needle time, compared with no app.

Act Fast, which uses a National Institutes of Health Stroke Scale (NIHSS) calculator, a thrombolysis checklist, and a toolbox to share images and notes among practitioners involved in the decision-making process, decreased door-to-needle time by 16 minutes, compared with no app.

In a study of medical residents, adherence to guidelines was higher in participants who used the Mayo Clinic Acute Stroke Evaluation app, compared with those who did not. Door-to-needle time also was reduced by 16 minutes in the app-assisted group, compared with controls.
 

Postacute stroke apps

The Rehabilitation Guardian app, consisting of a health reminder, consultation, health information, and patient diary, gives medical information and provides rehabilitation exercises. Patients can enter their clinical information, and the medical staff can access it and assist with the rehab process remotely.

As for apps for chronic management and secondary prevention, Dr. Pilato and colleagues found that the PRESTRO app, which combines motivational support for a healthy lifestyle and tells patients to take their medications and measure their blood pressure, successfully got patients to be more physically active, compared with those who did not use the app.

Another app for secondary prevention, the Korea University Health Monitoring System for Stroke (KUHMS2), reduced blood pressure and glucose levels in patients who used it, compared with those who did not.

Lose It, a weight loss app, is an electronic food journal that shows the values of the macronutrients of foods that the patient consumes, as well as a daily calorie count. The Engaging Everyday Activities app effectively reminds patients who have had transient ischemic attacks about daily activities that can reduce their risk for a recurrent attack.

Movies4Stroke features educational videos about first aid, rehabilitation, how to improve swallowing, and stroke risk factors.

AFib 2gether allows patients to enter their clinical data and calculates their annual stroke risk scores. The information is provided to a health care provider before the next visit to help the patient make an informed decision about anticoagulation therapy.

“We believe that the widespread use of smartphones and apps may improve patient care in every part of the world and in particular in those parts where updated guideline consultation is not readily available. However, in our study we found that apps to implement guidelines by a clinical decision support system are still lacking. Our hope is that these apps will increase in the future,” said Dr. Pilato.
 

No panacea

Commenting on this review for this article, Amy Guzik, MD, associate professor of neurology at Wake Forest University School of Medicine, Winston-Salem, N.C., said that all physicians are looking for opportunities to use technology, especially in stroke, to diagnose and treat patients in the best way they can.

“Figuring out ways to increase efficiency and get the word out to our patients is very important to us and is probably why there are so many apps out there,” said Dr. Guzik.

“There are some ways such apps could be particularly useful. One is in remote hospitals that might not have a neurologist. Helping with the diagnosis and determining what is a bad stroke that needs to go to a higher level of medical care, or whether it is something the local hospital could take care of, would be useful,” said Dr. Guzik.

“Also helping EMS figure out which hospital to go to, or once they are on their way, being able to talk to the neurologist or neurosurgeon or the emergency room doctor and make a plan before the patient gets here, so we can expedite care when the patient arrives, is where apps can be particularly useful,” she added.

There are limitations to what apps can do, however. In the case of stroke, patients may often have important barriers that do not allow them to use apps at all, she said.

“Regardless of how they are being taken care of, a lot of our stroke patients will have problems with technology. A stroke can make texting difficult. Patients may have language difficulties, weakness, or cognitive impairment. They are relying on caregivers. All of this makes it difficult for a tech solution to be the automatic solution, unless things are done in a thoughtful way to make sure that it is appropriate for stroke patients.

“Also, there are a lot of elderly patients who may not necessarily be the most tech savvy and do not have as much digital literacy as younger patients. Another limitation to consider is that some people may not even have easy access to technology. So we must make sure that this is all done with an equity focus,” said Dr. Guzik.

The study was funded by the Associazione Nazionale fra le Imprese Assicuratrici (ANIA). Dr. Pilato and Dr. Guzik reported no relevant financial relationships.

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

The authors of a new evidence review recommend the Canadian TIA Risk Score for managing patients who present to the emergency department or physician’s office with an apparent transient ischemic attack (TIA) or minor stroke.

“Many hospitals do not have enough stroke neurologists to see every patient with TIA or minor stroke within 24 hours. Likewise, many emergency departments around the world are stretched beyond capacity,” study author Jeffery J. Perry, MD, senior scientist at the Ottawa Hospital Research Institute, said in an interview.

“This review corresponds to most of the recommendations by the American Heart Association and the Canadian Stroke Best Practice Recommendations,” he said. “It does, however, go further to differentiate high-risk versus low-risk patients for subsequent stroke using the Canadian TIA Score and offers practical suggestions for how to provide high-quality care in environments without the capacity to provide immediate vascular imaging, immediate MRI scanning, and immediate stroke specialist assessments.”

Most patients at low risk of a subsequent stroke (that is, patients with < 1% risk for a subsequent stroke at 7 days) can be managed safely as outpatients without causing delays in their departure for vascular imaging or neurology consultation during their initial emergency department visits, Dr. Perry added. “The Canadian TIA Score can be used to determine the urgency for an assessment by a stroke neurologist.”

The study was published  in CMAJ.
 

Score stratifies risk

Dr. Perry, lead author of the Canadian TIA Score validation study, said that the CMAJ editorial board approached him to write the review and to incorporate the new score into the latest recommendations. To include the latest evidence, Dr. Perry and colleagues reviewed the most recent position statements on TIA and minor stroke management and searched the literature for relevant articles. They note that the nomenclature related to TIA and minor stroke is inconsistent, that it’s not necessary to differentiate between the two from a clinical standpoint, and that the term “acute ischemic cerebrovascular syndrome” has been proposed to include both.

Broadly, the team’s recommended strategy for the diagnosis and management of the condition includes the following steps:

• Diagnosis: Sudden loss of motor function and impaired speech are strong indicators; symptoms tend to be negative (for example, loss of vision rather than flashing lights).
• Risk assessment: Use of the Canadian TIA Score to stratify 7-day stroke risk (low risk: < 1%, medium risk: 1%-5%, high risk: > 5%).
• Investigations: Urgent CT within 48 hours; vascular imaging to identify acutely symptomatic carotid stenosis in medium- to high-risk patients, as determined on the basis of the TIA score; ECG to identify atrial fibrillation or flutter and to optimize anticoagulant use; if the index of suspicion is high, echocardiography should be employed to look for cardioembolic sources.
• Management: Dual antiplatelet therapy for 21 days in medium- and high-risk patients; hypertension should be managed; patients should be referred for stroke clinic assessment; aggressive lifestyle changes should be initiated to lower lipid levels.

“I believe that our recommendations should be incorporated with the clinical guidelines,” said Dr. Perry.
 

Caveats and concerns

Commenting on the article, Steven M. Greenberg, MD, PhD, vice chair for faculty development of the department of neurology at Massachusetts General Hospital and a professor of neurology at Harvard Medical School, both in Boston, said, “Although the proposed guidelines are broadly evidence-based and consistent with standard of care, there are several areas where stroke specialists might disagree and suggest alternative strategies.” Dr. Greenberg was not involved in the study.

While some lower-risk features, such as repetitive or stereotyped symptoms or vertigo, can be more suggestive of TIA mimics, he said that “these features need to be scrutinized quite carefully. Critical carotid stenosis, for example, can give rise to brief, repetitive, stereotyped low-flow TIAs that require urgent revascularization.”

Vertigo might be a feature of brainstem or cerebellar TIA or minor stroke, said Dr. Greenberg, especially in the setting of other posterior circulation symptoms. Validated guidelines for differentiating peripheral vertigo and CNS vertigo are available, he noted.

“Another caveat is that the studies demonstrating benefit of brief dual antiplatelet therapy following acute TIA or minor stroke were based on ABCD2 rather than the Canadian TIA score,” he said. “It is therefore important for any score-based recommendations to be applied in the overall context of existing stroke prevention guidelines.”

In addition to the recommendation for urgent vascular imaging of patients whose presentations suggest bona fide TIA or minor stroke, most guidelines also recommend extended cardiac monitoring and transthoracic ECG to identify potential sources of embolism, Dr. Greenberg added. “Users of these guidelines should also be aware of the limited yield of head CT, which is able to detect some old strokes, large acute strokes – presumably not relevant to patients presenting with TIA or minor stroke – and acute intracranial hemorrhages.”

Louis R. Caplan, MD, founder of the Harvard Stroke Registry at Beth Israel Deaconess Medical Center, Boston, and a professor of neurology at Harvard Medical School, also commented on the study.

While the review “is okay for care by nonstroke specialists, ideally, major referral centers could have a TIA or stroke clinic, as is present in much of Western Europe,” he said. This would allow the stroke etiology to be investigated for each patient.

“Many patients can be treated with the regimen outlined by the authors, but some with other conditions, such as atrial cardiopathy, patent foramen ovale, atrial myxoma, thrombus within the cardiac ventricle or atrium, will require anticoagulants,” he noted. “Thrombolysis and mechanical thrombectomy would be considered in some. Each stroke patient is different, and management cannot be homogenized into one remedy. One size does not fit all.”

In an accompanying commentary, Shelagh B. Coutts, MD, and Michael D. Hill, MD, both of the University of Calgary (Alta.), presented their team’s approach to the acute management of patients with likely cerebral ischemia. Such management includes risk assessment and stratification by clinical symptoms, rather than a particular score. They also typically conduct CT angiography. “If the CTA is completely normal (that is, no occlusion, no atherosclerosis or arterial dissection and no other vascular abnormality), we rely on the high negative predictive value of this result and discharge the patient home on antiplatelet treatment with outpatient follow-up, including MRI of the brain (since CT cannot reliably rule out minor ischemia) within the first week,” they write.

The review was conducted without commercial funding. Dr. Perry, Dr. Greenberg, Dr. Caplan, Dr. Coutts, and Dr. Hill have disclosed no relevant financial relationships.

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

The authors of a new evidence review recommend the Canadian TIA Risk Score for managing patients who present to the emergency department or physician’s office with an apparent transient ischemic attack (TIA) or minor stroke.

“Many hospitals do not have enough stroke neurologists to see every patient with TIA or minor stroke within 24 hours. Likewise, many emergency departments around the world are stretched beyond capacity,” study author Jeffery J. Perry, MD, senior scientist at the Ottawa Hospital Research Institute, said in an interview.

“This review corresponds to most of the recommendations by the American Heart Association and the Canadian Stroke Best Practice Recommendations,” he said. “It does, however, go further to differentiate high-risk versus low-risk patients for subsequent stroke using the Canadian TIA Score and offers practical suggestions for how to provide high-quality care in environments without the capacity to provide immediate vascular imaging, immediate MRI scanning, and immediate stroke specialist assessments.”

Most patients at low risk of a subsequent stroke (that is, patients with < 1% risk for a subsequent stroke at 7 days) can be managed safely as outpatients without causing delays in their departure for vascular imaging or neurology consultation during their initial emergency department visits, Dr. Perry added. “The Canadian TIA Score can be used to determine the urgency for an assessment by a stroke neurologist.”

The study was published  in CMAJ.
 

Score stratifies risk

Dr. Perry, lead author of the Canadian TIA Score validation study, said that the CMAJ editorial board approached him to write the review and to incorporate the new score into the latest recommendations. To include the latest evidence, Dr. Perry and colleagues reviewed the most recent position statements on TIA and minor stroke management and searched the literature for relevant articles. They note that the nomenclature related to TIA and minor stroke is inconsistent, that it’s not necessary to differentiate between the two from a clinical standpoint, and that the term “acute ischemic cerebrovascular syndrome” has been proposed to include both.

Broadly, the team’s recommended strategy for the diagnosis and management of the condition includes the following steps:

• Diagnosis: Sudden loss of motor function and impaired speech are strong indicators; symptoms tend to be negative (for example, loss of vision rather than flashing lights).
• Risk assessment: Use of the Canadian TIA Score to stratify 7-day stroke risk (low risk: < 1%, medium risk: 1%-5%, high risk: > 5%).
• Investigations: Urgent CT within 48 hours; vascular imaging to identify acutely symptomatic carotid stenosis in medium- to high-risk patients, as determined on the basis of the TIA score; ECG to identify atrial fibrillation or flutter and to optimize anticoagulant use; if the index of suspicion is high, echocardiography should be employed to look for cardioembolic sources.
• Management: Dual antiplatelet therapy for 21 days in medium- and high-risk patients; hypertension should be managed; patients should be referred for stroke clinic assessment; aggressive lifestyle changes should be initiated to lower lipid levels.

“I believe that our recommendations should be incorporated with the clinical guidelines,” said Dr. Perry.
 

Caveats and concerns

Commenting on the article, Steven M. Greenberg, MD, PhD, vice chair for faculty development of the department of neurology at Massachusetts General Hospital and a professor of neurology at Harvard Medical School, both in Boston, said, “Although the proposed guidelines are broadly evidence-based and consistent with standard of care, there are several areas where stroke specialists might disagree and suggest alternative strategies.” Dr. Greenberg was not involved in the study.

While some lower-risk features, such as repetitive or stereotyped symptoms or vertigo, can be more suggestive of TIA mimics, he said that “these features need to be scrutinized quite carefully. Critical carotid stenosis, for example, can give rise to brief, repetitive, stereotyped low-flow TIAs that require urgent revascularization.”

Vertigo might be a feature of brainstem or cerebellar TIA or minor stroke, said Dr. Greenberg, especially in the setting of other posterior circulation symptoms. Validated guidelines for differentiating peripheral vertigo and CNS vertigo are available, he noted.

“Another caveat is that the studies demonstrating benefit of brief dual antiplatelet therapy following acute TIA or minor stroke were based on ABCD2 rather than the Canadian TIA score,” he said. “It is therefore important for any score-based recommendations to be applied in the overall context of existing stroke prevention guidelines.”

In addition to the recommendation for urgent vascular imaging of patients whose presentations suggest bona fide TIA or minor stroke, most guidelines also recommend extended cardiac monitoring and transthoracic ECG to identify potential sources of embolism, Dr. Greenberg added. “Users of these guidelines should also be aware of the limited yield of head CT, which is able to detect some old strokes, large acute strokes – presumably not relevant to patients presenting with TIA or minor stroke – and acute intracranial hemorrhages.”

Louis R. Caplan, MD, founder of the Harvard Stroke Registry at Beth Israel Deaconess Medical Center, Boston, and a professor of neurology at Harvard Medical School, also commented on the study.

While the review “is okay for care by nonstroke specialists, ideally, major referral centers could have a TIA or stroke clinic, as is present in much of Western Europe,” he said. This would allow the stroke etiology to be investigated for each patient.

“Many patients can be treated with the regimen outlined by the authors, but some with other conditions, such as atrial cardiopathy, patent foramen ovale, atrial myxoma, thrombus within the cardiac ventricle or atrium, will require anticoagulants,” he noted. “Thrombolysis and mechanical thrombectomy would be considered in some. Each stroke patient is different, and management cannot be homogenized into one remedy. One size does not fit all.”

In an accompanying commentary, Shelagh B. Coutts, MD, and Michael D. Hill, MD, both of the University of Calgary (Alta.), presented their team’s approach to the acute management of patients with likely cerebral ischemia. Such management includes risk assessment and stratification by clinical symptoms, rather than a particular score. They also typically conduct CT angiography. “If the CTA is completely normal (that is, no occlusion, no atherosclerosis or arterial dissection and no other vascular abnormality), we rely on the high negative predictive value of this result and discharge the patient home on antiplatelet treatment with outpatient follow-up, including MRI of the brain (since CT cannot reliably rule out minor ischemia) within the first week,” they write.

The review was conducted without commercial funding. Dr. Perry, Dr. Greenberg, Dr. Caplan, Dr. Coutts, and Dr. Hill have disclosed no relevant financial relationships.

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

The authors of a new evidence review recommend the Canadian TIA Risk Score for managing patients who present to the emergency department or physician’s office with an apparent transient ischemic attack (TIA) or minor stroke.

“Many hospitals do not have enough stroke neurologists to see every patient with TIA or minor stroke within 24 hours. Likewise, many emergency departments around the world are stretched beyond capacity,” study author Jeffery J. Perry, MD, senior scientist at the Ottawa Hospital Research Institute, said in an interview.

“This review corresponds to most of the recommendations by the American Heart Association and the Canadian Stroke Best Practice Recommendations,” he said. “It does, however, go further to differentiate high-risk versus low-risk patients for subsequent stroke using the Canadian TIA Score and offers practical suggestions for how to provide high-quality care in environments without the capacity to provide immediate vascular imaging, immediate MRI scanning, and immediate stroke specialist assessments.”

Most patients at low risk of a subsequent stroke (that is, patients with < 1% risk for a subsequent stroke at 7 days) can be managed safely as outpatients without causing delays in their departure for vascular imaging or neurology consultation during their initial emergency department visits, Dr. Perry added. “The Canadian TIA Score can be used to determine the urgency for an assessment by a stroke neurologist.”

The study was published  in CMAJ.
 

Score stratifies risk

Dr. Perry, lead author of the Canadian TIA Score validation study, said that the CMAJ editorial board approached him to write the review and to incorporate the new score into the latest recommendations. To include the latest evidence, Dr. Perry and colleagues reviewed the most recent position statements on TIA and minor stroke management and searched the literature for relevant articles. They note that the nomenclature related to TIA and minor stroke is inconsistent, that it’s not necessary to differentiate between the two from a clinical standpoint, and that the term “acute ischemic cerebrovascular syndrome” has been proposed to include both.

Broadly, the team’s recommended strategy for the diagnosis and management of the condition includes the following steps:

• Diagnosis: Sudden loss of motor function and impaired speech are strong indicators; symptoms tend to be negative (for example, loss of vision rather than flashing lights).
• Risk assessment: Use of the Canadian TIA Score to stratify 7-day stroke risk (low risk: < 1%, medium risk: 1%-5%, high risk: > 5%).
• Investigations: Urgent CT within 48 hours; vascular imaging to identify acutely symptomatic carotid stenosis in medium- to high-risk patients, as determined on the basis of the TIA score; ECG to identify atrial fibrillation or flutter and to optimize anticoagulant use; if the index of suspicion is high, echocardiography should be employed to look for cardioembolic sources.
• Management: Dual antiplatelet therapy for 21 days in medium- and high-risk patients; hypertension should be managed; patients should be referred for stroke clinic assessment; aggressive lifestyle changes should be initiated to lower lipid levels.

“I believe that our recommendations should be incorporated with the clinical guidelines,” said Dr. Perry.
 

Caveats and concerns

Commenting on the article, Steven M. Greenberg, MD, PhD, vice chair for faculty development of the department of neurology at Massachusetts General Hospital and a professor of neurology at Harvard Medical School, both in Boston, said, “Although the proposed guidelines are broadly evidence-based and consistent with standard of care, there are several areas where stroke specialists might disagree and suggest alternative strategies.” Dr. Greenberg was not involved in the study.

While some lower-risk features, such as repetitive or stereotyped symptoms or vertigo, can be more suggestive of TIA mimics, he said that “these features need to be scrutinized quite carefully. Critical carotid stenosis, for example, can give rise to brief, repetitive, stereotyped low-flow TIAs that require urgent revascularization.”

Vertigo might be a feature of brainstem or cerebellar TIA or minor stroke, said Dr. Greenberg, especially in the setting of other posterior circulation symptoms. Validated guidelines for differentiating peripheral vertigo and CNS vertigo are available, he noted.

“Another caveat is that the studies demonstrating benefit of brief dual antiplatelet therapy following acute TIA or minor stroke were based on ABCD2 rather than the Canadian TIA score,” he said. “It is therefore important for any score-based recommendations to be applied in the overall context of existing stroke prevention guidelines.”

In addition to the recommendation for urgent vascular imaging of patients whose presentations suggest bona fide TIA or minor stroke, most guidelines also recommend extended cardiac monitoring and transthoracic ECG to identify potential sources of embolism, Dr. Greenberg added. “Users of these guidelines should also be aware of the limited yield of head CT, which is able to detect some old strokes, large acute strokes – presumably not relevant to patients presenting with TIA or minor stroke – and acute intracranial hemorrhages.”

Louis R. Caplan, MD, founder of the Harvard Stroke Registry at Beth Israel Deaconess Medical Center, Boston, and a professor of neurology at Harvard Medical School, also commented on the study.

While the review “is okay for care by nonstroke specialists, ideally, major referral centers could have a TIA or stroke clinic, as is present in much of Western Europe,” he said. This would allow the stroke etiology to be investigated for each patient.

“Many patients can be treated with the regimen outlined by the authors, but some with other conditions, such as atrial cardiopathy, patent foramen ovale, atrial myxoma, thrombus within the cardiac ventricle or atrium, will require anticoagulants,” he noted. “Thrombolysis and mechanical thrombectomy would be considered in some. Each stroke patient is different, and management cannot be homogenized into one remedy. One size does not fit all.”

In an accompanying commentary, Shelagh B. Coutts, MD, and Michael D. Hill, MD, both of the University of Calgary (Alta.), presented their team’s approach to the acute management of patients with likely cerebral ischemia. Such management includes risk assessment and stratification by clinical symptoms, rather than a particular score. They also typically conduct CT angiography. “If the CTA is completely normal (that is, no occlusion, no atherosclerosis or arterial dissection and no other vascular abnormality), we rely on the high negative predictive value of this result and discharge the patient home on antiplatelet treatment with outpatient follow-up, including MRI of the brain (since CT cannot reliably rule out minor ischemia) within the first week,” they write.

The review was conducted without commercial funding. Dr. Perry, Dr. Greenberg, Dr. Caplan, Dr. Coutts, and Dr. Hill have disclosed no relevant financial relationships.

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

Diabetes persists as a risk factor for cardiovascular events, but where it once meant the same risk of heart attack or stroke as cardiovascular disease itself, a large Canadian population study reports that’s no longer the case. Thanks to advances in diabetes management over the past quarter century, diabetes is no longer considered equivalent to CVD as a risk factor for cardiovascular events, researchers from the University of Toronto reported.

The retrospective, population-based study used administrative data from Ontario’s provincial universal health care system. The researchers created five population-based cohorts of adults at 5-year intervals from 1994 to 2014, consisting of 1.87 million adults in the first cohort and 1.5 million in the last. In that 20-year span, the prevalence of diabetes in this population tripled, from 3.1% to 9%.

“In the last 25 years we’ve seen wholesale changes in the way people approach diabetes,” lead study author Calvin Ke, MD, PhD, an endocrinologist and assistant professor at the University of Toronto, said in an interview. “Part of the findings show that diabetes and cardiovascular disease were equivalent for risk of cardiovascular events in 1994, but by 2014 that was not the case.”

However, Dr. Ke added, “Diabetes is still a very strong cardiovascular risk factor.”

The investigators for the study, reported as a research letter in JAMA, analyzed the risk of cardiovascular events in four subgroups: those who had both diabetes and CVD, CVD only, diabetes only, and no CVD or diabetes.

Between 1994 and 2014, the cardiovascular event rates declined significantly among people with diabetes alone, compared with people with no disease: from 28.4 to 12.7 per 1,000 person-years, or an absolute risk increase (ARI) of 4.4% and a relative risk (RR) more than double (2.06), in 1994 to 14 vs. 8 per 1,000 person-years, and an ARI of 2% and RR less than double (1.58) 20 years later.

Among people with CVD only, those values shifted from 36.1 per 1,000 person-years, ARI of 5.1% and RR of 2.16 in 1994 to 23.9, ARI of 3.7% and RR still more than double (2.06) in 2014.

People with both CVD and diabetes had the highest CVD event rates across all 5-year cohorts: 74 per 1,000 person-years, ARI of 12% and RR almost four times greater (3.81) in 1994 than people with no disease. By 2014, the ARI in this group was 7.6% and the RR 3.10.

The investigators calculated that event rates from 1994 to 2014 declined across all four subgroups, with rate ratios of 0.49 for diabetes only, 0.66 for CVD only, 0.60 for both diabetes and CVD, and 0.63 for neither disease.

Shift in practice

The study noted that the shift in diabetes as a risk factor for heart attack and stroke is “a change that likely reflects the use of modern, multifactorial approaches to diabetes.”

“A number of changes have occurred in practice that really focus on this idea of a multifactorial approach to diabetes: more aggressive management of blood sugar, blood pressure, and lipids,” Dr. Ke said. “We know from the statin trials that statins can reduce the risk of heart disease significantly, and the use of statins increased from 28.4% in 1999 to 56.3% in 2018 in the United States,” Dr. Ke said. He added that statin use in Canada in adults ages 40 and older went from 1.2% in 1994 to 58.4% in 2010-2015. Use of ACE inhibitors and angiotensin receptor blockers for hypertension followed similar trends, contributing further to reducing risks for heart attack and stroke, Dr. Ke said.

Dr. Ke also noted that the evolution of guidelines and advances in treatments for both CVD and diabetes since 1994 have contributed to improving risks for people with diabetes. SGLT2 inhibitors have been linked to a 2%-6% reduction in hemoglobin A1c, he said. “All of these factors combined have had a major effect on the reduced risk of cardiovascular events.”

Prakash Deedwania, MD, professor at the University of California, San Francisco, Fresno, said that this study confirms a trend that others have reported regarding the risk of CVD in diabetes. The large database covering millions of adults is a study strength, he said.

And the findings, Dr. Deedwania added, underscore what’s been published in clinical guidelines, notably the American Heart Association scientific statement for managing CVD risk in patients with diabetes. “This means that, from observations made 20-plus years ago, when most people were not being treated for diabetes or heart disease, the pendulum has swung,” he said.

However, he added, “The authors state clearly that it does not mean that diabetes is not associated with a higher risk of cardiovascular events; it just means it is no longer equivalent to CVD.”

Managing diabetes continues to be “particularly important,” Dr. Deedwania said, because the prevalence of diabetes continues to rise. “This is a phenomenal risk, and it emphasizes that, to really conquer or control diabetes, we should make every effort to prevent diabetes,” he said.

Dr. Ke and Dr. Deedwania have no relevant financial relationships to disclose.

Diabetes persists as a risk factor for cardiovascular events, but where it once meant the same risk of heart attack or stroke as cardiovascular disease itself, a large Canadian population study reports that’s no longer the case. Thanks to advances in diabetes management over the past quarter century, diabetes is no longer considered equivalent to CVD as a risk factor for cardiovascular events, researchers from the University of Toronto reported.

The retrospective, population-based study used administrative data from Ontario’s provincial universal health care system. The researchers created five population-based cohorts of adults at 5-year intervals from 1994 to 2014, consisting of 1.87 million adults in the first cohort and 1.5 million in the last. In that 20-year span, the prevalence of diabetes in this population tripled, from 3.1% to 9%.

“In the last 25 years we’ve seen wholesale changes in the way people approach diabetes,” lead study author Calvin Ke, MD, PhD, an endocrinologist and assistant professor at the University of Toronto, said in an interview. “Part of the findings show that diabetes and cardiovascular disease were equivalent for risk of cardiovascular events in 1994, but by 2014 that was not the case.”

However, Dr. Ke added, “Diabetes is still a very strong cardiovascular risk factor.”

The investigators for the study, reported as a research letter in JAMA, analyzed the risk of cardiovascular events in four subgroups: those who had both diabetes and CVD, CVD only, diabetes only, and no CVD or diabetes.

Between 1994 and 2014, the cardiovascular event rates declined significantly among people with diabetes alone, compared with people with no disease: from 28.4 to 12.7 per 1,000 person-years, or an absolute risk increase (ARI) of 4.4% and a relative risk (RR) more than double (2.06), in 1994 to 14 vs. 8 per 1,000 person-years, and an ARI of 2% and RR less than double (1.58) 20 years later.

Among people with CVD only, those values shifted from 36.1 per 1,000 person-years, ARI of 5.1% and RR of 2.16 in 1994 to 23.9, ARI of 3.7% and RR still more than double (2.06) in 2014.

People with both CVD and diabetes had the highest CVD event rates across all 5-year cohorts: 74 per 1,000 person-years, ARI of 12% and RR almost four times greater (3.81) in 1994 than people with no disease. By 2014, the ARI in this group was 7.6% and the RR 3.10.

The investigators calculated that event rates from 1994 to 2014 declined across all four subgroups, with rate ratios of 0.49 for diabetes only, 0.66 for CVD only, 0.60 for both diabetes and CVD, and 0.63 for neither disease.

Shift in practice

The study noted that the shift in diabetes as a risk factor for heart attack and stroke is “a change that likely reflects the use of modern, multifactorial approaches to diabetes.”

“A number of changes have occurred in practice that really focus on this idea of a multifactorial approach to diabetes: more aggressive management of blood sugar, blood pressure, and lipids,” Dr. Ke said. “We know from the statin trials that statins can reduce the risk of heart disease significantly, and the use of statins increased from 28.4% in 1999 to 56.3% in 2018 in the United States,” Dr. Ke said. He added that statin use in Canada in adults ages 40 and older went from 1.2% in 1994 to 58.4% in 2010-2015. Use of ACE inhibitors and angiotensin receptor blockers for hypertension followed similar trends, contributing further to reducing risks for heart attack and stroke, Dr. Ke said.

Dr. Ke also noted that the evolution of guidelines and advances in treatments for both CVD and diabetes since 1994 have contributed to improving risks for people with diabetes. SGLT2 inhibitors have been linked to a 2%-6% reduction in hemoglobin A1c, he said. “All of these factors combined have had a major effect on the reduced risk of cardiovascular events.”

Prakash Deedwania, MD, professor at the University of California, San Francisco, Fresno, said that this study confirms a trend that others have reported regarding the risk of CVD in diabetes. The large database covering millions of adults is a study strength, he said.

And the findings, Dr. Deedwania added, underscore what’s been published in clinical guidelines, notably the American Heart Association scientific statement for managing CVD risk in patients with diabetes. “This means that, from observations made 20-plus years ago, when most people were not being treated for diabetes or heart disease, the pendulum has swung,” he said.

However, he added, “The authors state clearly that it does not mean that diabetes is not associated with a higher risk of cardiovascular events; it just means it is no longer equivalent to CVD.”

Managing diabetes continues to be “particularly important,” Dr. Deedwania said, because the prevalence of diabetes continues to rise. “This is a phenomenal risk, and it emphasizes that, to really conquer or control diabetes, we should make every effort to prevent diabetes,” he said.

Dr. Ke and Dr. Deedwania have no relevant financial relationships to disclose.

Diabetes persists as a risk factor for cardiovascular events, but where it once meant the same risk of heart attack or stroke as cardiovascular disease itself, a large Canadian population study reports that’s no longer the case. Thanks to advances in diabetes management over the past quarter century, diabetes is no longer considered equivalent to CVD as a risk factor for cardiovascular events, researchers from the University of Toronto reported.

The retrospective, population-based study used administrative data from Ontario’s provincial universal health care system. The researchers created five population-based cohorts of adults at 5-year intervals from 1994 to 2014, consisting of 1.87 million adults in the first cohort and 1.5 million in the last. In that 20-year span, the prevalence of diabetes in this population tripled, from 3.1% to 9%.

“In the last 25 years we’ve seen wholesale changes in the way people approach diabetes,” lead study author Calvin Ke, MD, PhD, an endocrinologist and assistant professor at the University of Toronto, said in an interview. “Part of the findings show that diabetes and cardiovascular disease were equivalent for risk of cardiovascular events in 1994, but by 2014 that was not the case.”

However, Dr. Ke added, “Diabetes is still a very strong cardiovascular risk factor.”

The investigators for the study, reported as a research letter in JAMA, analyzed the risk of cardiovascular events in four subgroups: those who had both diabetes and CVD, CVD only, diabetes only, and no CVD or diabetes.

Between 1994 and 2014, the cardiovascular event rates declined significantly among people with diabetes alone, compared with people with no disease: from 28.4 to 12.7 per 1,000 person-years, or an absolute risk increase (ARI) of 4.4% and a relative risk (RR) more than double (2.06), in 1994 to 14 vs. 8 per 1,000 person-years, and an ARI of 2% and RR less than double (1.58) 20 years later.

Among people with CVD only, those values shifted from 36.1 per 1,000 person-years, ARI of 5.1% and RR of 2.16 in 1994 to 23.9, ARI of 3.7% and RR still more than double (2.06) in 2014.

People with both CVD and diabetes had the highest CVD event rates across all 5-year cohorts: 74 per 1,000 person-years, ARI of 12% and RR almost four times greater (3.81) in 1994 than people with no disease. By 2014, the ARI in this group was 7.6% and the RR 3.10.

The investigators calculated that event rates from 1994 to 2014 declined across all four subgroups, with rate ratios of 0.49 for diabetes only, 0.66 for CVD only, 0.60 for both diabetes and CVD, and 0.63 for neither disease.

Shift in practice

The study noted that the shift in diabetes as a risk factor for heart attack and stroke is “a change that likely reflects the use of modern, multifactorial approaches to diabetes.”

“A number of changes have occurred in practice that really focus on this idea of a multifactorial approach to diabetes: more aggressive management of blood sugar, blood pressure, and lipids,” Dr. Ke said. “We know from the statin trials that statins can reduce the risk of heart disease significantly, and the use of statins increased from 28.4% in 1999 to 56.3% in 2018 in the United States,” Dr. Ke said. He added that statin use in Canada in adults ages 40 and older went from 1.2% in 1994 to 58.4% in 2010-2015. Use of ACE inhibitors and angiotensin receptor blockers for hypertension followed similar trends, contributing further to reducing risks for heart attack and stroke, Dr. Ke said.

Dr. Ke also noted that the evolution of guidelines and advances in treatments for both CVD and diabetes since 1994 have contributed to improving risks for people with diabetes. SGLT2 inhibitors have been linked to a 2%-6% reduction in hemoglobin A1c, he said. “All of these factors combined have had a major effect on the reduced risk of cardiovascular events.”

Prakash Deedwania, MD, professor at the University of California, San Francisco, Fresno, said that this study confirms a trend that others have reported regarding the risk of CVD in diabetes. The large database covering millions of adults is a study strength, he said.

And the findings, Dr. Deedwania added, underscore what’s been published in clinical guidelines, notably the American Heart Association scientific statement for managing CVD risk in patients with diabetes. “This means that, from observations made 20-plus years ago, when most people were not being treated for diabetes or heart disease, the pendulum has swung,” he said.

However, he added, “The authors state clearly that it does not mean that diabetes is not associated with a higher risk of cardiovascular events; it just means it is no longer equivalent to CVD.”

Managing diabetes continues to be “particularly important,” Dr. Deedwania said, because the prevalence of diabetes continues to rise. “This is a phenomenal risk, and it emphasizes that, to really conquer or control diabetes, we should make every effort to prevent diabetes,” he said.

Dr. Ke and Dr. Deedwania have no relevant financial relationships to disclose.

Apixaban offers greater protection than rivaroxaban against ischemic stroke, systemic embolism, and bleeding in patients with both atrial fibrillation (AFib) and valvular heart disease (VHD), a new study finds.

Compared with rivaroxaban, apixaban cut risks nearly in half, suggesting that clinicians should consider these new data when choosing an anticoagulant, reported lead author Ghadeer K. Dawwas, PhD, of the University of Pennsylvania, Philadelphia, and colleagues.

In the new retrospective study involving almost 20,000 patients, Dr. Dawwas and her colleagues “emulated a target trial” using private insurance claims from Optum’s deidentified Clinformatics Data Mart Database. The cohort was narrowed from a screened population of 58,210 patients with concurrent AFib and VHD to 9,947 new apixaban users who could be closely matched with 9,947 new rivaroxaban users. Covariates included provider specialty, type of VHD, demographic characteristics, measures of health care use, baseline use of medications, and baseline comorbidities.

The primary effectiveness outcome was a composite of systemic embolism and ischemic stroke, while the primary safety outcome was a composite of intracranial or gastrointestinal bleeding.

“Although several ongoing trials aim to compare apixaban with warfarin in patients with AFib and VHD, none of these trials will directly compare apixaban and rivaroxaban,” the investigators wrote. Their report is in Annals of Internal Medicine.

Dr. Dawwas and colleagues previously showed that direct oral anticoagulants (DOACs) were safer and more effective than warfarin in the same patient population. Comparing apixaban and rivaroxaban – the two most common DOACs – was the next logical step, Dr. Dawwas said in an interview.
 

Study results

Compared with rivaroxaban, patients who received apixaban had a 43% reduced risk of stroke or embolism (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.40-0.80). Apixaban’s ability to protect against bleeding appeared even more pronounced, with a 49% reduced risk over rivaroxaban (HR, 0.51; 95% CI, 0.41-0.62).

Comparing the two agents on an absolute basis, apixaban reduced risk of embolism or stroke by 0.2% within the first 6 months of treatment initiation, and 1.1% within the first year of initiation. At the same time points, absolute risk reductions for bleeding were 1.2% and 1.9%, respectively.

The investigators noted that their results held consistent in an alternative analysis that considered separate types of VHD.

“Based on the results from our analysis, we showed that apixaban is effective and safe in patients with atrial fibrillation and valvular heart diseases,” Dr. Dawwas said.
 

Head-to-head trial needed to change practice

Christopher M. Bianco, DO, associate professor of medicine at West Virginia University Heart and Vascular Institute, Morgantown, said the findings “add to the growing body of literature,” but “a head-to-head trial would be necessary to make a definitive change to clinical practice.”

Dr. Bianco, who recently conducted a retrospective analysis of apixaban and rivaroxaban that found no difference in safety and efficacy among a different patient population, said these kinds of studies are helpful in generating hypotheses, but they can’t account for all relevant clinical factors.

“There are just so many things that go into the decision-making process of [prescribing] apixaban and rivaroxaban,” he said. “Even though [Dr. Dawwas and colleagues] used propensity matching, you’re never going to be able to sort that out with a retrospective analysis.”

Specifically, Dr. Bianco noted that the findings did not include dose data. This is a key gap, he said, considering how often real-world datasets have shown that providers underdose DOACs for a number of unaccountable reasons, and how frequently patients exhibit poor adherence.

The study also lacked detail concerning the degree of renal dysfunction, which can determine drug eligibility, Dr. Bianco said. Furthermore, attempts to stratify patients based on thrombosis and bleeding risk were likely “insufficient,” he added.

Dr. Bianco also cautioned that the investigators defined valvular heart disease as any valve-related disease of any severity. In contrast, previous studies have generally restricted valvular heart disease to patients with mitral stenosis or prosthetic valves.

“This is definitely not the traditional definition of valvular heart disease, so the title is a little bit misleading in that sense, although they certainly do disclose that in the methods,” Dr. Bianco said.

On a more positive note, he highlighted the size of the patient population, and the real-world data, which included many patients who would be excluded from clinical trials.

More broadly, the study helps drive research forward, Dr. Bianco concluded; namely, by attracting financial support for a more powerful head-to-head trial that drug makers are unlikely to fund due to inherent market risk.

This study was supported by the National Institutes of Health. The investigators disclosed additional relationships with Takeda, Spark, Sanofi, and others. Dr. Bianco disclosed no conflicts of interest.

Apixaban offers greater protection than rivaroxaban against ischemic stroke, systemic embolism, and bleeding in patients with both atrial fibrillation (AFib) and valvular heart disease (VHD), a new study finds.

Compared with rivaroxaban, apixaban cut risks nearly in half, suggesting that clinicians should consider these new data when choosing an anticoagulant, reported lead author Ghadeer K. Dawwas, PhD, of the University of Pennsylvania, Philadelphia, and colleagues.

In the new retrospective study involving almost 20,000 patients, Dr. Dawwas and her colleagues “emulated a target trial” using private insurance claims from Optum’s deidentified Clinformatics Data Mart Database. The cohort was narrowed from a screened population of 58,210 patients with concurrent AFib and VHD to 9,947 new apixaban users who could be closely matched with 9,947 new rivaroxaban users. Covariates included provider specialty, type of VHD, demographic characteristics, measures of health care use, baseline use of medications, and baseline comorbidities.

The primary effectiveness outcome was a composite of systemic embolism and ischemic stroke, while the primary safety outcome was a composite of intracranial or gastrointestinal bleeding.

“Although several ongoing trials aim to compare apixaban with warfarin in patients with AFib and VHD, none of these trials will directly compare apixaban and rivaroxaban,” the investigators wrote. Their report is in Annals of Internal Medicine.

Dr. Dawwas and colleagues previously showed that direct oral anticoagulants (DOACs) were safer and more effective than warfarin in the same patient population. Comparing apixaban and rivaroxaban – the two most common DOACs – was the next logical step, Dr. Dawwas said in an interview.
 

Study results

Compared with rivaroxaban, patients who received apixaban had a 43% reduced risk of stroke or embolism (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.40-0.80). Apixaban’s ability to protect against bleeding appeared even more pronounced, with a 49% reduced risk over rivaroxaban (HR, 0.51; 95% CI, 0.41-0.62).

Comparing the two agents on an absolute basis, apixaban reduced risk of embolism or stroke by 0.2% within the first 6 months of treatment initiation, and 1.1% within the first year of initiation. At the same time points, absolute risk reductions for bleeding were 1.2% and 1.9%, respectively.

The investigators noted that their results held consistent in an alternative analysis that considered separate types of VHD.

“Based on the results from our analysis, we showed that apixaban is effective and safe in patients with atrial fibrillation and valvular heart diseases,” Dr. Dawwas said.
 

Head-to-head trial needed to change practice

Christopher M. Bianco, DO, associate professor of medicine at West Virginia University Heart and Vascular Institute, Morgantown, said the findings “add to the growing body of literature,” but “a head-to-head trial would be necessary to make a definitive change to clinical practice.”

Dr. Bianco, who recently conducted a retrospective analysis of apixaban and rivaroxaban that found no difference in safety and efficacy among a different patient population, said these kinds of studies are helpful in generating hypotheses, but they can’t account for all relevant clinical factors.

“There are just so many things that go into the decision-making process of [prescribing] apixaban and rivaroxaban,” he said. “Even though [Dr. Dawwas and colleagues] used propensity matching, you’re never going to be able to sort that out with a retrospective analysis.”

Specifically, Dr. Bianco noted that the findings did not include dose data. This is a key gap, he said, considering how often real-world datasets have shown that providers underdose DOACs for a number of unaccountable reasons, and how frequently patients exhibit poor adherence.

The study also lacked detail concerning the degree of renal dysfunction, which can determine drug eligibility, Dr. Bianco said. Furthermore, attempts to stratify patients based on thrombosis and bleeding risk were likely “insufficient,” he added.

Dr. Bianco also cautioned that the investigators defined valvular heart disease as any valve-related disease of any severity. In contrast, previous studies have generally restricted valvular heart disease to patients with mitral stenosis or prosthetic valves.

“This is definitely not the traditional definition of valvular heart disease, so the title is a little bit misleading in that sense, although they certainly do disclose that in the methods,” Dr. Bianco said.

On a more positive note, he highlighted the size of the patient population, and the real-world data, which included many patients who would be excluded from clinical trials.

More broadly, the study helps drive research forward, Dr. Bianco concluded; namely, by attracting financial support for a more powerful head-to-head trial that drug makers are unlikely to fund due to inherent market risk.

This study was supported by the National Institutes of Health. The investigators disclosed additional relationships with Takeda, Spark, Sanofi, and others. Dr. Bianco disclosed no conflicts of interest.

Apixaban offers greater protection than rivaroxaban against ischemic stroke, systemic embolism, and bleeding in patients with both atrial fibrillation (AFib) and valvular heart disease (VHD), a new study finds.

Compared with rivaroxaban, apixaban cut risks nearly in half, suggesting that clinicians should consider these new data when choosing an anticoagulant, reported lead author Ghadeer K. Dawwas, PhD, of the University of Pennsylvania, Philadelphia, and colleagues.

In the new retrospective study involving almost 20,000 patients, Dr. Dawwas and her colleagues “emulated a target trial” using private insurance claims from Optum’s deidentified Clinformatics Data Mart Database. The cohort was narrowed from a screened population of 58,210 patients with concurrent AFib and VHD to 9,947 new apixaban users who could be closely matched with 9,947 new rivaroxaban users. Covariates included provider specialty, type of VHD, demographic characteristics, measures of health care use, baseline use of medications, and baseline comorbidities.

The primary effectiveness outcome was a composite of systemic embolism and ischemic stroke, while the primary safety outcome was a composite of intracranial or gastrointestinal bleeding.

“Although several ongoing trials aim to compare apixaban with warfarin in patients with AFib and VHD, none of these trials will directly compare apixaban and rivaroxaban,” the investigators wrote. Their report is in Annals of Internal Medicine.

Dr. Dawwas and colleagues previously showed that direct oral anticoagulants (DOACs) were safer and more effective than warfarin in the same patient population. Comparing apixaban and rivaroxaban – the two most common DOACs – was the next logical step, Dr. Dawwas said in an interview.
 

Study results

Compared with rivaroxaban, patients who received apixaban had a 43% reduced risk of stroke or embolism (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.40-0.80). Apixaban’s ability to protect against bleeding appeared even more pronounced, with a 49% reduced risk over rivaroxaban (HR, 0.51; 95% CI, 0.41-0.62).

Comparing the two agents on an absolute basis, apixaban reduced risk of embolism or stroke by 0.2% within the first 6 months of treatment initiation, and 1.1% within the first year of initiation. At the same time points, absolute risk reductions for bleeding were 1.2% and 1.9%, respectively.

The investigators noted that their results held consistent in an alternative analysis that considered separate types of VHD.

“Based on the results from our analysis, we showed that apixaban is effective and safe in patients with atrial fibrillation and valvular heart diseases,” Dr. Dawwas said.
 

Head-to-head trial needed to change practice

Christopher M. Bianco, DO, associate professor of medicine at West Virginia University Heart and Vascular Institute, Morgantown, said the findings “add to the growing body of literature,” but “a head-to-head trial would be necessary to make a definitive change to clinical practice.”

Dr. Bianco, who recently conducted a retrospective analysis of apixaban and rivaroxaban that found no difference in safety and efficacy among a different patient population, said these kinds of studies are helpful in generating hypotheses, but they can’t account for all relevant clinical factors.

“There are just so many things that go into the decision-making process of [prescribing] apixaban and rivaroxaban,” he said. “Even though [Dr. Dawwas and colleagues] used propensity matching, you’re never going to be able to sort that out with a retrospective analysis.”

Specifically, Dr. Bianco noted that the findings did not include dose data. This is a key gap, he said, considering how often real-world datasets have shown that providers underdose DOACs for a number of unaccountable reasons, and how frequently patients exhibit poor adherence.

The study also lacked detail concerning the degree of renal dysfunction, which can determine drug eligibility, Dr. Bianco said. Furthermore, attempts to stratify patients based on thrombosis and bleeding risk were likely “insufficient,” he added.

Dr. Bianco also cautioned that the investigators defined valvular heart disease as any valve-related disease of any severity. In contrast, previous studies have generally restricted valvular heart disease to patients with mitral stenosis or prosthetic valves.

“This is definitely not the traditional definition of valvular heart disease, so the title is a little bit misleading in that sense, although they certainly do disclose that in the methods,” Dr. Bianco said.

On a more positive note, he highlighted the size of the patient population, and the real-world data, which included many patients who would be excluded from clinical trials.

More broadly, the study helps drive research forward, Dr. Bianco concluded; namely, by attracting financial support for a more powerful head-to-head trial that drug makers are unlikely to fund due to inherent market risk.

This study was supported by the National Institutes of Health. The investigators disclosed additional relationships with Takeda, Spark, Sanofi, and others. Dr. Bianco disclosed no conflicts of interest.

Exposure to air pollution not only raises stroke risk, but it is also tied to poor post-stroke outcomes, including death. Results of a UK biobank study show high levels of air pollution were associated with an increased risk of transition from health to a first stroke and subsequent progression to cardiovascular (CV) events and death.

“These results indicate that understanding and reducing the effects of air pollutants on different transition stages in stroke will be beneficial in managing people’s health and preventing the occurrence and progression of stroke,” study investigator Hualiang Lin, PhD, of Sun Yat-sen University School of Public Health, Guangzhou, China, said in a news release.

The study was published online  in the journal Neurology.
 

A way to stop stroke progression?

The researchers assessed air pollution exposure in 318,752 people (mean age, 56) from the UK biobank database. None had a history of stroke or heart disease at the start of the study. Annual concentrations of air pollution near where people lived were estimated through land-use regressions.

During an average follow-up of 12 years, 5,967 people had a stroke, 2,985 developed post-stroke CVD, and 1,020 died.

After adjusting for confounding factors, every 5 µg/m³ increase in exposure to fine particulate matter (PM_2.5) was associated with a 24% increase in transition from healthy to first stroke (hazard ratio, 1.24; 95% confidence interval, 1.10-1.40) and a 30% increase in transition from being healthy to dying (HR, 1.30; 95% CI, 1.21-1.40).

PM_2.5 is less than 2.5 microns in diameter and includes fly ash from coal combustion. The World Health Organization recommends that annual PM_2.5 exposure should not exceed 5 µg/m³.

Those who had a stroke during the study had an average exposure of 10.03 µg/m³ of PM_2.5, compared with 9.97 µg/m³ for those who did not have a stroke.

The air pollutants nitrogen oxide and nitrogen dioxide were also associated with an increased risk of stroke and death, but the associations were weaker.

“More research is needed, but it’s possible that decreasing exposure to heavy levels of air pollution could play a role in reducing the progression of stroke,” Dr. Lin said.

“People can reduce their exposure by staying indoors on heavy pollution days, reducing their outdoor exercise, wearing masks to filter out particulate matter, and using air purifiers,” Dr. Lin added.

Public policy implications

Reached for comment, Steffen E. Petersen, MD, MPH, professor of cardiovascular medicine, Barts Health NHS Trust, London, said the study “elegantly confirms the increased risk of stroke due to air pollution in the UK Biobank population study but interestingly suggests that the impact of air pollution may continue to adversely impact cardiovascular health even after the stroke occurred.”

“This is further evidence to inform policymakers to tackle air pollution and get levels below the recommended levels,” Dr. Petersen said.

“On a personal level, everyone, including stroke patients, may wish to consider personal measures to reduce exposure to air pollution, such as avoiding walking along polluted streets and rather take a less polluted route away from the main roads,” Dr. Petersen added.

The study had no targeted funding. Dr. Lin and Dr. Petersen report no relevant financial relationships.

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

Exposure to air pollution not only raises stroke risk, but it is also tied to poor post-stroke outcomes, including death. Results of a UK biobank study show high levels of air pollution were associated with an increased risk of transition from health to a first stroke and subsequent progression to cardiovascular (CV) events and death.

“These results indicate that understanding and reducing the effects of air pollutants on different transition stages in stroke will be beneficial in managing people’s health and preventing the occurrence and progression of stroke,” study investigator Hualiang Lin, PhD, of Sun Yat-sen University School of Public Health, Guangzhou, China, said in a news release.

The study was published online  in the journal Neurology.
 

A way to stop stroke progression?

The researchers assessed air pollution exposure in 318,752 people (mean age, 56) from the UK biobank database. None had a history of stroke or heart disease at the start of the study. Annual concentrations of air pollution near where people lived were estimated through land-use regressions.

During an average follow-up of 12 years, 5,967 people had a stroke, 2,985 developed post-stroke CVD, and 1,020 died.

After adjusting for confounding factors, every 5 µg/m³ increase in exposure to fine particulate matter (PM_2.5) was associated with a 24% increase in transition from healthy to first stroke (hazard ratio, 1.24; 95% confidence interval, 1.10-1.40) and a 30% increase in transition from being healthy to dying (HR, 1.30; 95% CI, 1.21-1.40).

PM_2.5 is less than 2.5 microns in diameter and includes fly ash from coal combustion. The World Health Organization recommends that annual PM_2.5 exposure should not exceed 5 µg/m³.

Those who had a stroke during the study had an average exposure of 10.03 µg/m³ of PM_2.5, compared with 9.97 µg/m³ for those who did not have a stroke.

The air pollutants nitrogen oxide and nitrogen dioxide were also associated with an increased risk of stroke and death, but the associations were weaker.

“More research is needed, but it’s possible that decreasing exposure to heavy levels of air pollution could play a role in reducing the progression of stroke,” Dr. Lin said.

“People can reduce their exposure by staying indoors on heavy pollution days, reducing their outdoor exercise, wearing masks to filter out particulate matter, and using air purifiers,” Dr. Lin added.

Public policy implications

Reached for comment, Steffen E. Petersen, MD, MPH, professor of cardiovascular medicine, Barts Health NHS Trust, London, said the study “elegantly confirms the increased risk of stroke due to air pollution in the UK Biobank population study but interestingly suggests that the impact of air pollution may continue to adversely impact cardiovascular health even after the stroke occurred.”

“This is further evidence to inform policymakers to tackle air pollution and get levels below the recommended levels,” Dr. Petersen said.

“On a personal level, everyone, including stroke patients, may wish to consider personal measures to reduce exposure to air pollution, such as avoiding walking along polluted streets and rather take a less polluted route away from the main roads,” Dr. Petersen added.

The study had no targeted funding. Dr. Lin and Dr. Petersen report no relevant financial relationships.

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

Exposure to air pollution not only raises stroke risk, but it is also tied to poor post-stroke outcomes, including death. Results of a UK biobank study show high levels of air pollution were associated with an increased risk of transition from health to a first stroke and subsequent progression to cardiovascular (CV) events and death.

“These results indicate that understanding and reducing the effects of air pollutants on different transition stages in stroke will be beneficial in managing people’s health and preventing the occurrence and progression of stroke,” study investigator Hualiang Lin, PhD, of Sun Yat-sen University School of Public Health, Guangzhou, China, said in a news release.

The study was published online  in the journal Neurology.
 

A way to stop stroke progression?

The researchers assessed air pollution exposure in 318,752 people (mean age, 56) from the UK biobank database. None had a history of stroke or heart disease at the start of the study. Annual concentrations of air pollution near where people lived were estimated through land-use regressions.

During an average follow-up of 12 years, 5,967 people had a stroke, 2,985 developed post-stroke CVD, and 1,020 died.

After adjusting for confounding factors, every 5 µg/m³ increase in exposure to fine particulate matter (PM_2.5) was associated with a 24% increase in transition from healthy to first stroke (hazard ratio, 1.24; 95% confidence interval, 1.10-1.40) and a 30% increase in transition from being healthy to dying (HR, 1.30; 95% CI, 1.21-1.40).

PM_2.5 is less than 2.5 microns in diameter and includes fly ash from coal combustion. The World Health Organization recommends that annual PM_2.5 exposure should not exceed 5 µg/m³.

Those who had a stroke during the study had an average exposure of 10.03 µg/m³ of PM_2.5, compared with 9.97 µg/m³ for those who did not have a stroke.

The air pollutants nitrogen oxide and nitrogen dioxide were also associated with an increased risk of stroke and death, but the associations were weaker.

“More research is needed, but it’s possible that decreasing exposure to heavy levels of air pollution could play a role in reducing the progression of stroke,” Dr. Lin said.

“People can reduce their exposure by staying indoors on heavy pollution days, reducing their outdoor exercise, wearing masks to filter out particulate matter, and using air purifiers,” Dr. Lin added.

Public policy implications

Reached for comment, Steffen E. Petersen, MD, MPH, professor of cardiovascular medicine, Barts Health NHS Trust, London, said the study “elegantly confirms the increased risk of stroke due to air pollution in the UK Biobank population study but interestingly suggests that the impact of air pollution may continue to adversely impact cardiovascular health even after the stroke occurred.”

“This is further evidence to inform policymakers to tackle air pollution and get levels below the recommended levels,” Dr. Petersen said.

“On a personal level, everyone, including stroke patients, may wish to consider personal measures to reduce exposure to air pollution, such as avoiding walking along polluted streets and rather take a less polluted route away from the main roads,” Dr. Petersen added.

The study had no targeted funding. Dr. Lin and Dr. Petersen report no relevant financial relationships.

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

Shortening the duration of dual-antiplatelet therapy (DAPT) and continuing with a P2Y12 inhibitor alone after percutaneous coronary intervention (PCI) was associated with a similar rate of ischemic events but with less bleeding than prolonged DAPT after 3 years of follow-up in the SMART-CHOICE trial.

“The current results of extended follow-up from the SMART-CHOICE trial support evidence of an aspirin dropping strategy with indefinite use of P2Y12 inhibitor after minimum use of DAPT in patients who underwent PCI,” the investigators, with lead author Ki Hong Choi, MD, division of cardiology, department of medicine, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea, conclude.

The 3-year results from the study were published online in JAMA Cardiology.

The authors explain that although dual therapy with aspirin and a P2Y12 inhibitor after PCI with a drug-eluting stent (DES) is crucial to reduce the risk of ischemic events, it raises concerns about increased risk of bleeding, and the antiplatelet strategy after PCI is currently shifting to reduce the duration of DAPT.

Several recent randomized studies have consistently shown that a short duration of DAPT (1-3 months) followed by P2Y12 inhibitor monotherapy had ischemia protection effects comparable with that of DAPT of longer duration, and it was associated with a significantly reduced risk of bleeding events in patients who underwent PCI, they note. However, these studies have so far reported only 1-year outcomes, and long-term results are not yet available.

The SMART-CHOICE trial compared two antiplatelet strategies – 3 months of DAPT followed by long-term P2Y12 inhibitor monotherapy (mainly with clopidogrel) or prolonged DAPT for 12 months or longer – in 2,993 patients who had undergone PCI with a drug-eluting stent. Results at 12 months showed a similar rate of ischemic events with both strategies but a lower rate of bleeding in the group that received shortened DAPT.

The SMART-CHOICE investigators now report the 3-year results showing similar outcomes.

At 3 years, the primary endpoint, a composite of all-cause death, myocardial infarction, or stroke, had occurred in 6.3% of the shortened DAPT group and 6.1% in the prolonged DAPT group, giving a hazard ratio of 1.06 (95% confidence interval, 0.79-1.44).

But in the shortened DAPT group, the risk of bleeding was reduced. Bleeding Academic Research Consortium (BARC) types 2-5 bleeding had occurred in 3.2% of the shortened DAPT group and in 8.2% of the prolonged DAPT group (hazard ratio, 0.39; 95% CI, 0.28-0.55). Major bleeding, BARC types 3-5, occurred in 1.2% of the shortened DAPT group and in 2.4% of the prolonged DAPT group (HR, 0.56; 95% CI 0.31-0.99).

The landmark analyses between 3 months and 3 years and per-protocol analyses showed consistent results.

The researchers point out that this is the first trial to report on the long-term safety and efficacy of P2Y12-inhibitor monotherapy as long-term maintenance therapy for stable patients treated with PCI.

“Especially considering that extended DAPT significantly reduced the risks of ischemic events compared with aspirin monotherapy in a couple of trials, comparison between P2Y12-inhibitor monotherapy and prolonged DAPT for recurrent ischemic events over a longer period beyond 1 year is of great importance,” they say.

They cite two other trials – HOST-EXAM and GLOBAL LEADERS – which have shown P2Y12-inhibitor monotherapy to be superior to aspirin monotherapy in preventing both ischemic and bleeding events during the long-term maintenance period after PCI.

“Combining the results of the current study, HOST-EXAM trial, and landmark analysis of the GLOBAL LEADERS trial, long-term P2Y12-inhibitor monotherapy after a minimum period of DAPT might be the most reliable option from among aspirin monotherapy, P2Y12 monotherapy, and extended DAPT for maintenance therapy after stabilizing patients who have undergone PCI with a current-generation DES,” they conclude.

They note that the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions guidelines for coronary artery revascularization newly recommends a shorter course of DAPT followed by P2Y12 monotherapy as a class IIa indication. The recommendation is based on results of five large, randomized clinical trials, including SMART-CHOICE, TWILIGHT, STOPDAPT-2, TICO, and GLOBAL LEADERS.

“The current results of extended follow-up from the SMART-CHOICE trial support evidence of aspirin-dropping strategy with indefinite use of P2Y12 inhibitor after minimum use of DAPT in patients who underwent PCI,” they say.

They point out that two further trials, A-CLOSE in high-risk patients and SMART-CHOICE III, will be helpful to confirm these findings.
 

P2Y12-inhibitor monotherapy ‘attractive concept’

In an accompanying editor’s note, Ajay Kirtane, MD, Columbia University Irving Medical Center/New York–Presbyterian Hospital, New York, and Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai and the Cardiovascular Research Foundation, New York, note that current guidelines recommend 3-6 months of DAPT following PCI with current-generation drug-eluting stents in stable patients and 6-12 months or longer for those with acute coronary syndromes. For patients at higher risk of bleeding, even shorter DAPT durations can be considered on a case-by-case basis.

Historically, the component of DAPT subject to discontinuation decisions was the P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor), but more recent trials have further explored whether discontinuation of the aspirin component of DAPT can mitigate bleeding while preserving anti-ischemic efficacy.

The editorialists explain that the concept of P2Y1-inhibitor monotherapy is attractive because it may optimize antiplatelet effects through a single agent that can avoid the gastrointestinal toxicity of aspirin as well as the increased bleeding that comes with combing multiple antithrombotic agents.

They suggest that the long-term results from the SMART-CHOICE trial “should lead clinicians to consider a strategy of monotherapy after a short period of DAPT as a viable one to mitigate bleeding risk,” although they also point out that SMART-CHOICE was underpowered to rigorously assess ischemic differences, so caution is warranted.

“For patients at greatest risk for recurrent ischemic events, the role of continued DAPT is always an option, but these data (and other consistent trials) give clinicians more options to pursue individualized treatment decisions,” they write.

“To some, the continually moving field of post-PCI antiplatelet therapy has provided too many choices, which can at times be dizzying. To us, every patient is different, and thoughtful evidence-based consideration is increasingly possible for many of our treatment decisions,” they conclude.

The SMART-CHOICE study was supported by unrestricted grants from the Korean Society of Interventional Cardiology, Abbott Vascular, Biotronik, and Boston Scientific.

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

Shortening the duration of dual-antiplatelet therapy (DAPT) and continuing with a P2Y12 inhibitor alone after percutaneous coronary intervention (PCI) was associated with a similar rate of ischemic events but with less bleeding than prolonged DAPT after 3 years of follow-up in the SMART-CHOICE trial.

“The current results of extended follow-up from the SMART-CHOICE trial support evidence of an aspirin dropping strategy with indefinite use of P2Y12 inhibitor after minimum use of DAPT in patients who underwent PCI,” the investigators, with lead author Ki Hong Choi, MD, division of cardiology, department of medicine, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea, conclude.

The 3-year results from the study were published online in JAMA Cardiology.

The authors explain that although dual therapy with aspirin and a P2Y12 inhibitor after PCI with a drug-eluting stent (DES) is crucial to reduce the risk of ischemic events, it raises concerns about increased risk of bleeding, and the antiplatelet strategy after PCI is currently shifting to reduce the duration of DAPT.

Several recent randomized studies have consistently shown that a short duration of DAPT (1-3 months) followed by P2Y12 inhibitor monotherapy had ischemia protection effects comparable with that of DAPT of longer duration, and it was associated with a significantly reduced risk of bleeding events in patients who underwent PCI, they note. However, these studies have so far reported only 1-year outcomes, and long-term results are not yet available.

The SMART-CHOICE trial compared two antiplatelet strategies – 3 months of DAPT followed by long-term P2Y12 inhibitor monotherapy (mainly with clopidogrel) or prolonged DAPT for 12 months or longer – in 2,993 patients who had undergone PCI with a drug-eluting stent. Results at 12 months showed a similar rate of ischemic events with both strategies but a lower rate of bleeding in the group that received shortened DAPT.

The SMART-CHOICE investigators now report the 3-year results showing similar outcomes.

At 3 years, the primary endpoint, a composite of all-cause death, myocardial infarction, or stroke, had occurred in 6.3% of the shortened DAPT group and 6.1% in the prolonged DAPT group, giving a hazard ratio of 1.06 (95% confidence interval, 0.79-1.44).

But in the shortened DAPT group, the risk of bleeding was reduced. Bleeding Academic Research Consortium (BARC) types 2-5 bleeding had occurred in 3.2% of the shortened DAPT group and in 8.2% of the prolonged DAPT group (hazard ratio, 0.39; 95% CI, 0.28-0.55). Major bleeding, BARC types 3-5, occurred in 1.2% of the shortened DAPT group and in 2.4% of the prolonged DAPT group (HR, 0.56; 95% CI 0.31-0.99).

The landmark analyses between 3 months and 3 years and per-protocol analyses showed consistent results.

The researchers point out that this is the first trial to report on the long-term safety and efficacy of P2Y12-inhibitor monotherapy as long-term maintenance therapy for stable patients treated with PCI.

“Especially considering that extended DAPT significantly reduced the risks of ischemic events compared with aspirin monotherapy in a couple of trials, comparison between P2Y12-inhibitor monotherapy and prolonged DAPT for recurrent ischemic events over a longer period beyond 1 year is of great importance,” they say.

They cite two other trials – HOST-EXAM and GLOBAL LEADERS – which have shown P2Y12-inhibitor monotherapy to be superior to aspirin monotherapy in preventing both ischemic and bleeding events during the long-term maintenance period after PCI.

“Combining the results of the current study, HOST-EXAM trial, and landmark analysis of the GLOBAL LEADERS trial, long-term P2Y12-inhibitor monotherapy after a minimum period of DAPT might be the most reliable option from among aspirin monotherapy, P2Y12 monotherapy, and extended DAPT for maintenance therapy after stabilizing patients who have undergone PCI with a current-generation DES,” they conclude.

They note that the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions guidelines for coronary artery revascularization newly recommends a shorter course of DAPT followed by P2Y12 monotherapy as a class IIa indication. The recommendation is based on results of five large, randomized clinical trials, including SMART-CHOICE, TWILIGHT, STOPDAPT-2, TICO, and GLOBAL LEADERS.

“The current results of extended follow-up from the SMART-CHOICE trial support evidence of aspirin-dropping strategy with indefinite use of P2Y12 inhibitor after minimum use of DAPT in patients who underwent PCI,” they say.

They point out that two further trials, A-CLOSE in high-risk patients and SMART-CHOICE III, will be helpful to confirm these findings.
 

P2Y12-inhibitor monotherapy ‘attractive concept’

In an accompanying editor’s note, Ajay Kirtane, MD, Columbia University Irving Medical Center/New York–Presbyterian Hospital, New York, and Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai and the Cardiovascular Research Foundation, New York, note that current guidelines recommend 3-6 months of DAPT following PCI with current-generation drug-eluting stents in stable patients and 6-12 months or longer for those with acute coronary syndromes. For patients at higher risk of bleeding, even shorter DAPT durations can be considered on a case-by-case basis.

Historically, the component of DAPT subject to discontinuation decisions was the P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor), but more recent trials have further explored whether discontinuation of the aspirin component of DAPT can mitigate bleeding while preserving anti-ischemic efficacy.

The editorialists explain that the concept of P2Y1-inhibitor monotherapy is attractive because it may optimize antiplatelet effects through a single agent that can avoid the gastrointestinal toxicity of aspirin as well as the increased bleeding that comes with combing multiple antithrombotic agents.

They suggest that the long-term results from the SMART-CHOICE trial “should lead clinicians to consider a strategy of monotherapy after a short period of DAPT as a viable one to mitigate bleeding risk,” although they also point out that SMART-CHOICE was underpowered to rigorously assess ischemic differences, so caution is warranted.

“For patients at greatest risk for recurrent ischemic events, the role of continued DAPT is always an option, but these data (and other consistent trials) give clinicians more options to pursue individualized treatment decisions,” they write.

“To some, the continually moving field of post-PCI antiplatelet therapy has provided too many choices, which can at times be dizzying. To us, every patient is different, and thoughtful evidence-based consideration is increasingly possible for many of our treatment decisions,” they conclude.

The SMART-CHOICE study was supported by unrestricted grants from the Korean Society of Interventional Cardiology, Abbott Vascular, Biotronik, and Boston Scientific.

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

Shortening the duration of dual-antiplatelet therapy (DAPT) and continuing with a P2Y12 inhibitor alone after percutaneous coronary intervention (PCI) was associated with a similar rate of ischemic events but with less bleeding than prolonged DAPT after 3 years of follow-up in the SMART-CHOICE trial.

“The current results of extended follow-up from the SMART-CHOICE trial support evidence of an aspirin dropping strategy with indefinite use of P2Y12 inhibitor after minimum use of DAPT in patients who underwent PCI,” the investigators, with lead author Ki Hong Choi, MD, division of cardiology, department of medicine, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea, conclude.

The 3-year results from the study were published online in JAMA Cardiology.

The authors explain that although dual therapy with aspirin and a P2Y12 inhibitor after PCI with a drug-eluting stent (DES) is crucial to reduce the risk of ischemic events, it raises concerns about increased risk of bleeding, and the antiplatelet strategy after PCI is currently shifting to reduce the duration of DAPT.

Several recent randomized studies have consistently shown that a short duration of DAPT (1-3 months) followed by P2Y12 inhibitor monotherapy had ischemia protection effects comparable with that of DAPT of longer duration, and it was associated with a significantly reduced risk of bleeding events in patients who underwent PCI, they note. However, these studies have so far reported only 1-year outcomes, and long-term results are not yet available.

The SMART-CHOICE trial compared two antiplatelet strategies – 3 months of DAPT followed by long-term P2Y12 inhibitor monotherapy (mainly with clopidogrel) or prolonged DAPT for 12 months or longer – in 2,993 patients who had undergone PCI with a drug-eluting stent. Results at 12 months showed a similar rate of ischemic events with both strategies but a lower rate of bleeding in the group that received shortened DAPT.

The SMART-CHOICE investigators now report the 3-year results showing similar outcomes.

At 3 years, the primary endpoint, a composite of all-cause death, myocardial infarction, or stroke, had occurred in 6.3% of the shortened DAPT group and 6.1% in the prolonged DAPT group, giving a hazard ratio of 1.06 (95% confidence interval, 0.79-1.44).

But in the shortened DAPT group, the risk of bleeding was reduced. Bleeding Academic Research Consortium (BARC) types 2-5 bleeding had occurred in 3.2% of the shortened DAPT group and in 8.2% of the prolonged DAPT group (hazard ratio, 0.39; 95% CI, 0.28-0.55). Major bleeding, BARC types 3-5, occurred in 1.2% of the shortened DAPT group and in 2.4% of the prolonged DAPT group (HR, 0.56; 95% CI 0.31-0.99).

The landmark analyses between 3 months and 3 years and per-protocol analyses showed consistent results.

The researchers point out that this is the first trial to report on the long-term safety and efficacy of P2Y12-inhibitor monotherapy as long-term maintenance therapy for stable patients treated with PCI.

“Especially considering that extended DAPT significantly reduced the risks of ischemic events compared with aspirin monotherapy in a couple of trials, comparison between P2Y12-inhibitor monotherapy and prolonged DAPT for recurrent ischemic events over a longer period beyond 1 year is of great importance,” they say.

They cite two other trials – HOST-EXAM and GLOBAL LEADERS – which have shown P2Y12-inhibitor monotherapy to be superior to aspirin monotherapy in preventing both ischemic and bleeding events during the long-term maintenance period after PCI.

“Combining the results of the current study, HOST-EXAM trial, and landmark analysis of the GLOBAL LEADERS trial, long-term P2Y12-inhibitor monotherapy after a minimum period of DAPT might be the most reliable option from among aspirin monotherapy, P2Y12 monotherapy, and extended DAPT for maintenance therapy after stabilizing patients who have undergone PCI with a current-generation DES,” they conclude.

They note that the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions guidelines for coronary artery revascularization newly recommends a shorter course of DAPT followed by P2Y12 monotherapy as a class IIa indication. The recommendation is based on results of five large, randomized clinical trials, including SMART-CHOICE, TWILIGHT, STOPDAPT-2, TICO, and GLOBAL LEADERS.

“The current results of extended follow-up from the SMART-CHOICE trial support evidence of aspirin-dropping strategy with indefinite use of P2Y12 inhibitor after minimum use of DAPT in patients who underwent PCI,” they say.

They point out that two further trials, A-CLOSE in high-risk patients and SMART-CHOICE III, will be helpful to confirm these findings.
 

P2Y12-inhibitor monotherapy ‘attractive concept’

In an accompanying editor’s note, Ajay Kirtane, MD, Columbia University Irving Medical Center/New York–Presbyterian Hospital, New York, and Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai and the Cardiovascular Research Foundation, New York, note that current guidelines recommend 3-6 months of DAPT following PCI with current-generation drug-eluting stents in stable patients and 6-12 months or longer for those with acute coronary syndromes. For patients at higher risk of bleeding, even shorter DAPT durations can be considered on a case-by-case basis.

Historically, the component of DAPT subject to discontinuation decisions was the P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor), but more recent trials have further explored whether discontinuation of the aspirin component of DAPT can mitigate bleeding while preserving anti-ischemic efficacy.

The editorialists explain that the concept of P2Y1-inhibitor monotherapy is attractive because it may optimize antiplatelet effects through a single agent that can avoid the gastrointestinal toxicity of aspirin as well as the increased bleeding that comes with combing multiple antithrombotic agents.

They suggest that the long-term results from the SMART-CHOICE trial “should lead clinicians to consider a strategy of monotherapy after a short period of DAPT as a viable one to mitigate bleeding risk,” although they also point out that SMART-CHOICE was underpowered to rigorously assess ischemic differences, so caution is warranted.

“For patients at greatest risk for recurrent ischemic events, the role of continued DAPT is always an option, but these data (and other consistent trials) give clinicians more options to pursue individualized treatment decisions,” they write.

“To some, the continually moving field of post-PCI antiplatelet therapy has provided too many choices, which can at times be dizzying. To us, every patient is different, and thoughtful evidence-based consideration is increasingly possible for many of our treatment decisions,” they conclude.

The SMART-CHOICE study was supported by unrestricted grants from the Korean Society of Interventional Cardiology, Abbott Vascular, Biotronik, and Boston Scientific.

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