Anticoagulation Hub

LOS ANGELES – Endovascular thrombectomy is not only clinically the best option for many patients with acute, ischemic strokes involving a proximal occlusion in a large cerebral artery; it’s also highly cost effective, based on follow-up analyses of two of the five randomized trials published in 2015 that collectively established thrombectomy as standard of care for these patients.

Thrombectomy plus administration of intravenous tissue plasminogen activator (TPA), compared with TPA only, “is highly cost effective and economically dominant with lower long-term cost and better outcomes,” Theresa I. Shireman, Ph.D., said at the International Stroke Conference.

And in an independent analysis of data from a totally different trial, endovascular thrombectomy on average reduced patients’ acute length of hospitalization, improved their survival and quality of life, and was cost saving when compared with treatment with intravenous TPA only, which had previously been the standard of care, Dr. Bruce C.V. Campbell reported at the meeting.

The analysis presented by Dr. Shireman used data collected in the SWIFT-PRIME trial, which randomized 196 patients at centers in the United States and Europe to treatment with either intravenous TPA plus endovascular thrombectomy or TPA alone. Average total costs during the index hospitalization ran to roughly $46,000 in the combined-treatment arm and about $29,000 in the TPA-only arm, a difference largely driven by a roughly $15,000 average incremental cost for the thrombectomy procedure, said Dr. Shireman, professor of health services research at Brown University in Providence, R.I.

However, the cost-effectiveness of thrombectomy began to kick in soon after. During the 90 days following index hospitalization, patients who underwent thrombectomy had substantial average reductions in their need for inpatient rehabilitation, time spent in skilled nursing facilities, and in outpatient rehabilitation. Overall, total medical costs during the first 90 days post discharge ran on average close to $5,000 less per patient following thrombectomy. In addition, based on their health status after 90 days, patients treated with thrombectomy were projected to have a greater than 1.7-year average life expectancy than those randomized to TPA only, with a projected net gain of 1.74 quality-adjusted life years (QALY) per patient and with a projected average decrease of roughly $23,000 in total lifetime medical costs.

Based on this average increase in QALYs and decreased long-term cost, adding thrombectomy to TPA for routine treatment of the types of patients enrolled in SWIFT-PRIME was economically dominant, Dr. Shireman said at the meeting sponsored by the American Heart Association. She also projected that despite the higher upfront cost for adding thrombectomy to treatment, the eventual savings in long-term care meant that thrombectomy began producing a net saving once patients survived for more than 22 months following their index hospitalization.

Dr. Campbell reported very similar findings in his analysis of data collected from the EXTEND-IA trial, which randomized 70 patients at 10 centers in Australia and New Zealand. During the first 90 days of treatment, including the index hospitalization, treatment with thrombectomy plus TPA saved an average of roughly $4,000 U.S.per patient, compared with TPA only, even though the average incremental cost for adding thrombectomy was nearly $11,000 U.S. The overall increased total 90-day costs with TPA only was largely driven by a substantially longer time spent hospitalized among the TPA-only patients, compared with those treated with thrombectomy plus TPA, said Dr. Campbell, a neurologist and head of hyperacute stroke at Royal Melbourne Hospital.

In addition, adding thrombectomy resulted in a projected average 4-year increase in life expectancy, and an average gain of about 3 QALYs per patient. Thrombectomy “is an incredibly powerful procedure, not just in terms of clinical response but also in terms of economics,” he concluded. Even when judged by the worst-case scenario of the analysis, “there is a 100% probability that the cost-effectiveness per QALY is less than $10,000 U.S., which is incredible value,” Dr. Campbell said.

SWIFT-PRIME was sponsored by Covidien/Medtronic. EXTEND-IA received partial funding through an unrestricted grant from Covidien/Medtronic. Dr. Shireman and Dr. Campbell had no personal disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

LOS ANGELES – Endovascular thrombectomy is not only clinically the best option for many patients with acute, ischemic strokes involving a proximal occlusion in a large cerebral artery; it’s also highly cost effective, based on follow-up analyses of two of the five randomized trials published in 2015 that collectively established thrombectomy as standard of care for these patients.

Thrombectomy plus administration of intravenous tissue plasminogen activator (TPA), compared with TPA only, “is highly cost effective and economically dominant with lower long-term cost and better outcomes,” Theresa I. Shireman, Ph.D., said at the International Stroke Conference.

And in an independent analysis of data from a totally different trial, endovascular thrombectomy on average reduced patients’ acute length of hospitalization, improved their survival and quality of life, and was cost saving when compared with treatment with intravenous TPA only, which had previously been the standard of care, Dr. Bruce C.V. Campbell reported at the meeting.

The analysis presented by Dr. Shireman used data collected in the SWIFT-PRIME trial, which randomized 196 patients at centers in the United States and Europe to treatment with either intravenous TPA plus endovascular thrombectomy or TPA alone. Average total costs during the index hospitalization ran to roughly $46,000 in the combined-treatment arm and about $29,000 in the TPA-only arm, a difference largely driven by a roughly $15,000 average incremental cost for the thrombectomy procedure, said Dr. Shireman, professor of health services research at Brown University in Providence, R.I.

However, the cost-effectiveness of thrombectomy began to kick in soon after. During the 90 days following index hospitalization, patients who underwent thrombectomy had substantial average reductions in their need for inpatient rehabilitation, time spent in skilled nursing facilities, and in outpatient rehabilitation. Overall, total medical costs during the first 90 days post discharge ran on average close to $5,000 less per patient following thrombectomy. In addition, based on their health status after 90 days, patients treated with thrombectomy were projected to have a greater than 1.7-year average life expectancy than those randomized to TPA only, with a projected net gain of 1.74 quality-adjusted life years (QALY) per patient and with a projected average decrease of roughly $23,000 in total lifetime medical costs.

Based on this average increase in QALYs and decreased long-term cost, adding thrombectomy to TPA for routine treatment of the types of patients enrolled in SWIFT-PRIME was economically dominant, Dr. Shireman said at the meeting sponsored by the American Heart Association. She also projected that despite the higher upfront cost for adding thrombectomy to treatment, the eventual savings in long-term care meant that thrombectomy began producing a net saving once patients survived for more than 22 months following their index hospitalization.

Dr. Campbell reported very similar findings in his analysis of data collected from the EXTEND-IA trial, which randomized 70 patients at 10 centers in Australia and New Zealand. During the first 90 days of treatment, including the index hospitalization, treatment with thrombectomy plus TPA saved an average of roughly $4,000 U.S.per patient, compared with TPA only, even though the average incremental cost for adding thrombectomy was nearly $11,000 U.S. The overall increased total 90-day costs with TPA only was largely driven by a substantially longer time spent hospitalized among the TPA-only patients, compared with those treated with thrombectomy plus TPA, said Dr. Campbell, a neurologist and head of hyperacute stroke at Royal Melbourne Hospital.

In addition, adding thrombectomy resulted in a projected average 4-year increase in life expectancy, and an average gain of about 3 QALYs per patient. Thrombectomy “is an incredibly powerful procedure, not just in terms of clinical response but also in terms of economics,” he concluded. Even when judged by the worst-case scenario of the analysis, “there is a 100% probability that the cost-effectiveness per QALY is less than $10,000 U.S., which is incredible value,” Dr. Campbell said.

SWIFT-PRIME was sponsored by Covidien/Medtronic. EXTEND-IA received partial funding through an unrestricted grant from Covidien/Medtronic. Dr. Shireman and Dr. Campbell had no personal disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

LOS ANGELES – Endovascular thrombectomy is not only clinically the best option for many patients with acute, ischemic strokes involving a proximal occlusion in a large cerebral artery; it’s also highly cost effective, based on follow-up analyses of two of the five randomized trials published in 2015 that collectively established thrombectomy as standard of care for these patients.

Thrombectomy plus administration of intravenous tissue plasminogen activator (TPA), compared with TPA only, “is highly cost effective and economically dominant with lower long-term cost and better outcomes,” Theresa I. Shireman, Ph.D., said at the International Stroke Conference.

And in an independent analysis of data from a totally different trial, endovascular thrombectomy on average reduced patients’ acute length of hospitalization, improved their survival and quality of life, and was cost saving when compared with treatment with intravenous TPA only, which had previously been the standard of care, Dr. Bruce C.V. Campbell reported at the meeting.

The analysis presented by Dr. Shireman used data collected in the SWIFT-PRIME trial, which randomized 196 patients at centers in the United States and Europe to treatment with either intravenous TPA plus endovascular thrombectomy or TPA alone. Average total costs during the index hospitalization ran to roughly $46,000 in the combined-treatment arm and about $29,000 in the TPA-only arm, a difference largely driven by a roughly $15,000 average incremental cost for the thrombectomy procedure, said Dr. Shireman, professor of health services research at Brown University in Providence, R.I.

However, the cost-effectiveness of thrombectomy began to kick in soon after. During the 90 days following index hospitalization, patients who underwent thrombectomy had substantial average reductions in their need for inpatient rehabilitation, time spent in skilled nursing facilities, and in outpatient rehabilitation. Overall, total medical costs during the first 90 days post discharge ran on average close to $5,000 less per patient following thrombectomy. In addition, based on their health status after 90 days, patients treated with thrombectomy were projected to have a greater than 1.7-year average life expectancy than those randomized to TPA only, with a projected net gain of 1.74 quality-adjusted life years (QALY) per patient and with a projected average decrease of roughly $23,000 in total lifetime medical costs.

Based on this average increase in QALYs and decreased long-term cost, adding thrombectomy to TPA for routine treatment of the types of patients enrolled in SWIFT-PRIME was economically dominant, Dr. Shireman said at the meeting sponsored by the American Heart Association. She also projected that despite the higher upfront cost for adding thrombectomy to treatment, the eventual savings in long-term care meant that thrombectomy began producing a net saving once patients survived for more than 22 months following their index hospitalization.

Dr. Campbell reported very similar findings in his analysis of data collected from the EXTEND-IA trial, which randomized 70 patients at 10 centers in Australia and New Zealand. During the first 90 days of treatment, including the index hospitalization, treatment with thrombectomy plus TPA saved an average of roughly $4,000 U.S.per patient, compared with TPA only, even though the average incremental cost for adding thrombectomy was nearly $11,000 U.S. The overall increased total 90-day costs with TPA only was largely driven by a substantially longer time spent hospitalized among the TPA-only patients, compared with those treated with thrombectomy plus TPA, said Dr. Campbell, a neurologist and head of hyperacute stroke at Royal Melbourne Hospital.

In addition, adding thrombectomy resulted in a projected average 4-year increase in life expectancy, and an average gain of about 3 QALYs per patient. Thrombectomy “is an incredibly powerful procedure, not just in terms of clinical response but also in terms of economics,” he concluded. Even when judged by the worst-case scenario of the analysis, “there is a 100% probability that the cost-effectiveness per QALY is less than $10,000 U.S., which is incredible value,” Dr. Campbell said.

SWIFT-PRIME was sponsored by Covidien/Medtronic. EXTEND-IA received partial funding through an unrestricted grant from Covidien/Medtronic. Dr. Shireman and Dr. Campbell had no personal disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

LOS ANGELES – For intraventricular hemorrhages of at least 20 mL, alteplase (Activase – Genentech) delivered directly into the clot by external ventricular drain almost doubles the odds of achieving a modified Rankin Score of 0-3 by 6 months.

More clot is removed – and patients with large intraventricular hemorrhages (IVHs) do better – with more vigorous alteplase dosing and when more than one drain is used.

The findings come from the Clot Lysis Evaluation of Accelerated Resolution (CLEAR III) trial, which randomized 249 IVH patients to 1 mg alteplase every 8 hours for up to 12 doses, and 251 to saline on the same schedule, delivered by external ventricular drain. The intervention didn’t make much difference with small hemorrhages.

In a video interview at the International Stroke Conference, investigator Dr. Issam Awad, a professor of surgery and neurology and director of neurovascular surgery at the University of Chicago, explained how to do the technique correctly for larger clots, and the expected benefits.

aotto@frontlinemedcom.com

LOS ANGELES – For intraventricular hemorrhages of at least 20 mL, alteplase (Activase – Genentech) delivered directly into the clot by external ventricular drain almost doubles the odds of achieving a modified Rankin Score of 0-3 by 6 months.

More clot is removed – and patients with large intraventricular hemorrhages (IVHs) do better – with more vigorous alteplase dosing and when more than one drain is used.

The findings come from the Clot Lysis Evaluation of Accelerated Resolution (CLEAR III) trial, which randomized 249 IVH patients to 1 mg alteplase every 8 hours for up to 12 doses, and 251 to saline on the same schedule, delivered by external ventricular drain. The intervention didn’t make much difference with small hemorrhages.

In a video interview at the International Stroke Conference, investigator Dr. Issam Awad, a professor of surgery and neurology and director of neurovascular surgery at the University of Chicago, explained how to do the technique correctly for larger clots, and the expected benefits.

aotto@frontlinemedcom.com

LOS ANGELES – For intraventricular hemorrhages of at least 20 mL, alteplase (Activase – Genentech) delivered directly into the clot by external ventricular drain almost doubles the odds of achieving a modified Rankin Score of 0-3 by 6 months.

More clot is removed – and patients with large intraventricular hemorrhages (IVHs) do better – with more vigorous alteplase dosing and when more than one drain is used.

The findings come from the Clot Lysis Evaluation of Accelerated Resolution (CLEAR III) trial, which randomized 249 IVH patients to 1 mg alteplase every 8 hours for up to 12 doses, and 251 to saline on the same schedule, delivered by external ventricular drain. The intervention didn’t make much difference with small hemorrhages.

In a video interview at the International Stroke Conference, investigator Dr. Issam Awad, a professor of surgery and neurology and director of neurovascular surgery at the University of Chicago, explained how to do the technique correctly for larger clots, and the expected benefits.

aotto@frontlinemedcom.com

WASHINGTON – Robotic angioplasty may deliver the same advantages when percutaneous coronary intervention is indicated for acute myocardial infarction as currently claimed for an elective PCI, according to results from a proof-of-principle study.

The first robotic PCI system, CorPath 200, was approved by the U.S. Food and Drug Administration in 2012, but the registration trial, called PRECISE (Percutaneous Robotically Enhanced Coronary Intervention), excluded patients with coronary thrombosis, according to a team of investigators at the Frederik Meijer Cardiovascular Institute, Grand Rapids, Mich. The current study focused exclusively on this population.

In “an initial experience” with robotic PCI in 17 acute MI patients led by Dr. Ryan D. Madder, an interventional cardiologist, “technical success” was achieved in 100% of patients with no repeat revascularizations in follow-up so far.

“These preliminary observations support the performance of larger studies to determine the role of robotic PCI in the treatment of acute MI,” said Andrew O’Brien, a medical student at Michigan State University, Ann Arbor, who presented the data at the meeting, sponsored by the Cardiovascular Research Institute at Washington Hospital Center.

The major proven advantage of robotic PCI is that it reduces radiation exposure to the operator, Mr. O’Brien said. While the procedure was performed in this study behind a lead-lined cockpit, it was noted that the operator works solely on the basis of imaging and could be anywhere, including at another facility. In addition, robotic PCI has at least a theoretical advantage of greater precision relative to conventional PCI.

In this study, technical success was defined as less than 30% residual stenosis after PCI in the absence of a PCI-associated death or the need for a repeat revascularization prior to hospital discharge. The median age of the 17 acute MI patients was 59 years with a range of about 10 years younger or older. Most (71%) were male. Radial arterial access was used in all cases.

Only 23% of the patients met criteria for relatively simple lesions (class A or B1). Just over half (53%) had class B2 lesions, which require at least two complicating characteristics, such as moderate tortuosity, irregular contour, or moderate to heavy calcification, and the remainder had class C lesions. In 10 cases (59%), an angiographic filling defect consistent with thrombus was present at the culprit lesion site.

In addition to achieving the goal reduction in residual stenosis without major adverse cardiovascular events in all patients, the investigators reported that procedural time, which averaged 69 minutes from the time of sheath insertion to removal of the guide catheter, was “acceptable.” The longest procedural time was under 100 minutes.

“We used the same criteria for evaluating outcomes as employed in the original PRECISE study,” Mr. O’Brien said. He explained that acute MI patients were excluded in the published PRECISE trial data because there was no protocol at that time for converting to a conventional procedure on an urgent basis in the case of unexpected problems. With more experience, there was greater confidence that urgent complications could be addressed.

In the multicenter PRECISE trial, which led to approval of the robotic system, 164 candidates for elective PCI were enrolled (J Am Coll Cardiol. 2013;61[15]:1596-1600). Technical success was 98.8%. Although there was no control arm, radiation exposure was reported to be 95% lower for operators participating in that study than levels found at the traditional table position.

Data from the current study provide preliminary evidence that robotic PCI is feasible for management of acute MI. While confirmatory studies are needed for this indication, the Michigan investigators also advocated more studies to evaluate whether robotic PCI improves outcome. They cited the potential for more precise placement of stents to reduce the risk of complications.

“Robotic PCI is still not very widely performed,” said coinvestigator Andrew LaCombe, who suggested that its potential advantages deserve broader evaluation.

Dr. Madder disclosed a financial relationship with InfraRedx.

WASHINGTON – Robotic angioplasty may deliver the same advantages when percutaneous coronary intervention is indicated for acute myocardial infarction as currently claimed for an elective PCI, according to results from a proof-of-principle study.

The first robotic PCI system, CorPath 200, was approved by the U.S. Food and Drug Administration in 2012, but the registration trial, called PRECISE (Percutaneous Robotically Enhanced Coronary Intervention), excluded patients with coronary thrombosis, according to a team of investigators at the Frederik Meijer Cardiovascular Institute, Grand Rapids, Mich. The current study focused exclusively on this population.

In “an initial experience” with robotic PCI in 17 acute MI patients led by Dr. Ryan D. Madder, an interventional cardiologist, “technical success” was achieved in 100% of patients with no repeat revascularizations in follow-up so far.

“These preliminary observations support the performance of larger studies to determine the role of robotic PCI in the treatment of acute MI,” said Andrew O’Brien, a medical student at Michigan State University, Ann Arbor, who presented the data at the meeting, sponsored by the Cardiovascular Research Institute at Washington Hospital Center.

The major proven advantage of robotic PCI is that it reduces radiation exposure to the operator, Mr. O’Brien said. While the procedure was performed in this study behind a lead-lined cockpit, it was noted that the operator works solely on the basis of imaging and could be anywhere, including at another facility. In addition, robotic PCI has at least a theoretical advantage of greater precision relative to conventional PCI.

In this study, technical success was defined as less than 30% residual stenosis after PCI in the absence of a PCI-associated death or the need for a repeat revascularization prior to hospital discharge. The median age of the 17 acute MI patients was 59 years with a range of about 10 years younger or older. Most (71%) were male. Radial arterial access was used in all cases.

Only 23% of the patients met criteria for relatively simple lesions (class A or B1). Just over half (53%) had class B2 lesions, which require at least two complicating characteristics, such as moderate tortuosity, irregular contour, or moderate to heavy calcification, and the remainder had class C lesions. In 10 cases (59%), an angiographic filling defect consistent with thrombus was present at the culprit lesion site.

In addition to achieving the goal reduction in residual stenosis without major adverse cardiovascular events in all patients, the investigators reported that procedural time, which averaged 69 minutes from the time of sheath insertion to removal of the guide catheter, was “acceptable.” The longest procedural time was under 100 minutes.

“We used the same criteria for evaluating outcomes as employed in the original PRECISE study,” Mr. O’Brien said. He explained that acute MI patients were excluded in the published PRECISE trial data because there was no protocol at that time for converting to a conventional procedure on an urgent basis in the case of unexpected problems. With more experience, there was greater confidence that urgent complications could be addressed.

In the multicenter PRECISE trial, which led to approval of the robotic system, 164 candidates for elective PCI were enrolled (J Am Coll Cardiol. 2013;61[15]:1596-1600). Technical success was 98.8%. Although there was no control arm, radiation exposure was reported to be 95% lower for operators participating in that study than levels found at the traditional table position.

Data from the current study provide preliminary evidence that robotic PCI is feasible for management of acute MI. While confirmatory studies are needed for this indication, the Michigan investigators also advocated more studies to evaluate whether robotic PCI improves outcome. They cited the potential for more precise placement of stents to reduce the risk of complications.

“Robotic PCI is still not very widely performed,” said coinvestigator Andrew LaCombe, who suggested that its potential advantages deserve broader evaluation.

Dr. Madder disclosed a financial relationship with InfraRedx.

WASHINGTON – Robotic angioplasty may deliver the same advantages when percutaneous coronary intervention is indicated for acute myocardial infarction as currently claimed for an elective PCI, according to results from a proof-of-principle study.

The first robotic PCI system, CorPath 200, was approved by the U.S. Food and Drug Administration in 2012, but the registration trial, called PRECISE (Percutaneous Robotically Enhanced Coronary Intervention), excluded patients with coronary thrombosis, according to a team of investigators at the Frederik Meijer Cardiovascular Institute, Grand Rapids, Mich. The current study focused exclusively on this population.

In “an initial experience” with robotic PCI in 17 acute MI patients led by Dr. Ryan D. Madder, an interventional cardiologist, “technical success” was achieved in 100% of patients with no repeat revascularizations in follow-up so far.

“These preliminary observations support the performance of larger studies to determine the role of robotic PCI in the treatment of acute MI,” said Andrew O’Brien, a medical student at Michigan State University, Ann Arbor, who presented the data at the meeting, sponsored by the Cardiovascular Research Institute at Washington Hospital Center.

The major proven advantage of robotic PCI is that it reduces radiation exposure to the operator, Mr. O’Brien said. While the procedure was performed in this study behind a lead-lined cockpit, it was noted that the operator works solely on the basis of imaging and could be anywhere, including at another facility. In addition, robotic PCI has at least a theoretical advantage of greater precision relative to conventional PCI.

In this study, technical success was defined as less than 30% residual stenosis after PCI in the absence of a PCI-associated death or the need for a repeat revascularization prior to hospital discharge. The median age of the 17 acute MI patients was 59 years with a range of about 10 years younger or older. Most (71%) were male. Radial arterial access was used in all cases.

Only 23% of the patients met criteria for relatively simple lesions (class A or B1). Just over half (53%) had class B2 lesions, which require at least two complicating characteristics, such as moderate tortuosity, irregular contour, or moderate to heavy calcification, and the remainder had class C lesions. In 10 cases (59%), an angiographic filling defect consistent with thrombus was present at the culprit lesion site.

In addition to achieving the goal reduction in residual stenosis without major adverse cardiovascular events in all patients, the investigators reported that procedural time, which averaged 69 minutes from the time of sheath insertion to removal of the guide catheter, was “acceptable.” The longest procedural time was under 100 minutes.

“We used the same criteria for evaluating outcomes as employed in the original PRECISE study,” Mr. O’Brien said. He explained that acute MI patients were excluded in the published PRECISE trial data because there was no protocol at that time for converting to a conventional procedure on an urgent basis in the case of unexpected problems. With more experience, there was greater confidence that urgent complications could be addressed.

In the multicenter PRECISE trial, which led to approval of the robotic system, 164 candidates for elective PCI were enrolled (J Am Coll Cardiol. 2013;61[15]:1596-1600). Technical success was 98.8%. Although there was no control arm, radiation exposure was reported to be 95% lower for operators participating in that study than levels found at the traditional table position.

Data from the current study provide preliminary evidence that robotic PCI is feasible for management of acute MI. While confirmatory studies are needed for this indication, the Michigan investigators also advocated more studies to evaluate whether robotic PCI improves outcome. They cited the potential for more precise placement of stents to reduce the risk of complications.

“Robotic PCI is still not very widely performed,” said coinvestigator Andrew LaCombe, who suggested that its potential advantages deserve broader evaluation.

Dr. Madder disclosed a financial relationship with InfraRedx.

LOS ANGELES – Clot removal to recanalize the occluded intracerebral arteries of acute ischemic stroke patients was as effective for producing good outcomes in patients aged 80 years or older as it was in younger patients, according to results from a pooled analysis of 1,287 patients in five separate but similar randomized trials.

This unprecedented evidence for the safety and efficacy of thrombectomy (also known as embolectomy) in octogenarians experiencing an acute occlusive, large-vessel, proximal anterior-circulation stroke was one of several new findings from the pooled analysis that should help further push thrombectomy to the forefront of acute care for patients undergoing this type of ischemic stroke, predicted Dr. Wade S. Smith in a video interview at the International Stroke Conference.

“By looking at all the data, we have much more refined information on the robustness of the treatment across age groups, which is quite important, especially patients in the 80-plus age group,” commented Dr. Smith, professor of neurology and chief of the neurovascular division at the University of California, San Francisco.

Until now, during the year following the reports in early 2015 from all five studies, “age had been a limiting factor” in applying the practicing-changing intervention of thrombectomy to patients, he noted.

“This [the new pooled analysis] will change that,” Dr. Smith predicted. “It does not apply to patients who were infirm prior to their stroke – but for patients who were otherwise healthy, with a modified Rankin scale level of 0 or 1 at initial presentation, it appears that they benefit [from thrombectomy] regardless of their age.” In the pooled analysis, 198 of the 1,287 total patients (15%) were at least 80 years old.

“It removes age discrimination. A healthy 80-year-old may do extremely well with this treatment,” Dr. Smith said.

The consistency of benefit across a wide range of stroke severity that showed up in the trials as four distinct strata of NIH Stroke Scale scores prior to treatment was another important finding that could not previously be definitively made by analyzing each of the five trials individually.

In patients with stroke-severity scores that ranged from 10 or less (the least severely affected) to patients with scores of 21 or greater, all had post-thrombectomy improvements that clustered around the overall average number-needed-to-treat of 2.6 patients to reduce the disability of one patient at follow-up by at least one level on the modified Rankin scale.

Other notable findings from the pooled analysis were that thrombectomy also produced a consistent benefit to patients across every other subgroup examined, including sex, specific occlusion site, whether or not patients also received thrombolytic treatment with tissue plasminogen activator, and time to thrombectomy treatment (5 or fewer hours from stroke onset or more than 5 hours), reported Dr. Michael D. Hill and Dr. Tudor G. Jovin in a joint presentation at the meeting, sponsored by the American Heart Association.

Their pooled analysis, known as HERMES, pooled data from the MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA trials, all run during 2010-2014.

“Endovascular treatment is a highly effective treatment across all subgroups,” concluded Dr. Hill and Dr. Jovin as they completed their talk. “These data may provide additional support for endovascular treatment in subgroups not addressed in the individual trials.”

Concurrent with their report at the meeting, the results appeared in a paper published online (Lancet. 2016 Feb 18;doi: 10.1016/S0140-6736(16)00163-X).

Both Dr. Jovin and Dr. Hill shared the enthusiasm of Dr. Smith and others in the packed meeting room about the age finding.

“Older patients seemed to benefit even more” from thrombectomy, compared with younger patients, noted Dr. Jovin, chief of the stroke division at the University of Pittsburgh and a coinvestigator on SWIFT PRIME. “There is no reason to deny this treatment to appropriately selected patients based on age,” he said.

“There is no upper age limit,” agreed Dr. Hill, professor of neurology and director of the stroke unit at the University of Calgary (Alta.) and a coinvestigator on the ESCAPE trial. “If it’s an otherwise healthy 90-year-old who is living independently, you can surely consider them for this treatment.”

HERMES received fundings through an unrestricted grant from Medtronic. Dr. Hill and Dr. Jovin had no personal disclosures. Dr. Smith served on the data safety and monitoring board for a trial funded by Stryker.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

LOS ANGELES – Clot removal to recanalize the occluded intracerebral arteries of acute ischemic stroke patients was as effective for producing good outcomes in patients aged 80 years or older as it was in younger patients, according to results from a pooled analysis of 1,287 patients in five separate but similar randomized trials.

This unprecedented evidence for the safety and efficacy of thrombectomy (also known as embolectomy) in octogenarians experiencing an acute occlusive, large-vessel, proximal anterior-circulation stroke was one of several new findings from the pooled analysis that should help further push thrombectomy to the forefront of acute care for patients undergoing this type of ischemic stroke, predicted Dr. Wade S. Smith in a video interview at the International Stroke Conference.

“By looking at all the data, we have much more refined information on the robustness of the treatment across age groups, which is quite important, especially patients in the 80-plus age group,” commented Dr. Smith, professor of neurology and chief of the neurovascular division at the University of California, San Francisco.

Until now, during the year following the reports in early 2015 from all five studies, “age had been a limiting factor” in applying the practicing-changing intervention of thrombectomy to patients, he noted.

“This [the new pooled analysis] will change that,” Dr. Smith predicted. “It does not apply to patients who were infirm prior to their stroke – but for patients who were otherwise healthy, with a modified Rankin scale level of 0 or 1 at initial presentation, it appears that they benefit [from thrombectomy] regardless of their age.” In the pooled analysis, 198 of the 1,287 total patients (15%) were at least 80 years old.

“It removes age discrimination. A healthy 80-year-old may do extremely well with this treatment,” Dr. Smith said.

The consistency of benefit across a wide range of stroke severity that showed up in the trials as four distinct strata of NIH Stroke Scale scores prior to treatment was another important finding that could not previously be definitively made by analyzing each of the five trials individually.

In patients with stroke-severity scores that ranged from 10 or less (the least severely affected) to patients with scores of 21 or greater, all had post-thrombectomy improvements that clustered around the overall average number-needed-to-treat of 2.6 patients to reduce the disability of one patient at follow-up by at least one level on the modified Rankin scale.

Other notable findings from the pooled analysis were that thrombectomy also produced a consistent benefit to patients across every other subgroup examined, including sex, specific occlusion site, whether or not patients also received thrombolytic treatment with tissue plasminogen activator, and time to thrombectomy treatment (5 or fewer hours from stroke onset or more than 5 hours), reported Dr. Michael D. Hill and Dr. Tudor G. Jovin in a joint presentation at the meeting, sponsored by the American Heart Association.

Their pooled analysis, known as HERMES, pooled data from the MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA trials, all run during 2010-2014.

“Endovascular treatment is a highly effective treatment across all subgroups,” concluded Dr. Hill and Dr. Jovin as they completed their talk. “These data may provide additional support for endovascular treatment in subgroups not addressed in the individual trials.”

Concurrent with their report at the meeting, the results appeared in a paper published online (Lancet. 2016 Feb 18;doi: 10.1016/S0140-6736(16)00163-X).

Both Dr. Jovin and Dr. Hill shared the enthusiasm of Dr. Smith and others in the packed meeting room about the age finding.

“Older patients seemed to benefit even more” from thrombectomy, compared with younger patients, noted Dr. Jovin, chief of the stroke division at the University of Pittsburgh and a coinvestigator on SWIFT PRIME. “There is no reason to deny this treatment to appropriately selected patients based on age,” he said.

“There is no upper age limit,” agreed Dr. Hill, professor of neurology and director of the stroke unit at the University of Calgary (Alta.) and a coinvestigator on the ESCAPE trial. “If it’s an otherwise healthy 90-year-old who is living independently, you can surely consider them for this treatment.”

HERMES received fundings through an unrestricted grant from Medtronic. Dr. Hill and Dr. Jovin had no personal disclosures. Dr. Smith served on the data safety and monitoring board for a trial funded by Stryker.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

LOS ANGELES – Clot removal to recanalize the occluded intracerebral arteries of acute ischemic stroke patients was as effective for producing good outcomes in patients aged 80 years or older as it was in younger patients, according to results from a pooled analysis of 1,287 patients in five separate but similar randomized trials.

This unprecedented evidence for the safety and efficacy of thrombectomy (also known as embolectomy) in octogenarians experiencing an acute occlusive, large-vessel, proximal anterior-circulation stroke was one of several new findings from the pooled analysis that should help further push thrombectomy to the forefront of acute care for patients undergoing this type of ischemic stroke, predicted Dr. Wade S. Smith in a video interview at the International Stroke Conference.

“By looking at all the data, we have much more refined information on the robustness of the treatment across age groups, which is quite important, especially patients in the 80-plus age group,” commented Dr. Smith, professor of neurology and chief of the neurovascular division at the University of California, San Francisco.

Until now, during the year following the reports in early 2015 from all five studies, “age had been a limiting factor” in applying the practicing-changing intervention of thrombectomy to patients, he noted.

“This [the new pooled analysis] will change that,” Dr. Smith predicted. “It does not apply to patients who were infirm prior to their stroke – but for patients who were otherwise healthy, with a modified Rankin scale level of 0 or 1 at initial presentation, it appears that they benefit [from thrombectomy] regardless of their age.” In the pooled analysis, 198 of the 1,287 total patients (15%) were at least 80 years old.

“It removes age discrimination. A healthy 80-year-old may do extremely well with this treatment,” Dr. Smith said.

The consistency of benefit across a wide range of stroke severity that showed up in the trials as four distinct strata of NIH Stroke Scale scores prior to treatment was another important finding that could not previously be definitively made by analyzing each of the five trials individually.

In patients with stroke-severity scores that ranged from 10 or less (the least severely affected) to patients with scores of 21 or greater, all had post-thrombectomy improvements that clustered around the overall average number-needed-to-treat of 2.6 patients to reduce the disability of one patient at follow-up by at least one level on the modified Rankin scale.

Other notable findings from the pooled analysis were that thrombectomy also produced a consistent benefit to patients across every other subgroup examined, including sex, specific occlusion site, whether or not patients also received thrombolytic treatment with tissue plasminogen activator, and time to thrombectomy treatment (5 or fewer hours from stroke onset or more than 5 hours), reported Dr. Michael D. Hill and Dr. Tudor G. Jovin in a joint presentation at the meeting, sponsored by the American Heart Association.

Their pooled analysis, known as HERMES, pooled data from the MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA trials, all run during 2010-2014.

“Endovascular treatment is a highly effective treatment across all subgroups,” concluded Dr. Hill and Dr. Jovin as they completed their talk. “These data may provide additional support for endovascular treatment in subgroups not addressed in the individual trials.”

Concurrent with their report at the meeting, the results appeared in a paper published online (Lancet. 2016 Feb 18;doi: 10.1016/S0140-6736(16)00163-X).

Both Dr. Jovin and Dr. Hill shared the enthusiasm of Dr. Smith and others in the packed meeting room about the age finding.

“Older patients seemed to benefit even more” from thrombectomy, compared with younger patients, noted Dr. Jovin, chief of the stroke division at the University of Pittsburgh and a coinvestigator on SWIFT PRIME. “There is no reason to deny this treatment to appropriately selected patients based on age,” he said.

“There is no upper age limit,” agreed Dr. Hill, professor of neurology and director of the stroke unit at the University of Calgary (Alta.) and a coinvestigator on the ESCAPE trial. “If it’s an otherwise healthy 90-year-old who is living independently, you can surely consider them for this treatment.”

HERMES received fundings through an unrestricted grant from Medtronic. Dr. Hill and Dr. Jovin had no personal disclosures. Dr. Smith served on the data safety and monitoring board for a trial funded by Stryker.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

LOS ANGELES – Nondiabetic, insulin-resistant patients who started pioglitazone within 6 months of an ischemic stroke or transient ischemic attack had almost a 3% absolute risk reduction in secondary strokes and myocardial infarctions after 5 years, in a randomized, clinical trial published online Feb. 17 in the New England Journal of Medicine.

Stroke or MI – the study’s primary combined outcome – occurred in 175 of 1,939 (9.0%) pioglitazone (Actos) patients, but 228 of 1,937 (11.8%) placebo patients (hazard ratio, 0.76; P = 0.007). There was no significant difference in all-cause mortality (HR, 0.93; P = 0.52).

Seventy-three pioglitazone patients (3.8%) developed diabetes, compared with 149 (7.7%) in the placebo group (HR, 0.48; P less than 0.001). That wasn’t a surprise; pioglitazone has been shown to protect insulin resistant patients against diabetes, the study investigators noted (N Engl J Med. 2016 Feb 17; doi: 10.1056/NEJMoa1506930).

Known side effects showed up as well. Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg (52.2% versus 33.7%, P less than 0.001), edema (35.6% versus 24.9%, P less than 0.001), and bone fracture requiring surgery or hospitalization (5.1% versus 3.2%, P = 0.003).

Heart failure – another known risk with the drug – did not show up in the trial; people with heart failure histories or other risk factors were excluded.

The median baseline modified Rankin Scale in both groups was 1, and the median NIH Stroke Scale score was 0. The pioglitazone target dose was 45 mg daily.

Insulin resistance is a risk factor for heart attack and stroke, which may help explain the thiazolidinedione’s apparent protective effects. It was defined in the trial as a score greater than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index.

So, should pioglitazone be a part of routine post-stroke care?

In a video interview at the International Stroke Conference, lead investigator Dr. Walter N. Kernan, a professor of general medicine at Yale University, New Haven, Conn., shared his thoughts.

aotto@frontlinemedcom.com

LOS ANGELES – Nondiabetic, insulin-resistant patients who started pioglitazone within 6 months of an ischemic stroke or transient ischemic attack had almost a 3% absolute risk reduction in secondary strokes and myocardial infarctions after 5 years, in a randomized, clinical trial published online Feb. 17 in the New England Journal of Medicine.

Stroke or MI – the study’s primary combined outcome – occurred in 175 of 1,939 (9.0%) pioglitazone (Actos) patients, but 228 of 1,937 (11.8%) placebo patients (hazard ratio, 0.76; P = 0.007). There was no significant difference in all-cause mortality (HR, 0.93; P = 0.52).

Seventy-three pioglitazone patients (3.8%) developed diabetes, compared with 149 (7.7%) in the placebo group (HR, 0.48; P less than 0.001). That wasn’t a surprise; pioglitazone has been shown to protect insulin resistant patients against diabetes, the study investigators noted (N Engl J Med. 2016 Feb 17; doi: 10.1056/NEJMoa1506930).

Known side effects showed up as well. Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg (52.2% versus 33.7%, P less than 0.001), edema (35.6% versus 24.9%, P less than 0.001), and bone fracture requiring surgery or hospitalization (5.1% versus 3.2%, P = 0.003).

Heart failure – another known risk with the drug – did not show up in the trial; people with heart failure histories or other risk factors were excluded.

The median baseline modified Rankin Scale in both groups was 1, and the median NIH Stroke Scale score was 0. The pioglitazone target dose was 45 mg daily.

Insulin resistance is a risk factor for heart attack and stroke, which may help explain the thiazolidinedione’s apparent protective effects. It was defined in the trial as a score greater than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index.

So, should pioglitazone be a part of routine post-stroke care?

In a video interview at the International Stroke Conference, lead investigator Dr. Walter N. Kernan, a professor of general medicine at Yale University, New Haven, Conn., shared his thoughts.

aotto@frontlinemedcom.com

LOS ANGELES – Nondiabetic, insulin-resistant patients who started pioglitazone within 6 months of an ischemic stroke or transient ischemic attack had almost a 3% absolute risk reduction in secondary strokes and myocardial infarctions after 5 years, in a randomized, clinical trial published online Feb. 17 in the New England Journal of Medicine.

Stroke or MI – the study’s primary combined outcome – occurred in 175 of 1,939 (9.0%) pioglitazone (Actos) patients, but 228 of 1,937 (11.8%) placebo patients (hazard ratio, 0.76; P = 0.007). There was no significant difference in all-cause mortality (HR, 0.93; P = 0.52).

Seventy-three pioglitazone patients (3.8%) developed diabetes, compared with 149 (7.7%) in the placebo group (HR, 0.48; P less than 0.001). That wasn’t a surprise; pioglitazone has been shown to protect insulin resistant patients against diabetes, the study investigators noted (N Engl J Med. 2016 Feb 17; doi: 10.1056/NEJMoa1506930).

Known side effects showed up as well. Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg (52.2% versus 33.7%, P less than 0.001), edema (35.6% versus 24.9%, P less than 0.001), and bone fracture requiring surgery or hospitalization (5.1% versus 3.2%, P = 0.003).

Heart failure – another known risk with the drug – did not show up in the trial; people with heart failure histories or other risk factors were excluded.

The median baseline modified Rankin Scale in both groups was 1, and the median NIH Stroke Scale score was 0. The pioglitazone target dose was 45 mg daily.

Insulin resistance is a risk factor for heart attack and stroke, which may help explain the thiazolidinedione’s apparent protective effects. It was defined in the trial as a score greater than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index.

So, should pioglitazone be a part of routine post-stroke care?

In a video interview at the International Stroke Conference, lead investigator Dr. Walter N. Kernan, a professor of general medicine at Yale University, New Haven, Conn., shared his thoughts.

aotto@frontlinemedcom.com

PHOENIX – Cardiothoracic surgeons who implant left ventricular assist devices in patients with failing hearts remain at a loss to fully explain why they started seeing a sharp increase in thrombus clogging in these devices in 2012, but nevertheless they are gaining a better sense of how to minimize the risk.

Three key principles for minimizing thrombosis risk are selecting the right patients to receive left ventricular assist devices (LVAD), applying optimal management strategies once patients receive a LVAD, and maintaining adequate flow of blood through the pump, Dr. Francis D. Pagani said in a talk at a session devoted to pump thrombosis at the annual meeting of the Society of Thoracic Surgeons.

Mitchel L. Zoler/Frontline Medical News

Other critical aspects include optimal implantation technique, quick work-up of patients to rule out reversible LVAD inflow or outflow problems once pump thrombosis is suspected, and ceasing medical therapy of the thrombosis if it proves ineffective and instead progress to surgical pump exchange, pump explantation, or heart transplant when necessary, said Dr. Ahmet Kilic, a cardiothoracic surgeon at the Ohio State University, Columbus.

Another key issue is that, now that the pump thrombosis incidence is averaging about 10% of LVAD recipients, with an incidence rate during 2-year follow-up as high as 24% reported from one series, surgeons and physicians who care for LVAD patients must have a high index of suspicion and routinely screen LVAD recipients for early signs of pump thrombosis. The best way to catch pump thrombosis early seems to be by regularly measuring patients’ serum level of lactate dehydrogenase (LDH), said Dr. Robert L. Kormos, professor of surgery and director of the artificial heart program at the University of Pittsburgh.

Mitchel L. Zoler/Frontline Medical News

“We measure LDH on most clinic visits, whether or not the patient has an indication of pump thrombosis. We need to screen [LDH levels] much more routinely than we used to,” he said during the session. “Elevated LDH is probably the first and most reliable early sign, but you need to also assess LDH isoenzymes because we’ve had patients with an elevation but no sign of pump thrombosis, and their isoenzymes showed that the increased LDH was coming from their liver,” Dr. Kormos said in an interview.

Although serial measurements and isoenzyme analysis can establish a sharp rise in heart-specific LDH in an individual patient, a report at the meeting documented that in a series of 53 patients with pump thrombosis treated at either of two U.S. centers, an LDH level of at least 1,155 IU/L flagged pump thrombosis with a fairly high sensitivity and specificity. This LDH level is roughly five times the upper limit of normal, noted Dr. Pagani, professor of surgery and surgical director of adult heart transplantation at the University of Michigan, Ann Arbor, and a senior author on this report.

But prior to this report Dr. Kormos said that he regarded a LDH level of 600-800 IU/L as enough of an elevation above normal to prompt concern and investigation. And he criticized some LVAD programs that allow LDH levels to rise much higher.

“I know of clinicians who see a LDH of 1,500-2,000 IU/L but the patient seems okay and they wonder if they should change out the pump. For me, it’s a no brainer. Others try to list a patient like this for a heart transplant so they can avoid doing a pump exchange. I think that’s dangerous; it risks liver failure or renal failure. I would not sit on any LVAD that is starting to produce signs of hemolysis syndrome, but some places do this,” Dr. Kormos said in an interview.

“Pump thrombosis probably did not get addressed in as timely a fashion as it should have been” when it was first seen on the rise in 2012, noted Dr. James K. Kirklin, professor of surgery and director of cardiothoracic surgery at the University of Alabama, Birmingham. “It is now being addressed, and we realize that this is not just a pump problem but also involves patient factors and management factors that we need to learn more about. We are quite ignorant of the patient factors and understanding their contributions to bleeding and thrombosis,” said Dr. Kirklin. He also acknowledged that whatever role the current generation of LVAD pumps play in causing thrombosis will not quickly resolve.

“I’m looking forward to a new generation of pumps, but the pumps we have today will probably remain for another 3-5 years.”

The issue of LVAD pump thrombosis first came into clear focus with publication at the start of 2014 of a report that tracked its incidence from 2004 to mid-2013 at three U.S. centers that had placed a total of 895 LVADs in 837 patients. The annual rate of new episodes of pump thrombosis jumped from about 1%-2% of LVAD recipients throughout the first part of the study period through the end of 2011, to an annual rate of about 10% by mid 2013 (N Engl J Med. 2014 Jan 2;370[1]:33-40).

“The inflection occurred in about 2012,” noted Dr. Nicholas G. Smedira, a cardiothoracic surgeon at the Cleveland Clinic. “No one has figured out why” the incidence suddenly spiked starting in 2012 and intensified in 2013, he said. This epidemic of pump thrombosis has produced “devastating complications” that have led to multiple readmissions and reduced cost-effectiveness of LVADs and has affected how the heart transplant community allocates hearts, Dr. Smedira said during his talk at the session. He noted that once the surge in pump thrombosis started, the timing of the appearance of significant thrombus shifted earlier, often occurring within 2-3 months after LVAD placement. There now is “increasing device-related pessimism” and increasing demoralization among clinicians because of this recurring complication, he said.

Mitchel L. Zoler/Frontline Medical News

More recent data show the trend toward increasingly higher rates of pump thrombosis continuing through the end of 2013, with the situation during 2014 a bit less clear. Late last year, data from 9,808 U.S. patients who received an LVAD and entered the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) showed that the incidence of pump thrombosis during the first 6 months following an implant rose from 1% in 2008 to 2% in 2009 and in 2010, 4% in 2011, 7% in 2012, 8% in 2013, and then eased back to 5% in the first half of 2014 (J Heart Lung Transplant. 2015 Dec;34[12]:1515-26). The annual rate rose from 2% in 2008 to a peak of 11% in 2013, with 12-month data from 2014 not yet available at the time of this report.

“The modest reduction of observed pump thrombosis at 6 months during 2014 has occurred in a milieu of heightened intensity of anti-coagulation management, greater surgical awareness of optimal pump implantation and positioning and pump speed management. Thus, one may speculate that current thrombosis risk-mitigation strategies have contributed to reducing but not eliminating the increased thrombosis risk observed since 2011,” concluded the authors of the report.

Surgeons and cardiologists must now have a high index of suspicion for pump thrombosis in LVAD recipients, and be especially on the lookout for four key flags of a problem, said Dr. Kormos. The first is a rising LDH level, but additional flags include an isolated power elevation that doesn’t correlate with anything else, evidence of hemolysis, and new-onset heart failure symptoms. These can occur individually or in some combination. He recommended following a diagnostic algorithm first presented in 2013 that remains very valid today (J Heart Lung Transplant. 2013 July;32[7]:667-70).

Dr. Kormos also highlighted that the presentation of pump thrombosis can differ between the two LVADs most commonly used in U.S. practice, the HeartMate II and the HeartWare devices. A LDH elevation is primarily an indicator for HeartMate II, while both that model and the HeartWare device show sustained, isolated power elevations when thrombosis occurs.

Dr. Pagani, Dr. Kirklin, and Dr. Smedira had no disclosures. Dr. Kormos has received travel support from HeartWare. Dr. Kilic has been a consultant to Thoratec and a speaker on behalf of Baxter International.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

PHOENIX – Cardiothoracic surgeons who implant left ventricular assist devices in patients with failing hearts remain at a loss to fully explain why they started seeing a sharp increase in thrombus clogging in these devices in 2012, but nevertheless they are gaining a better sense of how to minimize the risk.

Three key principles for minimizing thrombosis risk are selecting the right patients to receive left ventricular assist devices (LVAD), applying optimal management strategies once patients receive a LVAD, and maintaining adequate flow of blood through the pump, Dr. Francis D. Pagani said in a talk at a session devoted to pump thrombosis at the annual meeting of the Society of Thoracic Surgeons.

Mitchel L. Zoler/Frontline Medical News

Other critical aspects include optimal implantation technique, quick work-up of patients to rule out reversible LVAD inflow or outflow problems once pump thrombosis is suspected, and ceasing medical therapy of the thrombosis if it proves ineffective and instead progress to surgical pump exchange, pump explantation, or heart transplant when necessary, said Dr. Ahmet Kilic, a cardiothoracic surgeon at the Ohio State University, Columbus.

Another key issue is that, now that the pump thrombosis incidence is averaging about 10% of LVAD recipients, with an incidence rate during 2-year follow-up as high as 24% reported from one series, surgeons and physicians who care for LVAD patients must have a high index of suspicion and routinely screen LVAD recipients for early signs of pump thrombosis. The best way to catch pump thrombosis early seems to be by regularly measuring patients’ serum level of lactate dehydrogenase (LDH), said Dr. Robert L. Kormos, professor of surgery and director of the artificial heart program at the University of Pittsburgh.

Mitchel L. Zoler/Frontline Medical News

“We measure LDH on most clinic visits, whether or not the patient has an indication of pump thrombosis. We need to screen [LDH levels] much more routinely than we used to,” he said during the session. “Elevated LDH is probably the first and most reliable early sign, but you need to also assess LDH isoenzymes because we’ve had patients with an elevation but no sign of pump thrombosis, and their isoenzymes showed that the increased LDH was coming from their liver,” Dr. Kormos said in an interview.

Although serial measurements and isoenzyme analysis can establish a sharp rise in heart-specific LDH in an individual patient, a report at the meeting documented that in a series of 53 patients with pump thrombosis treated at either of two U.S. centers, an LDH level of at least 1,155 IU/L flagged pump thrombosis with a fairly high sensitivity and specificity. This LDH level is roughly five times the upper limit of normal, noted Dr. Pagani, professor of surgery and surgical director of adult heart transplantation at the University of Michigan, Ann Arbor, and a senior author on this report.

But prior to this report Dr. Kormos said that he regarded a LDH level of 600-800 IU/L as enough of an elevation above normal to prompt concern and investigation. And he criticized some LVAD programs that allow LDH levels to rise much higher.

“I know of clinicians who see a LDH of 1,500-2,000 IU/L but the patient seems okay and they wonder if they should change out the pump. For me, it’s a no brainer. Others try to list a patient like this for a heart transplant so they can avoid doing a pump exchange. I think that’s dangerous; it risks liver failure or renal failure. I would not sit on any LVAD that is starting to produce signs of hemolysis syndrome, but some places do this,” Dr. Kormos said in an interview.

“Pump thrombosis probably did not get addressed in as timely a fashion as it should have been” when it was first seen on the rise in 2012, noted Dr. James K. Kirklin, professor of surgery and director of cardiothoracic surgery at the University of Alabama, Birmingham. “It is now being addressed, and we realize that this is not just a pump problem but also involves patient factors and management factors that we need to learn more about. We are quite ignorant of the patient factors and understanding their contributions to bleeding and thrombosis,” said Dr. Kirklin. He also acknowledged that whatever role the current generation of LVAD pumps play in causing thrombosis will not quickly resolve.

“I’m looking forward to a new generation of pumps, but the pumps we have today will probably remain for another 3-5 years.”

The issue of LVAD pump thrombosis first came into clear focus with publication at the start of 2014 of a report that tracked its incidence from 2004 to mid-2013 at three U.S. centers that had placed a total of 895 LVADs in 837 patients. The annual rate of new episodes of pump thrombosis jumped from about 1%-2% of LVAD recipients throughout the first part of the study period through the end of 2011, to an annual rate of about 10% by mid 2013 (N Engl J Med. 2014 Jan 2;370[1]:33-40).

“The inflection occurred in about 2012,” noted Dr. Nicholas G. Smedira, a cardiothoracic surgeon at the Cleveland Clinic. “No one has figured out why” the incidence suddenly spiked starting in 2012 and intensified in 2013, he said. This epidemic of pump thrombosis has produced “devastating complications” that have led to multiple readmissions and reduced cost-effectiveness of LVADs and has affected how the heart transplant community allocates hearts, Dr. Smedira said during his talk at the session. He noted that once the surge in pump thrombosis started, the timing of the appearance of significant thrombus shifted earlier, often occurring within 2-3 months after LVAD placement. There now is “increasing device-related pessimism” and increasing demoralization among clinicians because of this recurring complication, he said.

Mitchel L. Zoler/Frontline Medical News

More recent data show the trend toward increasingly higher rates of pump thrombosis continuing through the end of 2013, with the situation during 2014 a bit less clear. Late last year, data from 9,808 U.S. patients who received an LVAD and entered the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) showed that the incidence of pump thrombosis during the first 6 months following an implant rose from 1% in 2008 to 2% in 2009 and in 2010, 4% in 2011, 7% in 2012, 8% in 2013, and then eased back to 5% in the first half of 2014 (J Heart Lung Transplant. 2015 Dec;34[12]:1515-26). The annual rate rose from 2% in 2008 to a peak of 11% in 2013, with 12-month data from 2014 not yet available at the time of this report.

“The modest reduction of observed pump thrombosis at 6 months during 2014 has occurred in a milieu of heightened intensity of anti-coagulation management, greater surgical awareness of optimal pump implantation and positioning and pump speed management. Thus, one may speculate that current thrombosis risk-mitigation strategies have contributed to reducing but not eliminating the increased thrombosis risk observed since 2011,” concluded the authors of the report.

Surgeons and cardiologists must now have a high index of suspicion for pump thrombosis in LVAD recipients, and be especially on the lookout for four key flags of a problem, said Dr. Kormos. The first is a rising LDH level, but additional flags include an isolated power elevation that doesn’t correlate with anything else, evidence of hemolysis, and new-onset heart failure symptoms. These can occur individually or in some combination. He recommended following a diagnostic algorithm first presented in 2013 that remains very valid today (J Heart Lung Transplant. 2013 July;32[7]:667-70).

Dr. Kormos also highlighted that the presentation of pump thrombosis can differ between the two LVADs most commonly used in U.S. practice, the HeartMate II and the HeartWare devices. A LDH elevation is primarily an indicator for HeartMate II, while both that model and the HeartWare device show sustained, isolated power elevations when thrombosis occurs.

Dr. Pagani, Dr. Kirklin, and Dr. Smedira had no disclosures. Dr. Kormos has received travel support from HeartWare. Dr. Kilic has been a consultant to Thoratec and a speaker on behalf of Baxter International.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

PHOENIX – Cardiothoracic surgeons who implant left ventricular assist devices in patients with failing hearts remain at a loss to fully explain why they started seeing a sharp increase in thrombus clogging in these devices in 2012, but nevertheless they are gaining a better sense of how to minimize the risk.

Three key principles for minimizing thrombosis risk are selecting the right patients to receive left ventricular assist devices (LVAD), applying optimal management strategies once patients receive a LVAD, and maintaining adequate flow of blood through the pump, Dr. Francis D. Pagani said in a talk at a session devoted to pump thrombosis at the annual meeting of the Society of Thoracic Surgeons.

Mitchel L. Zoler/Frontline Medical News

Other critical aspects include optimal implantation technique, quick work-up of patients to rule out reversible LVAD inflow or outflow problems once pump thrombosis is suspected, and ceasing medical therapy of the thrombosis if it proves ineffective and instead progress to surgical pump exchange, pump explantation, or heart transplant when necessary, said Dr. Ahmet Kilic, a cardiothoracic surgeon at the Ohio State University, Columbus.

Another key issue is that, now that the pump thrombosis incidence is averaging about 10% of LVAD recipients, with an incidence rate during 2-year follow-up as high as 24% reported from one series, surgeons and physicians who care for LVAD patients must have a high index of suspicion and routinely screen LVAD recipients for early signs of pump thrombosis. The best way to catch pump thrombosis early seems to be by regularly measuring patients’ serum level of lactate dehydrogenase (LDH), said Dr. Robert L. Kormos, professor of surgery and director of the artificial heart program at the University of Pittsburgh.

Mitchel L. Zoler/Frontline Medical News

“We measure LDH on most clinic visits, whether or not the patient has an indication of pump thrombosis. We need to screen [LDH levels] much more routinely than we used to,” he said during the session. “Elevated LDH is probably the first and most reliable early sign, but you need to also assess LDH isoenzymes because we’ve had patients with an elevation but no sign of pump thrombosis, and their isoenzymes showed that the increased LDH was coming from their liver,” Dr. Kormos said in an interview.

Although serial measurements and isoenzyme analysis can establish a sharp rise in heart-specific LDH in an individual patient, a report at the meeting documented that in a series of 53 patients with pump thrombosis treated at either of two U.S. centers, an LDH level of at least 1,155 IU/L flagged pump thrombosis with a fairly high sensitivity and specificity. This LDH level is roughly five times the upper limit of normal, noted Dr. Pagani, professor of surgery and surgical director of adult heart transplantation at the University of Michigan, Ann Arbor, and a senior author on this report.

But prior to this report Dr. Kormos said that he regarded a LDH level of 600-800 IU/L as enough of an elevation above normal to prompt concern and investigation. And he criticized some LVAD programs that allow LDH levels to rise much higher.

“I know of clinicians who see a LDH of 1,500-2,000 IU/L but the patient seems okay and they wonder if they should change out the pump. For me, it’s a no brainer. Others try to list a patient like this for a heart transplant so they can avoid doing a pump exchange. I think that’s dangerous; it risks liver failure or renal failure. I would not sit on any LVAD that is starting to produce signs of hemolysis syndrome, but some places do this,” Dr. Kormos said in an interview.

“Pump thrombosis probably did not get addressed in as timely a fashion as it should have been” when it was first seen on the rise in 2012, noted Dr. James K. Kirklin, professor of surgery and director of cardiothoracic surgery at the University of Alabama, Birmingham. “It is now being addressed, and we realize that this is not just a pump problem but also involves patient factors and management factors that we need to learn more about. We are quite ignorant of the patient factors and understanding their contributions to bleeding and thrombosis,” said Dr. Kirklin. He also acknowledged that whatever role the current generation of LVAD pumps play in causing thrombosis will not quickly resolve.

“I’m looking forward to a new generation of pumps, but the pumps we have today will probably remain for another 3-5 years.”

The issue of LVAD pump thrombosis first came into clear focus with publication at the start of 2014 of a report that tracked its incidence from 2004 to mid-2013 at three U.S. centers that had placed a total of 895 LVADs in 837 patients. The annual rate of new episodes of pump thrombosis jumped from about 1%-2% of LVAD recipients throughout the first part of the study period through the end of 2011, to an annual rate of about 10% by mid 2013 (N Engl J Med. 2014 Jan 2;370[1]:33-40).

“The inflection occurred in about 2012,” noted Dr. Nicholas G. Smedira, a cardiothoracic surgeon at the Cleveland Clinic. “No one has figured out why” the incidence suddenly spiked starting in 2012 and intensified in 2013, he said. This epidemic of pump thrombosis has produced “devastating complications” that have led to multiple readmissions and reduced cost-effectiveness of LVADs and has affected how the heart transplant community allocates hearts, Dr. Smedira said during his talk at the session. He noted that once the surge in pump thrombosis started, the timing of the appearance of significant thrombus shifted earlier, often occurring within 2-3 months after LVAD placement. There now is “increasing device-related pessimism” and increasing demoralization among clinicians because of this recurring complication, he said.

Mitchel L. Zoler/Frontline Medical News

More recent data show the trend toward increasingly higher rates of pump thrombosis continuing through the end of 2013, with the situation during 2014 a bit less clear. Late last year, data from 9,808 U.S. patients who received an LVAD and entered the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) showed that the incidence of pump thrombosis during the first 6 months following an implant rose from 1% in 2008 to 2% in 2009 and in 2010, 4% in 2011, 7% in 2012, 8% in 2013, and then eased back to 5% in the first half of 2014 (J Heart Lung Transplant. 2015 Dec;34[12]:1515-26). The annual rate rose from 2% in 2008 to a peak of 11% in 2013, with 12-month data from 2014 not yet available at the time of this report.

“The modest reduction of observed pump thrombosis at 6 months during 2014 has occurred in a milieu of heightened intensity of anti-coagulation management, greater surgical awareness of optimal pump implantation and positioning and pump speed management. Thus, one may speculate that current thrombosis risk-mitigation strategies have contributed to reducing but not eliminating the increased thrombosis risk observed since 2011,” concluded the authors of the report.

Surgeons and cardiologists must now have a high index of suspicion for pump thrombosis in LVAD recipients, and be especially on the lookout for four key flags of a problem, said Dr. Kormos. The first is a rising LDH level, but additional flags include an isolated power elevation that doesn’t correlate with anything else, evidence of hemolysis, and new-onset heart failure symptoms. These can occur individually or in some combination. He recommended following a diagnostic algorithm first presented in 2013 that remains very valid today (J Heart Lung Transplant. 2013 July;32[7]:667-70).

Dr. Kormos also highlighted that the presentation of pump thrombosis can differ between the two LVADs most commonly used in U.S. practice, the HeartMate II and the HeartWare devices. A LDH elevation is primarily an indicator for HeartMate II, while both that model and the HeartWare device show sustained, isolated power elevations when thrombosis occurs.

Dr. Pagani, Dr. Kirklin, and Dr. Smedira had no disclosures. Dr. Kormos has received travel support from HeartWare. Dr. Kilic has been a consultant to Thoratec and a speaker on behalf of Baxter International.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

LOS ANGELES – Adults who have migraine with aura had twice the rate of ischemic strokes, compared with people with migraine without aura in a review of 11,663 older Americans followed for an average of 18 years.

Migraine with aura appeared to increase the rate of cardioembolic strokes particularly, and the findings highlighted that middle-aged and older adults diagnosed with migraine with aura require special attention to interventions that could reduce their cardiovascular disease risks, Dr. Souvik Sen said in a video interview during the International Stroke Conference.

While results from prior studies have implicated migraine with aura as a risk factor for ischemic stroke, the new analysis was notable for involving an especially large number of community-dwelling older Americans, suggesting that the finding is broadly applicable to the general population of people with an average age of 58-60 years, said Dr. Sen, professor of clinical neurology and chairman of the department of neurology at the University of South Carolina in Columbia.

“It’s been known that migraine can increase the risk of stroke and that certain subgroups of migraine patients are especially important, such as patients with aura,” commented Dr. Ralph Sacco, professor and chairman of neurology at the University of Miami. “When I see patients with migraine I think about treating their migraine effectively and getting it under control, and putting even greater focus on controlling stroke risk factors. I also warn women with migraine about their increased stroke risk from using estrogen-containing oral contraceptives or hormone replacement,” Dr. Sacco noted.

Dr. Sen noted that the new analysis included people enrolled in the Atherosclerosis Risk in Communities (ARIC) study, which enrolled a random sample of more than 15,000 participants from four U.S. communities in 1987. The analysis focused on 11,663 people with migraine information collected during the third ARIC examination during 1993-1995, which identified 458 people (4%) who had migraine with aura, 1,158 (10%) who had migraine without aura, and 10,047 (86%) who were migraine free. During 18 years of follow-up the incidence of ischemic stroke among those with migraine with aura was twofold higher than among those with migraine without aura after adjustment for baseline rate of stroke risk factors, a statistically significant difference, he reported at the meeting sponsored by the American Heart Association. This difference seemed largely driven by a significant increase in the rate of cardioembolic strokes among the people with migraine with aura.

One hypothesis explaining the increased stroke rate in patients with aura is that, in patients with this presentation of migraine, the neurologic activity of migraine appears to spread to cerebral blood vessels and may affect blood flow within those vessels, Dr. Sen explained. It is also possible that migraine with aura may be a risk marker for or may predispose people to more extensive cardiovascular disease including atrial fibrillation.

The primary clinical implication of the finding is that people with migraine with aura should especially undergo a thorough assessment for cardiovascular disease risk factors, and should receive especially aggressive risk factor management, including controlling hypertension and smoking cessation, assessing ECG and atrial fibrillation, and avoiding estrogen treatment, Dr. Sen said.

 mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

LOS ANGELES – Adults who have migraine with aura had twice the rate of ischemic strokes, compared with people with migraine without aura in a review of 11,663 older Americans followed for an average of 18 years.

Migraine with aura appeared to increase the rate of cardioembolic strokes particularly, and the findings highlighted that middle-aged and older adults diagnosed with migraine with aura require special attention to interventions that could reduce their cardiovascular disease risks, Dr. Souvik Sen said in a video interview during the International Stroke Conference.

While results from prior studies have implicated migraine with aura as a risk factor for ischemic stroke, the new analysis was notable for involving an especially large number of community-dwelling older Americans, suggesting that the finding is broadly applicable to the general population of people with an average age of 58-60 years, said Dr. Sen, professor of clinical neurology and chairman of the department of neurology at the University of South Carolina in Columbia.

“It’s been known that migraine can increase the risk of stroke and that certain subgroups of migraine patients are especially important, such as patients with aura,” commented Dr. Ralph Sacco, professor and chairman of neurology at the University of Miami. “When I see patients with migraine I think about treating their migraine effectively and getting it under control, and putting even greater focus on controlling stroke risk factors. I also warn women with migraine about their increased stroke risk from using estrogen-containing oral contraceptives or hormone replacement,” Dr. Sacco noted.

Dr. Sen noted that the new analysis included people enrolled in the Atherosclerosis Risk in Communities (ARIC) study, which enrolled a random sample of more than 15,000 participants from four U.S. communities in 1987. The analysis focused on 11,663 people with migraine information collected during the third ARIC examination during 1993-1995, which identified 458 people (4%) who had migraine with aura, 1,158 (10%) who had migraine without aura, and 10,047 (86%) who were migraine free. During 18 years of follow-up the incidence of ischemic stroke among those with migraine with aura was twofold higher than among those with migraine without aura after adjustment for baseline rate of stroke risk factors, a statistically significant difference, he reported at the meeting sponsored by the American Heart Association. This difference seemed largely driven by a significant increase in the rate of cardioembolic strokes among the people with migraine with aura.

One hypothesis explaining the increased stroke rate in patients with aura is that, in patients with this presentation of migraine, the neurologic activity of migraine appears to spread to cerebral blood vessels and may affect blood flow within those vessels, Dr. Sen explained. It is also possible that migraine with aura may be a risk marker for or may predispose people to more extensive cardiovascular disease including atrial fibrillation.

The primary clinical implication of the finding is that people with migraine with aura should especially undergo a thorough assessment for cardiovascular disease risk factors, and should receive especially aggressive risk factor management, including controlling hypertension and smoking cessation, assessing ECG and atrial fibrillation, and avoiding estrogen treatment, Dr. Sen said.

 mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

LOS ANGELES – Adults who have migraine with aura had twice the rate of ischemic strokes, compared with people with migraine without aura in a review of 11,663 older Americans followed for an average of 18 years.

Migraine with aura appeared to increase the rate of cardioembolic strokes particularly, and the findings highlighted that middle-aged and older adults diagnosed with migraine with aura require special attention to interventions that could reduce their cardiovascular disease risks, Dr. Souvik Sen said in a video interview during the International Stroke Conference.

While results from prior studies have implicated migraine with aura as a risk factor for ischemic stroke, the new analysis was notable for involving an especially large number of community-dwelling older Americans, suggesting that the finding is broadly applicable to the general population of people with an average age of 58-60 years, said Dr. Sen, professor of clinical neurology and chairman of the department of neurology at the University of South Carolina in Columbia.

“It’s been known that migraine can increase the risk of stroke and that certain subgroups of migraine patients are especially important, such as patients with aura,” commented Dr. Ralph Sacco, professor and chairman of neurology at the University of Miami. “When I see patients with migraine I think about treating their migraine effectively and getting it under control, and putting even greater focus on controlling stroke risk factors. I also warn women with migraine about their increased stroke risk from using estrogen-containing oral contraceptives or hormone replacement,” Dr. Sacco noted.

Dr. Sen noted that the new analysis included people enrolled in the Atherosclerosis Risk in Communities (ARIC) study, which enrolled a random sample of more than 15,000 participants from four U.S. communities in 1987. The analysis focused on 11,663 people with migraine information collected during the third ARIC examination during 1993-1995, which identified 458 people (4%) who had migraine with aura, 1,158 (10%) who had migraine without aura, and 10,047 (86%) who were migraine free. During 18 years of follow-up the incidence of ischemic stroke among those with migraine with aura was twofold higher than among those with migraine without aura after adjustment for baseline rate of stroke risk factors, a statistically significant difference, he reported at the meeting sponsored by the American Heart Association. This difference seemed largely driven by a significant increase in the rate of cardioembolic strokes among the people with migraine with aura.

One hypothesis explaining the increased stroke rate in patients with aura is that, in patients with this presentation of migraine, the neurologic activity of migraine appears to spread to cerebral blood vessels and may affect blood flow within those vessels, Dr. Sen explained. It is also possible that migraine with aura may be a risk marker for or may predispose people to more extensive cardiovascular disease including atrial fibrillation.

The primary clinical implication of the finding is that people with migraine with aura should especially undergo a thorough assessment for cardiovascular disease risk factors, and should receive especially aggressive risk factor management, including controlling hypertension and smoking cessation, assessing ECG and atrial fibrillation, and avoiding estrogen treatment, Dr. Sen said.

 mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

The inflammatory skin disease hidradenitis suppurativa is associated with significantly increased risks of adverse cardiovascular outcomes such as ischemic stroke, myocardial infarction, and cardiovascular mortality, according to results of a population-based study.

A population-based cohort study of 5,964 patients with hidradenitis suppurativa showed that, after adjusting for confounders such as age, sex, smoking, and other comorbidities, hidradenitis suppurativa was associated with a 57% greater risk of myocardial infarction, 33% greater risk of ischemic stroke, 53% increase in major adverse cardiovascular events, and 35% increase in all-cause mortality over a mean 7.1 years of follow-up.

The study, published online Feb. 17 in JAMA Dermatology, also showed a significant increase in cardiovascular-associated death, which was the only adverse outcome that remained significantly elevated (incidence rate ratio, 1.58) in patients with hidradenitis suppurativa when compared with a control group of individuals with severe psoriasis (JAMA Dermatol. 2016 Feb 17. doi: 10.1001/jamadermatol.2015.6264).

“Studies have suggested that, in hidradenitis suppurativa, atrophy of the sebaceous glands, follicular hyperkeratinization, and subsequent hair follicle destruction are associated with deep-seated inflammation, increased susceptibility to secondary infections, and chronic perpetuation of the inflammatory response,” wrote Dr. Alexander Egeberg of the University of Copenhagen and coauthors.

The researchers suggested that there was a “conspicuous absence” of research reports on the risk of cardiovascular disease in hidradenitis suppurativa, especially in light of accumulating evidence of the association between cardiovascular disease and other chronic inflammatory diseases such as psoriasis, rheumatoid arthritis, and inflammatory bowel disease.

No conflicts of interest were declared.

The inflammatory skin disease hidradenitis suppurativa is associated with significantly increased risks of adverse cardiovascular outcomes such as ischemic stroke, myocardial infarction, and cardiovascular mortality, according to results of a population-based study.

A population-based cohort study of 5,964 patients with hidradenitis suppurativa showed that, after adjusting for confounders such as age, sex, smoking, and other comorbidities, hidradenitis suppurativa was associated with a 57% greater risk of myocardial infarction, 33% greater risk of ischemic stroke, 53% increase in major adverse cardiovascular events, and 35% increase in all-cause mortality over a mean 7.1 years of follow-up.

The study, published online Feb. 17 in JAMA Dermatology, also showed a significant increase in cardiovascular-associated death, which was the only adverse outcome that remained significantly elevated (incidence rate ratio, 1.58) in patients with hidradenitis suppurativa when compared with a control group of individuals with severe psoriasis (JAMA Dermatol. 2016 Feb 17. doi: 10.1001/jamadermatol.2015.6264).

“Studies have suggested that, in hidradenitis suppurativa, atrophy of the sebaceous glands, follicular hyperkeratinization, and subsequent hair follicle destruction are associated with deep-seated inflammation, increased susceptibility to secondary infections, and chronic perpetuation of the inflammatory response,” wrote Dr. Alexander Egeberg of the University of Copenhagen and coauthors.

The researchers suggested that there was a “conspicuous absence” of research reports on the risk of cardiovascular disease in hidradenitis suppurativa, especially in light of accumulating evidence of the association between cardiovascular disease and other chronic inflammatory diseases such as psoriasis, rheumatoid arthritis, and inflammatory bowel disease.

No conflicts of interest were declared.

The inflammatory skin disease hidradenitis suppurativa is associated with significantly increased risks of adverse cardiovascular outcomes such as ischemic stroke, myocardial infarction, and cardiovascular mortality, according to results of a population-based study.

A population-based cohort study of 5,964 patients with hidradenitis suppurativa showed that, after adjusting for confounders such as age, sex, smoking, and other comorbidities, hidradenitis suppurativa was associated with a 57% greater risk of myocardial infarction, 33% greater risk of ischemic stroke, 53% increase in major adverse cardiovascular events, and 35% increase in all-cause mortality over a mean 7.1 years of follow-up.

The study, published online Feb. 17 in JAMA Dermatology, also showed a significant increase in cardiovascular-associated death, which was the only adverse outcome that remained significantly elevated (incidence rate ratio, 1.58) in patients with hidradenitis suppurativa when compared with a control group of individuals with severe psoriasis (JAMA Dermatol. 2016 Feb 17. doi: 10.1001/jamadermatol.2015.6264).

“Studies have suggested that, in hidradenitis suppurativa, atrophy of the sebaceous glands, follicular hyperkeratinization, and subsequent hair follicle destruction are associated with deep-seated inflammation, increased susceptibility to secondary infections, and chronic perpetuation of the inflammatory response,” wrote Dr. Alexander Egeberg of the University of Copenhagen and coauthors.

The researchers suggested that there was a “conspicuous absence” of research reports on the risk of cardiovascular disease in hidradenitis suppurativa, especially in light of accumulating evidence of the association between cardiovascular disease and other chronic inflammatory diseases such as psoriasis, rheumatoid arthritis, and inflammatory bowel disease.

No conflicts of interest were declared.

A diagnosis of influenza increased the risk of subsequent atrial fibrillation by about 18%, investigators reported online in Heart Rhythm.

Clinicians therefore should consider atrial fibrillation (AF) in patients with influenza-like symptoms who report palpitations or experience an ischemic stroke, said Dr. Ting-Yung Chang of Taipei Veterans General Hospital in Taiwan and his associates. Influenza vaccination might help prevent AF, and high-risk patients should be encouraged to receive the vaccination annually, they said. However, a large prospective study is needed to clarify whether influenza vaccination reduces the risk of AF and subsequent ischemic stroke and systemic thromboembolic events, they added.

©Graça Victoria/Thinkstockphotos.com

Atrial fibrillation increases the risk of stroke about fivefold, triples the risk of heart failure, and doubles the chances of dementia and death, the researchers noted. Mounting evidence implicates inflammation and sympathetic nervous system dysregulation in the pathogenesis of AF, raising questions about whether influenza might underlie or contribute to some cases of AF. To explore relationships among AF, influenza, and influenza vaccination, the investigators analyzed data for 11,374 patients with AF who were enrolled in the Taiwan National Health Insurance Research Database between 2000 and 2010. They matched each patient with AF to four controls based on age, sex, enrollment date, and the Charlson comorbidity index (

Heart Rhythm. 2016 Feb. doi: 10.1016/j.hrthm.2016.01.026

).

Unvaccinated patients with influenza were 18% more likely to develop AF than unvaccinated patients without influenza (odds ratio, 1.18; 95% confidence interval, 1.01-1.38; P = .032), even after adjusting for demographic factors, medical history, and use of relevant health care services, the researchers reported. In contrast, vaccinated patients who later developed influenza were about as likely to develop AF as unvaccinated patients who did not develop influenza, both in the overall analysis and in subgroups stratified by age, sex, and comorbidities. Moreover, vaccinated patients without influenza were even less likely to develop AF than unvaccinated patients without influenza (OR, 0.88; 95% CI, 0.84-0.93; P less than .001).

The registry database excluded relevant data on smoking history, body mass index, and physical activity level, the researchers said. “Influenza infection was diagnosed using ICD-9 codes with concomitant use of antiviral agents, and was not further confirmed based on the results of viral culture with throat swab,” they added. “The diagnostic accuracy of influenza infection cannot be fully ascertained.”

The National Science Council and the Taipei Veterans General Hospital funded the study. The researchers had no disclosures.

A diagnosis of influenza increased the risk of subsequent atrial fibrillation by about 18%, investigators reported online in Heart Rhythm.

Clinicians therefore should consider atrial fibrillation (AF) in patients with influenza-like symptoms who report palpitations or experience an ischemic stroke, said Dr. Ting-Yung Chang of Taipei Veterans General Hospital in Taiwan and his associates. Influenza vaccination might help prevent AF, and high-risk patients should be encouraged to receive the vaccination annually, they said. However, a large prospective study is needed to clarify whether influenza vaccination reduces the risk of AF and subsequent ischemic stroke and systemic thromboembolic events, they added.

©Graça Victoria/Thinkstockphotos.com

Atrial fibrillation increases the risk of stroke about fivefold, triples the risk of heart failure, and doubles the chances of dementia and death, the researchers noted. Mounting evidence implicates inflammation and sympathetic nervous system dysregulation in the pathogenesis of AF, raising questions about whether influenza might underlie or contribute to some cases of AF. To explore relationships among AF, influenza, and influenza vaccination, the investigators analyzed data for 11,374 patients with AF who were enrolled in the Taiwan National Health Insurance Research Database between 2000 and 2010. They matched each patient with AF to four controls based on age, sex, enrollment date, and the Charlson comorbidity index (

Heart Rhythm. 2016 Feb. doi: 10.1016/j.hrthm.2016.01.026

).

Unvaccinated patients with influenza were 18% more likely to develop AF than unvaccinated patients without influenza (odds ratio, 1.18; 95% confidence interval, 1.01-1.38; P = .032), even after adjusting for demographic factors, medical history, and use of relevant health care services, the researchers reported. In contrast, vaccinated patients who later developed influenza were about as likely to develop AF as unvaccinated patients who did not develop influenza, both in the overall analysis and in subgroups stratified by age, sex, and comorbidities. Moreover, vaccinated patients without influenza were even less likely to develop AF than unvaccinated patients without influenza (OR, 0.88; 95% CI, 0.84-0.93; P less than .001).

The registry database excluded relevant data on smoking history, body mass index, and physical activity level, the researchers said. “Influenza infection was diagnosed using ICD-9 codes with concomitant use of antiviral agents, and was not further confirmed based on the results of viral culture with throat swab,” they added. “The diagnostic accuracy of influenza infection cannot be fully ascertained.”

The National Science Council and the Taipei Veterans General Hospital funded the study. The researchers had no disclosures.

A diagnosis of influenza increased the risk of subsequent atrial fibrillation by about 18%, investigators reported online in Heart Rhythm.

Clinicians therefore should consider atrial fibrillation (AF) in patients with influenza-like symptoms who report palpitations or experience an ischemic stroke, said Dr. Ting-Yung Chang of Taipei Veterans General Hospital in Taiwan and his associates. Influenza vaccination might help prevent AF, and high-risk patients should be encouraged to receive the vaccination annually, they said. However, a large prospective study is needed to clarify whether influenza vaccination reduces the risk of AF and subsequent ischemic stroke and systemic thromboembolic events, they added.

©Graça Victoria/Thinkstockphotos.com

Atrial fibrillation increases the risk of stroke about fivefold, triples the risk of heart failure, and doubles the chances of dementia and death, the researchers noted. Mounting evidence implicates inflammation and sympathetic nervous system dysregulation in the pathogenesis of AF, raising questions about whether influenza might underlie or contribute to some cases of AF. To explore relationships among AF, influenza, and influenza vaccination, the investigators analyzed data for 11,374 patients with AF who were enrolled in the Taiwan National Health Insurance Research Database between 2000 and 2010. They matched each patient with AF to four controls based on age, sex, enrollment date, and the Charlson comorbidity index (

Heart Rhythm. 2016 Feb. doi: 10.1016/j.hrthm.2016.01.026

).

Unvaccinated patients with influenza were 18% more likely to develop AF than unvaccinated patients without influenza (odds ratio, 1.18; 95% confidence interval, 1.01-1.38; P = .032), even after adjusting for demographic factors, medical history, and use of relevant health care services, the researchers reported. In contrast, vaccinated patients who later developed influenza were about as likely to develop AF as unvaccinated patients who did not develop influenza, both in the overall analysis and in subgroups stratified by age, sex, and comorbidities. Moreover, vaccinated patients without influenza were even less likely to develop AF than unvaccinated patients without influenza (OR, 0.88; 95% CI, 0.84-0.93; P less than .001).

The registry database excluded relevant data on smoking history, body mass index, and physical activity level, the researchers said. “Influenza infection was diagnosed using ICD-9 codes with concomitant use of antiviral agents, and was not further confirmed based on the results of viral culture with throat swab,” they added. “The diagnostic accuracy of influenza infection cannot be fully ascertained.”

The National Science Council and the Taipei Veterans General Hospital funded the study. The researchers had no disclosures.

SNOWMASS, COLO. – The goal is finally in sight following an odyssey to develop the Watchman left atrial appendage closure device as a safe and effective alternative to oral anticoagulation for stroke prevention in patients with nonvalvular atrial fibrillation, Dr. David R. Holmes Jr. said at the Annual Cardiovascular Conference at Snowmass.

It’s all coming together: The Watchman, a small percutaneously delivered parachute-like device, has received FDA marketing approval as the sole authorized left atrial appendage closure device in this country on the strength of two compellingly positive randomized controlled trials. A recent meta-analysis of those trials showed significantly fewer hemorrhagic strokes, fewer cardiovascular or unexplained deaths, and fewer nonprocedural bleeding events in Watchman recipients than in patients randomized to warfarin. And a cost-effectiveness analysis has concluded that after 8 years, the Watchman becomes “the dominant strategy” – meaning more effective and less costly for stroke prevention in patients with atrial fibrillation (AF) having a contraindication to warfarin – compared with the novel oral anticoagulant apixaban (J Am Coll Cardiol. 2015 Dec 22;66[24]:2728-39).

Moreover, the final pieces required for the Watchman to become a mainstream reimbursable therapy are falling into place. The Society for Cardiovascular Angiography and Interventions (SCAI), the American College of Cardiology, and the Heart Rhythm Society (HRS) have jointly issued institutional and operator requirements for left atrial appendage occlusion programs (J Am Coll Cardiol. 2015 Dec 8. pii: S0735-1097[15]07550-6). The ACC’s National Cardiovascular Data Registry has set up a new left atrial occlusion registry. And most important of all from a reimbursement standpoint, the Centers for Medicare and Medicaid Services has released a preliminary National Coverage Determination for left atrial appendage occlusion.

“This will affect your patients and your lives,” noted Dr. Holmes of the Mayo Clinic in Rochester, Minn. He and the Mayo Clinic share a financial interest in the Watchman technology, which has been licensed to Boston Scientific.

The CMS will cover the Watchman only when the catheter procedure is performed by an experienced interventional cardiologist or electrophysiologist in an experienced center as defined by the SCAI/ACC/HRS standards, and only in patients enrolled in the national prospective registry. The registry will monitor operator and device-related complications, stroke and systemic embolism rates, deaths, and major bleeding rates for 5 years post-procedure.

“If you want to be in this field, you will be in that registry because reimbursement will depend on that,” Dr. Holmes explained. “This registry will be incredibly important. It will tell us how we’re doing, what we should be doing, and what we could potentially be doing in the future.”

One hitch is that the preliminary National Coverage Determination states that coverage will be limited to AF patients with high stroke-risk and HAS-BLED scores as well as a contraindication to warfarin, whereas the FDA-approved indication says patients must be deemed by their physician to be suitable for warfarin.

“In this particular case, CMS was not talking with FDA. We don’t know how that will get sorted out,” according to the cardiologist. “But as soon as CMS comes through with their final regulatory coverage determination, I think we will finally be there. We’ll then be able to offer this as a treatment strategy for stroke prevention in selected patients with atrial fibrillation, realizing that with this device there’s a 40% reduction in the composite endpoint of cardiovascular or unexplained death, stroke, and systemic embolism compared to warfarin.”

That figure of a 40% relative risk reduction comes from the 46-month follow-up data in the randomized PROTECT AF trial (JAMA. 2014 Nov 19;312[19]:1988-98).

More recently, Dr. Holmes and his coinvestigators published a patient-level meta-analysis of data from PROTECT AF and PREVAIL, the other randomized trial of the Watchman versus warfarin. They reported that Watchman recipients had a 78% reduction in hemorrhagic strokes, a 52% reduction in cardiovascular or unexplained deaths, and a 49% lower rate of nonprocedural bleeding, compared with patients assigned to warfarin (J Am Coll Cardiol. 2015 Jun 23;65[24]:2614-23).

There have been no randomized trials comparing the Watchman to novel oral anticoagulants.

Dr. Holmes said the worldwide experience to date has been that roughly 95% of AF patients are able to safely go off warfarin or a novel oral anticoagulant 12 months after Watchman placement.

“So instead of taking eight drugs when you’re 75 years old, you can take seven. Most patients think that’s a pretty good deal,” the cardiologist observed.

Session moderator Dr. Samuel J. Asirvatham posed a question: Since recurrence of AF following catheter ablation is common and it’s now thought that up to 20% of AF arises from foci located in the left atrial appendage, what about combining standard catheter ablation of AF via pulmonary vein isolation with placement of the Watchman in a single procedure?

If such a combined procedure can be done efficiently, it should enable recipients of AF catheter ablation to safely go off oral anticoagulation, noted Dr. Asirvatham, an electrophysiologist who is professor of medicine and pediatrics at the Mayo Clinic, Rochester, Minn.

Dr. Holmes said several small studies of patients who have received combined AF ablation and Watchman implantation have been published.

“It’s uncertain whether left atrial appendage closure will affect AF recurrence rates post ablation, but it should reduce stroke risk. It’s a terribly important field of exploration that will be pursued in registries both in Europe and the United States,” he said.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – The goal is finally in sight following an odyssey to develop the Watchman left atrial appendage closure device as a safe and effective alternative to oral anticoagulation for stroke prevention in patients with nonvalvular atrial fibrillation, Dr. David R. Holmes Jr. said at the Annual Cardiovascular Conference at Snowmass.

It’s all coming together: The Watchman, a small percutaneously delivered parachute-like device, has received FDA marketing approval as the sole authorized left atrial appendage closure device in this country on the strength of two compellingly positive randomized controlled trials. A recent meta-analysis of those trials showed significantly fewer hemorrhagic strokes, fewer cardiovascular or unexplained deaths, and fewer nonprocedural bleeding events in Watchman recipients than in patients randomized to warfarin. And a cost-effectiveness analysis has concluded that after 8 years, the Watchman becomes “the dominant strategy” – meaning more effective and less costly for stroke prevention in patients with atrial fibrillation (AF) having a contraindication to warfarin – compared with the novel oral anticoagulant apixaban (J Am Coll Cardiol. 2015 Dec 22;66[24]:2728-39).

Moreover, the final pieces required for the Watchman to become a mainstream reimbursable therapy are falling into place. The Society for Cardiovascular Angiography and Interventions (SCAI), the American College of Cardiology, and the Heart Rhythm Society (HRS) have jointly issued institutional and operator requirements for left atrial appendage occlusion programs (J Am Coll Cardiol. 2015 Dec 8. pii: S0735-1097[15]07550-6). The ACC’s National Cardiovascular Data Registry has set up a new left atrial occlusion registry. And most important of all from a reimbursement standpoint, the Centers for Medicare and Medicaid Services has released a preliminary National Coverage Determination for left atrial appendage occlusion.

“This will affect your patients and your lives,” noted Dr. Holmes of the Mayo Clinic in Rochester, Minn. He and the Mayo Clinic share a financial interest in the Watchman technology, which has been licensed to Boston Scientific.

The CMS will cover the Watchman only when the catheter procedure is performed by an experienced interventional cardiologist or electrophysiologist in an experienced center as defined by the SCAI/ACC/HRS standards, and only in patients enrolled in the national prospective registry. The registry will monitor operator and device-related complications, stroke and systemic embolism rates, deaths, and major bleeding rates for 5 years post-procedure.

“If you want to be in this field, you will be in that registry because reimbursement will depend on that,” Dr. Holmes explained. “This registry will be incredibly important. It will tell us how we’re doing, what we should be doing, and what we could potentially be doing in the future.”

One hitch is that the preliminary National Coverage Determination states that coverage will be limited to AF patients with high stroke-risk and HAS-BLED scores as well as a contraindication to warfarin, whereas the FDA-approved indication says patients must be deemed by their physician to be suitable for warfarin.

“In this particular case, CMS was not talking with FDA. We don’t know how that will get sorted out,” according to the cardiologist. “But as soon as CMS comes through with their final regulatory coverage determination, I think we will finally be there. We’ll then be able to offer this as a treatment strategy for stroke prevention in selected patients with atrial fibrillation, realizing that with this device there’s a 40% reduction in the composite endpoint of cardiovascular or unexplained death, stroke, and systemic embolism compared to warfarin.”

That figure of a 40% relative risk reduction comes from the 46-month follow-up data in the randomized PROTECT AF trial (JAMA. 2014 Nov 19;312[19]:1988-98).

More recently, Dr. Holmes and his coinvestigators published a patient-level meta-analysis of data from PROTECT AF and PREVAIL, the other randomized trial of the Watchman versus warfarin. They reported that Watchman recipients had a 78% reduction in hemorrhagic strokes, a 52% reduction in cardiovascular or unexplained deaths, and a 49% lower rate of nonprocedural bleeding, compared with patients assigned to warfarin (J Am Coll Cardiol. 2015 Jun 23;65[24]:2614-23).

There have been no randomized trials comparing the Watchman to novel oral anticoagulants.

Dr. Holmes said the worldwide experience to date has been that roughly 95% of AF patients are able to safely go off warfarin or a novel oral anticoagulant 12 months after Watchman placement.

“So instead of taking eight drugs when you’re 75 years old, you can take seven. Most patients think that’s a pretty good deal,” the cardiologist observed.

Session moderator Dr. Samuel J. Asirvatham posed a question: Since recurrence of AF following catheter ablation is common and it’s now thought that up to 20% of AF arises from foci located in the left atrial appendage, what about combining standard catheter ablation of AF via pulmonary vein isolation with placement of the Watchman in a single procedure?

If such a combined procedure can be done efficiently, it should enable recipients of AF catheter ablation to safely go off oral anticoagulation, noted Dr. Asirvatham, an electrophysiologist who is professor of medicine and pediatrics at the Mayo Clinic, Rochester, Minn.

Dr. Holmes said several small studies of patients who have received combined AF ablation and Watchman implantation have been published.

“It’s uncertain whether left atrial appendage closure will affect AF recurrence rates post ablation, but it should reduce stroke risk. It’s a terribly important field of exploration that will be pursued in registries both in Europe and the United States,” he said.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – The goal is finally in sight following an odyssey to develop the Watchman left atrial appendage closure device as a safe and effective alternative to oral anticoagulation for stroke prevention in patients with nonvalvular atrial fibrillation, Dr. David R. Holmes Jr. said at the Annual Cardiovascular Conference at Snowmass.

It’s all coming together: The Watchman, a small percutaneously delivered parachute-like device, has received FDA marketing approval as the sole authorized left atrial appendage closure device in this country on the strength of two compellingly positive randomized controlled trials. A recent meta-analysis of those trials showed significantly fewer hemorrhagic strokes, fewer cardiovascular or unexplained deaths, and fewer nonprocedural bleeding events in Watchman recipients than in patients randomized to warfarin. And a cost-effectiveness analysis has concluded that after 8 years, the Watchman becomes “the dominant strategy” – meaning more effective and less costly for stroke prevention in patients with atrial fibrillation (AF) having a contraindication to warfarin – compared with the novel oral anticoagulant apixaban (J Am Coll Cardiol. 2015 Dec 22;66[24]:2728-39).

Moreover, the final pieces required for the Watchman to become a mainstream reimbursable therapy are falling into place. The Society for Cardiovascular Angiography and Interventions (SCAI), the American College of Cardiology, and the Heart Rhythm Society (HRS) have jointly issued institutional and operator requirements for left atrial appendage occlusion programs (J Am Coll Cardiol. 2015 Dec 8. pii: S0735-1097[15]07550-6). The ACC’s National Cardiovascular Data Registry has set up a new left atrial occlusion registry. And most important of all from a reimbursement standpoint, the Centers for Medicare and Medicaid Services has released a preliminary National Coverage Determination for left atrial appendage occlusion.

“This will affect your patients and your lives,” noted Dr. Holmes of the Mayo Clinic in Rochester, Minn. He and the Mayo Clinic share a financial interest in the Watchman technology, which has been licensed to Boston Scientific.

The CMS will cover the Watchman only when the catheter procedure is performed by an experienced interventional cardiologist or electrophysiologist in an experienced center as defined by the SCAI/ACC/HRS standards, and only in patients enrolled in the national prospective registry. The registry will monitor operator and device-related complications, stroke and systemic embolism rates, deaths, and major bleeding rates for 5 years post-procedure.

“If you want to be in this field, you will be in that registry because reimbursement will depend on that,” Dr. Holmes explained. “This registry will be incredibly important. It will tell us how we’re doing, what we should be doing, and what we could potentially be doing in the future.”

One hitch is that the preliminary National Coverage Determination states that coverage will be limited to AF patients with high stroke-risk and HAS-BLED scores as well as a contraindication to warfarin, whereas the FDA-approved indication says patients must be deemed by their physician to be suitable for warfarin.

“In this particular case, CMS was not talking with FDA. We don’t know how that will get sorted out,” according to the cardiologist. “But as soon as CMS comes through with their final regulatory coverage determination, I think we will finally be there. We’ll then be able to offer this as a treatment strategy for stroke prevention in selected patients with atrial fibrillation, realizing that with this device there’s a 40% reduction in the composite endpoint of cardiovascular or unexplained death, stroke, and systemic embolism compared to warfarin.”

That figure of a 40% relative risk reduction comes from the 46-month follow-up data in the randomized PROTECT AF trial (JAMA. 2014 Nov 19;312[19]:1988-98).

More recently, Dr. Holmes and his coinvestigators published a patient-level meta-analysis of data from PROTECT AF and PREVAIL, the other randomized trial of the Watchman versus warfarin. They reported that Watchman recipients had a 78% reduction in hemorrhagic strokes, a 52% reduction in cardiovascular or unexplained deaths, and a 49% lower rate of nonprocedural bleeding, compared with patients assigned to warfarin (J Am Coll Cardiol. 2015 Jun 23;65[24]:2614-23).

There have been no randomized trials comparing the Watchman to novel oral anticoagulants.

Dr. Holmes said the worldwide experience to date has been that roughly 95% of AF patients are able to safely go off warfarin or a novel oral anticoagulant 12 months after Watchman placement.

“So instead of taking eight drugs when you’re 75 years old, you can take seven. Most patients think that’s a pretty good deal,” the cardiologist observed.

Session moderator Dr. Samuel J. Asirvatham posed a question: Since recurrence of AF following catheter ablation is common and it’s now thought that up to 20% of AF arises from foci located in the left atrial appendage, what about combining standard catheter ablation of AF via pulmonary vein isolation with placement of the Watchman in a single procedure?

If such a combined procedure can be done efficiently, it should enable recipients of AF catheter ablation to safely go off oral anticoagulation, noted Dr. Asirvatham, an electrophysiologist who is professor of medicine and pediatrics at the Mayo Clinic, Rochester, Minn.

Dr. Holmes said several small studies of patients who have received combined AF ablation and Watchman implantation have been published.

“It’s uncertain whether left atrial appendage closure will affect AF recurrence rates post ablation, but it should reduce stroke risk. It’s a terribly important field of exploration that will be pursued in registries both in Europe and the United States,” he said.

bjancin@frontlinemedcom.com