Stroke

A Food and Drug Administration advisory panel struggled to muster support for marketing clearance of the TriGuard 3 (Keystone Heart) device for use during transcatheter aortic valve replacement (TAVR).

The Circulatory Systems Devices Panel of the Medical Devices Advisory Committee took no vote when it met Aug. 3, but weighed evidence for a proposed indication for the device “to minimize the risk of cerebral damage by deflecting embolic debris away from the cerebral circulation” during TAVR.

“While this device may deflect some debris, the data would suggest it may also create issues,” said Keith B. Allen, MD, director of surgical research at the Mid America Heart & Lung Surgeons, Kansas City, Mo. “I am really concerned that our desire and the emotion that surrounds preventing stroke are not being supported by the data.”

TriGuard 3 received CE Mark in Europe in March 2020. It was submitted for 510(k) clearance and seeks to prove substantial equivalence to the predicate Sentinel device (Claret Medical), currently the only approved embolic protection device in the United States.

The device is designed to cover all three major aortic vessels (innominate, left carotid, and left subclavian arteries) and is delivered transfemorally through an 8F sheath, whereas the Sentinel is positioned within the branch vessels, doesn’t cover the left subclavian artery, and is introduced through the radial or brachial artery via a 6F sheath.

TriGuard 3 faced an uphill battle, however, after failing to meet the primary composite efficacy endpoint in the REFLECT phase 2 trial (P = .857), with numeric trends showing higher all-cause mortality or any stroke at 30 days (9.8% vs. 6.7%) than pooled control subjects without embolic protection.

Rates for other components of the endpoint also trended higher with the device: National Institutes of Stroke Stroke Scale score worsening 2-5 days after the procedure, cerebral ischemic lesions on MRI 2-5 days after the procedure, and total cerebral ischemic lesion volume.

The Sentinel device was approved in 2017 after it failed to meet its primary efficacy endpoint of new brain lesion volume on MRI, but death and stroke rates favored the device over control, the panel pointed out.

The sponsor provided additional analyses in the per treatment (PT) population, defined as those with complete three-vessel coverage in at least two of three procedural time points. Compared with pooled control subjects, most of the imaging endpoints favored the TriGuard 3 device, but clinical neurologic event rates continued to favor the control group.

“The data used to demonstrate efficacy are all based on the PT subpopulation of the whole population, and those have to be considered promissory data,” said John Hirshfeld, MD, emeritus professor, University of Pennsylvania, Philadelphia. “This is the group where everything went well and for us to decide that’s achievable in the general population is speculative.”
 

Safety data

The REFLECT trial did meet its primary safety endpoint, with a 30-day major adverse cardiovascular event rate of 15.9%, compared with a performance goal of 34.4% (P < .0001).

Although prespecified, panel members pushed back, saying that the performance goal was unacceptably high, with several members remarking they’d never heard of a trial adding 9% as a “fudge factor” to a 25% historic control rate to get to the 34% performance target.

Keystone health officials noted that REFLECT was not designed to demonstrate a significant difference in the rate of primary safety events, compared with control. Instead, its purpose was to demonstrate that TriGuard 3 did not increase the risk associated with a TAVR procedure.

The TriGuard 3 device was successfully placed and retrieved in 100% of patients, but complete coverage was not uniform, with 72% of 157 as-treated patients having complete three-vessel coverage post TAVR but 15% having no coverage.

Panel members also expressed concern over device interference during TAVR, which was reported in nearly 10% of all TriGuard patients.

The TriGuard 3 group had 11 major vascular complications, 2 directly related to the device, and 3 stage 3 acute kidney injuries, whereas neither complication occurred in the control group.

Throughout the 9-hour hearing, the panel wrestled with what was described as a highly select patient group and small patient numbers that made it difficult to interpret observed differences. The trial involved 157 TriGuard 3 patients (including 41 from the roll-in phase) and 119 control subjects pooled from phase 2 of the trial (n = 57) and from phase 1 using the early-stage TriGuard HDH device (n = 57).

Pieter Stella, MD, PhD, Utrecht (the Netherlands) Medical Center, also presented “real-world” evidence from 75 patients in the Netherlands using the latest iteration of the device available in Europe with updates to the crimper and additional training materials to prevent the device from torquing during delivery. No strokes were reported, one patient had a transient ischemic attack (TIA), and two patients had a dissection, which resolved without sequelae.

Ralph Brindis, MD, MPH, professor of medicine, University of California, San Francisco, countered that there were only three experienced operators from a single center and that the stroke incidence was physician reported, “not data we can really embrace.”

There was much debate over why enrollment in phase 2 of the RHYTHM trial was temporarily paused in February 2019, briefly restarted, and then prematurely stopped in April 2019.

FDA officials said the study was paused at the recommendation of the data monitoring committee (DMC) because rates of safety events were different between patients and control subjects and operational errors called into question the accuracy of the data being reviewed. Ultimately, both the DMC and FDA recommended study suspension.

During the public hearing, TAVR pioneer Alain Cribier, MD, University of Rouen’s Charles Nicolle Hospital, Mont-Saint-Aignan, France, said the TriGuard 3 is of interest because it can be used with minimal need for manipulation and complete coverage of the cerebral vessels that is achieved by diverting rather than capturing debris. “The rapid and exponential growth of TAVR procedures demands safe TAVR interventions and the use of cerebral protection devices is a step in this direction.”

Others took a dim view. “Given that the Sentinel device has not demonstrated benefit on clinical outcomes, there is significant concern about similar devices, such as the TriGuard 3, providing clinical benefit,” Rita Redberg, MD, Sanket Dhruva, MD, and Robin Ji, University of California, San Francisco, wrote in a letter submitted to the panel.

Commenting further, they added: “With the results from the REFLECT II trial demonstrating no evidence for clinical outcome benefit in TAVR patients, and numerically higher rates for stroke risk, mortality, bleeding risk, and other dangerous adverse complications among those treated, it is concerning and dangerous for patient safety that the TriGUARD 3 cerebral embolic protection device is being considered for FDA 510(k) clearance.”

The FDA panel members reported no financial relationships.

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

A Food and Drug Administration advisory panel struggled to muster support for marketing clearance of the TriGuard 3 (Keystone Heart) device for use during transcatheter aortic valve replacement (TAVR).

The Circulatory Systems Devices Panel of the Medical Devices Advisory Committee took no vote when it met Aug. 3, but weighed evidence for a proposed indication for the device “to minimize the risk of cerebral damage by deflecting embolic debris away from the cerebral circulation” during TAVR.

“While this device may deflect some debris, the data would suggest it may also create issues,” said Keith B. Allen, MD, director of surgical research at the Mid America Heart & Lung Surgeons, Kansas City, Mo. “I am really concerned that our desire and the emotion that surrounds preventing stroke are not being supported by the data.”

TriGuard 3 received CE Mark in Europe in March 2020. It was submitted for 510(k) clearance and seeks to prove substantial equivalence to the predicate Sentinel device (Claret Medical), currently the only approved embolic protection device in the United States.

The device is designed to cover all three major aortic vessels (innominate, left carotid, and left subclavian arteries) and is delivered transfemorally through an 8F sheath, whereas the Sentinel is positioned within the branch vessels, doesn’t cover the left subclavian artery, and is introduced through the radial or brachial artery via a 6F sheath.

TriGuard 3 faced an uphill battle, however, after failing to meet the primary composite efficacy endpoint in the REFLECT phase 2 trial (P = .857), with numeric trends showing higher all-cause mortality or any stroke at 30 days (9.8% vs. 6.7%) than pooled control subjects without embolic protection.

Rates for other components of the endpoint also trended higher with the device: National Institutes of Stroke Stroke Scale score worsening 2-5 days after the procedure, cerebral ischemic lesions on MRI 2-5 days after the procedure, and total cerebral ischemic lesion volume.

The Sentinel device was approved in 2017 after it failed to meet its primary efficacy endpoint of new brain lesion volume on MRI, but death and stroke rates favored the device over control, the panel pointed out.

The sponsor provided additional analyses in the per treatment (PT) population, defined as those with complete three-vessel coverage in at least two of three procedural time points. Compared with pooled control subjects, most of the imaging endpoints favored the TriGuard 3 device, but clinical neurologic event rates continued to favor the control group.

“The data used to demonstrate efficacy are all based on the PT subpopulation of the whole population, and those have to be considered promissory data,” said John Hirshfeld, MD, emeritus professor, University of Pennsylvania, Philadelphia. “This is the group where everything went well and for us to decide that’s achievable in the general population is speculative.”
 

Safety data

The REFLECT trial did meet its primary safety endpoint, with a 30-day major adverse cardiovascular event rate of 15.9%, compared with a performance goal of 34.4% (P < .0001).

Although prespecified, panel members pushed back, saying that the performance goal was unacceptably high, with several members remarking they’d never heard of a trial adding 9% as a “fudge factor” to a 25% historic control rate to get to the 34% performance target.

Keystone health officials noted that REFLECT was not designed to demonstrate a significant difference in the rate of primary safety events, compared with control. Instead, its purpose was to demonstrate that TriGuard 3 did not increase the risk associated with a TAVR procedure.

The TriGuard 3 device was successfully placed and retrieved in 100% of patients, but complete coverage was not uniform, with 72% of 157 as-treated patients having complete three-vessel coverage post TAVR but 15% having no coverage.

Panel members also expressed concern over device interference during TAVR, which was reported in nearly 10% of all TriGuard patients.

The TriGuard 3 group had 11 major vascular complications, 2 directly related to the device, and 3 stage 3 acute kidney injuries, whereas neither complication occurred in the control group.

Throughout the 9-hour hearing, the panel wrestled with what was described as a highly select patient group and small patient numbers that made it difficult to interpret observed differences. The trial involved 157 TriGuard 3 patients (including 41 from the roll-in phase) and 119 control subjects pooled from phase 2 of the trial (n = 57) and from phase 1 using the early-stage TriGuard HDH device (n = 57).

Pieter Stella, MD, PhD, Utrecht (the Netherlands) Medical Center, also presented “real-world” evidence from 75 patients in the Netherlands using the latest iteration of the device available in Europe with updates to the crimper and additional training materials to prevent the device from torquing during delivery. No strokes were reported, one patient had a transient ischemic attack (TIA), and two patients had a dissection, which resolved without sequelae.

Ralph Brindis, MD, MPH, professor of medicine, University of California, San Francisco, countered that there were only three experienced operators from a single center and that the stroke incidence was physician reported, “not data we can really embrace.”

There was much debate over why enrollment in phase 2 of the RHYTHM trial was temporarily paused in February 2019, briefly restarted, and then prematurely stopped in April 2019.

FDA officials said the study was paused at the recommendation of the data monitoring committee (DMC) because rates of safety events were different between patients and control subjects and operational errors called into question the accuracy of the data being reviewed. Ultimately, both the DMC and FDA recommended study suspension.

During the public hearing, TAVR pioneer Alain Cribier, MD, University of Rouen’s Charles Nicolle Hospital, Mont-Saint-Aignan, France, said the TriGuard 3 is of interest because it can be used with minimal need for manipulation and complete coverage of the cerebral vessels that is achieved by diverting rather than capturing debris. “The rapid and exponential growth of TAVR procedures demands safe TAVR interventions and the use of cerebral protection devices is a step in this direction.”

Others took a dim view. “Given that the Sentinel device has not demonstrated benefit on clinical outcomes, there is significant concern about similar devices, such as the TriGuard 3, providing clinical benefit,” Rita Redberg, MD, Sanket Dhruva, MD, and Robin Ji, University of California, San Francisco, wrote in a letter submitted to the panel.

Commenting further, they added: “With the results from the REFLECT II trial demonstrating no evidence for clinical outcome benefit in TAVR patients, and numerically higher rates for stroke risk, mortality, bleeding risk, and other dangerous adverse complications among those treated, it is concerning and dangerous for patient safety that the TriGUARD 3 cerebral embolic protection device is being considered for FDA 510(k) clearance.”

The FDA panel members reported no financial relationships.

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

A Food and Drug Administration advisory panel struggled to muster support for marketing clearance of the TriGuard 3 (Keystone Heart) device for use during transcatheter aortic valve replacement (TAVR).

The Circulatory Systems Devices Panel of the Medical Devices Advisory Committee took no vote when it met Aug. 3, but weighed evidence for a proposed indication for the device “to minimize the risk of cerebral damage by deflecting embolic debris away from the cerebral circulation” during TAVR.

“While this device may deflect some debris, the data would suggest it may also create issues,” said Keith B. Allen, MD, director of surgical research at the Mid America Heart & Lung Surgeons, Kansas City, Mo. “I am really concerned that our desire and the emotion that surrounds preventing stroke are not being supported by the data.”

TriGuard 3 received CE Mark in Europe in March 2020. It was submitted for 510(k) clearance and seeks to prove substantial equivalence to the predicate Sentinel device (Claret Medical), currently the only approved embolic protection device in the United States.

The device is designed to cover all three major aortic vessels (innominate, left carotid, and left subclavian arteries) and is delivered transfemorally through an 8F sheath, whereas the Sentinel is positioned within the branch vessels, doesn’t cover the left subclavian artery, and is introduced through the radial or brachial artery via a 6F sheath.

TriGuard 3 faced an uphill battle, however, after failing to meet the primary composite efficacy endpoint in the REFLECT phase 2 trial (P = .857), with numeric trends showing higher all-cause mortality or any stroke at 30 days (9.8% vs. 6.7%) than pooled control subjects without embolic protection.

Rates for other components of the endpoint also trended higher with the device: National Institutes of Stroke Stroke Scale score worsening 2-5 days after the procedure, cerebral ischemic lesions on MRI 2-5 days after the procedure, and total cerebral ischemic lesion volume.

The Sentinel device was approved in 2017 after it failed to meet its primary efficacy endpoint of new brain lesion volume on MRI, but death and stroke rates favored the device over control, the panel pointed out.

The sponsor provided additional analyses in the per treatment (PT) population, defined as those with complete three-vessel coverage in at least two of three procedural time points. Compared with pooled control subjects, most of the imaging endpoints favored the TriGuard 3 device, but clinical neurologic event rates continued to favor the control group.

“The data used to demonstrate efficacy are all based on the PT subpopulation of the whole population, and those have to be considered promissory data,” said John Hirshfeld, MD, emeritus professor, University of Pennsylvania, Philadelphia. “This is the group where everything went well and for us to decide that’s achievable in the general population is speculative.”
 

Safety data

The REFLECT trial did meet its primary safety endpoint, with a 30-day major adverse cardiovascular event rate of 15.9%, compared with a performance goal of 34.4% (P < .0001).

Although prespecified, panel members pushed back, saying that the performance goal was unacceptably high, with several members remarking they’d never heard of a trial adding 9% as a “fudge factor” to a 25% historic control rate to get to the 34% performance target.

Keystone health officials noted that REFLECT was not designed to demonstrate a significant difference in the rate of primary safety events, compared with control. Instead, its purpose was to demonstrate that TriGuard 3 did not increase the risk associated with a TAVR procedure.

The TriGuard 3 device was successfully placed and retrieved in 100% of patients, but complete coverage was not uniform, with 72% of 157 as-treated patients having complete three-vessel coverage post TAVR but 15% having no coverage.

Panel members also expressed concern over device interference during TAVR, which was reported in nearly 10% of all TriGuard patients.

The TriGuard 3 group had 11 major vascular complications, 2 directly related to the device, and 3 stage 3 acute kidney injuries, whereas neither complication occurred in the control group.

Throughout the 9-hour hearing, the panel wrestled with what was described as a highly select patient group and small patient numbers that made it difficult to interpret observed differences. The trial involved 157 TriGuard 3 patients (including 41 from the roll-in phase) and 119 control subjects pooled from phase 2 of the trial (n = 57) and from phase 1 using the early-stage TriGuard HDH device (n = 57).

Pieter Stella, MD, PhD, Utrecht (the Netherlands) Medical Center, also presented “real-world” evidence from 75 patients in the Netherlands using the latest iteration of the device available in Europe with updates to the crimper and additional training materials to prevent the device from torquing during delivery. No strokes were reported, one patient had a transient ischemic attack (TIA), and two patients had a dissection, which resolved without sequelae.

Ralph Brindis, MD, MPH, professor of medicine, University of California, San Francisco, countered that there were only three experienced operators from a single center and that the stroke incidence was physician reported, “not data we can really embrace.”

There was much debate over why enrollment in phase 2 of the RHYTHM trial was temporarily paused in February 2019, briefly restarted, and then prematurely stopped in April 2019.

FDA officials said the study was paused at the recommendation of the data monitoring committee (DMC) because rates of safety events were different between patients and control subjects and operational errors called into question the accuracy of the data being reviewed. Ultimately, both the DMC and FDA recommended study suspension.

During the public hearing, TAVR pioneer Alain Cribier, MD, University of Rouen’s Charles Nicolle Hospital, Mont-Saint-Aignan, France, said the TriGuard 3 is of interest because it can be used with minimal need for manipulation and complete coverage of the cerebral vessels that is achieved by diverting rather than capturing debris. “The rapid and exponential growth of TAVR procedures demands safe TAVR interventions and the use of cerebral protection devices is a step in this direction.”

Others took a dim view. “Given that the Sentinel device has not demonstrated benefit on clinical outcomes, there is significant concern about similar devices, such as the TriGuard 3, providing clinical benefit,” Rita Redberg, MD, Sanket Dhruva, MD, and Robin Ji, University of California, San Francisco, wrote in a letter submitted to the panel.

Commenting further, they added: “With the results from the REFLECT II trial demonstrating no evidence for clinical outcome benefit in TAVR patients, and numerically higher rates for stroke risk, mortality, bleeding risk, and other dangerous adverse complications among those treated, it is concerning and dangerous for patient safety that the TriGUARD 3 cerebral embolic protection device is being considered for FDA 510(k) clearance.”

The FDA panel members reported no financial relationships.

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

An incidental diagnosis of intracranial atherosclerotic stenosis in stroke-free individuals should trigger a thorough assessment of vascular health, according to the authors of a study identifying risk factors and vascular event risk in asymptomatic ICAS.

mr.suphachai praserdumrongchai/iStock/Getty Images Plus

That conclusion emerged from data collected on more than 1,000 stroke-free participants in NOMAS (Northern Manhattan Study), a trial that prospectively followed participants who underwent a brain magnetic resonance angiogram (MRA) during 2003-2008.

In ICAS patients with stenosis of at least 70%, even with aggressive medical therapy, the annual stroke recurrence rate is 10%-20% in those with occlusions and at least three or more vascular risk factors. This high rate of recurrent vascular events in patients with stroke caused by ICAS warrants greater focus on primary prevention and targeted interventions for stroke-free individuals at highest risk for ICAS-related events, the investigators concluded.
 

Identify high-risk ICAS

Using NOMAS data, the investigators, led by Jose Gutierrez, MD, MPH, tested the hypothesis that stroke-free subjects at high risk of stroke and vascular events could be identified through the presence of asymptomatic ICAS. NOMAS is an ongoing, population-based epidemiologic study among randomly selected people with home telephones living in northern Manhattan.

During 2003-2008, investigators invited participants who were at least 50 years old, stroke free, and without contraindications to undergo brain MRA. The 1,211 study members were followed annually via telephone and in-person adjudication of events. A control group of 79 patients with no MRA was also identified with similar rates of hypertension, diabetes, hypercholesterolemia and current smoking.

Mean age was about 71 years (59% female, 65% Hispanic, 45% any stenosis). At the time of MRA, 78% had hypertension, 25% had diabetes, 81% had hypercholesterolemia, and 11% were current smokers.

Researchers rated stenoses in 11 brain arteries as 0, with no stenosis; 1, with less than 50% stenosis or luminal irregularities; 2, 50%-69% stenosis; and 3, at least 70% stenosis or flow gap. Outcomes included vascular death, myocardial infarction, ischemic stroke, cardioembolic stroke, intracranial artery disease stroke (which combined intracranial small and large artery disease strokes), and any vascular events (defined as a composite of vascular death, any stroke, or MI).
 

Greater stenosis denotes higher risk

Analysis found ICAS to be associated with older age (odds ratio, 1.02 per year; 95% confidence interval, 1.01-1.04), hypertension duration (OR, 1.01 per year; 95% CI, 1.00-1.02), higher number of glucose-lowering drugs (OR, 1.64 per each medication; 95% CI, 1.24-2.15), and HDL cholesterol(OR, 0.96 per mg/dL; 95% CI, 0.92-0.99). Event risk was greater among participants with ICAS of at least 70% (5.5% annual risk of vascular events; HR, 2.1; 95% CI, 1.4-3.2; compared with those with no ICAS), the investigators reported in the Journal of the American College of Cardiology.

Furthermore, 80% of incident strokes initially classified as small artery disease occurred among individuals with evidence of any degree of ICAS at their baseline MRI, the investigators noted. They found also that individuals with ICAS who had a primary care physician at the time of their initial MRI had a lower risk of events. Frequent primary care visits, they observed, might imply greater control of risk factors and other unmeasured confounders, such as health literacy, health care trust, access, and availability.
 

Incidental ICAS should trigger vascular assessment

An incidental diagnosis of ICAS in stroke-free subjects should trigger a thorough assessment of vascular health, the investigators concluded. They commented also that prophylaxis of first-ever stroke at this asymptomatic stage “may magnify the societal benefits of vascular prevention and decrease stroke-related disability and vascular death in our communities.”

“The big gap in our knowledge,” Tanya N. Turan, MD, professor of neurology at Medical University of South Carolina, Charleston, wrote in an accompanying editorial “is understanding the pathophysiological triggers for an asymptomatic stenosis to become a high-risk symptomatic stenosis. Until that question is answered, screening for asymptomatic ICAS is unlikely to change management among patients with known vascular risk factors.” In an interview, she observed further that “MRI plaque imaging could be a useful research tool to see if certain plaque features in an asymptomatic lesion are high risk for causing stroke. If that were proven, then it would make more sense to screen for ICAS and develop specific therapeutic strategies targeting high-risk asymptomatic plaque.”
 

Focus on recurrent stroke misplaced

Dr. Gutierrez said in an interview: “In the stroke world, most of what we do focuses on preventing recurrent stroke. Nonetheless, three-fourths of strokes in this country are new strokes, so to me it doesn’t make much sense to spend most of our efforts and attention to prevent the smallest fractions of strokes that occur in our society.”

He stressed that “the first immediate application of our results is that if people having a brain MRA for other reasons are found to have incidental, and therefore asymptomatic, ICAS, then they should be aggressively treated for vascular risk factors.” Secondly, “we hope to identify the patients at the highest risk of prevalent ICAS before they have a stroke. Among them, a brain MRI/MRA evaluating the phenotype would determine how aggressively to treat LDL.”

Dr. Gutierrez, professor of neurology at Columbia University Irving Medical Center, New York, noted that educating patients of their underlying high risk of events may have the effect of engaging them more in their own care. “There is evidence that actually showing people scans increases compliance and health literacy. It’s not yet standard of care, but we hope our future projects will help advance the field in the primary prevention direction,” he said.

This work was supported by the National Institutes of Health. The authors reported that they had no relevant financial disclosures.

An incidental diagnosis of intracranial atherosclerotic stenosis in stroke-free individuals should trigger a thorough assessment of vascular health, according to the authors of a study identifying risk factors and vascular event risk in asymptomatic ICAS.

mr.suphachai praserdumrongchai/iStock/Getty Images Plus

That conclusion emerged from data collected on more than 1,000 stroke-free participants in NOMAS (Northern Manhattan Study), a trial that prospectively followed participants who underwent a brain magnetic resonance angiogram (MRA) during 2003-2008.

In ICAS patients with stenosis of at least 70%, even with aggressive medical therapy, the annual stroke recurrence rate is 10%-20% in those with occlusions and at least three or more vascular risk factors. This high rate of recurrent vascular events in patients with stroke caused by ICAS warrants greater focus on primary prevention and targeted interventions for stroke-free individuals at highest risk for ICAS-related events, the investigators concluded.
 

Identify high-risk ICAS

Using NOMAS data, the investigators, led by Jose Gutierrez, MD, MPH, tested the hypothesis that stroke-free subjects at high risk of stroke and vascular events could be identified through the presence of asymptomatic ICAS. NOMAS is an ongoing, population-based epidemiologic study among randomly selected people with home telephones living in northern Manhattan.

During 2003-2008, investigators invited participants who were at least 50 years old, stroke free, and without contraindications to undergo brain MRA. The 1,211 study members were followed annually via telephone and in-person adjudication of events. A control group of 79 patients with no MRA was also identified with similar rates of hypertension, diabetes, hypercholesterolemia and current smoking.

Mean age was about 71 years (59% female, 65% Hispanic, 45% any stenosis). At the time of MRA, 78% had hypertension, 25% had diabetes, 81% had hypercholesterolemia, and 11% were current smokers.

Researchers rated stenoses in 11 brain arteries as 0, with no stenosis; 1, with less than 50% stenosis or luminal irregularities; 2, 50%-69% stenosis; and 3, at least 70% stenosis or flow gap. Outcomes included vascular death, myocardial infarction, ischemic stroke, cardioembolic stroke, intracranial artery disease stroke (which combined intracranial small and large artery disease strokes), and any vascular events (defined as a composite of vascular death, any stroke, or MI).
 

Greater stenosis denotes higher risk

Analysis found ICAS to be associated with older age (odds ratio, 1.02 per year; 95% confidence interval, 1.01-1.04), hypertension duration (OR, 1.01 per year; 95% CI, 1.00-1.02), higher number of glucose-lowering drugs (OR, 1.64 per each medication; 95% CI, 1.24-2.15), and HDL cholesterol(OR, 0.96 per mg/dL; 95% CI, 0.92-0.99). Event risk was greater among participants with ICAS of at least 70% (5.5% annual risk of vascular events; HR, 2.1; 95% CI, 1.4-3.2; compared with those with no ICAS), the investigators reported in the Journal of the American College of Cardiology.

Furthermore, 80% of incident strokes initially classified as small artery disease occurred among individuals with evidence of any degree of ICAS at their baseline MRI, the investigators noted. They found also that individuals with ICAS who had a primary care physician at the time of their initial MRI had a lower risk of events. Frequent primary care visits, they observed, might imply greater control of risk factors and other unmeasured confounders, such as health literacy, health care trust, access, and availability.
 

Incidental ICAS should trigger vascular assessment

An incidental diagnosis of ICAS in stroke-free subjects should trigger a thorough assessment of vascular health, the investigators concluded. They commented also that prophylaxis of first-ever stroke at this asymptomatic stage “may magnify the societal benefits of vascular prevention and decrease stroke-related disability and vascular death in our communities.”

“The big gap in our knowledge,” Tanya N. Turan, MD, professor of neurology at Medical University of South Carolina, Charleston, wrote in an accompanying editorial “is understanding the pathophysiological triggers for an asymptomatic stenosis to become a high-risk symptomatic stenosis. Until that question is answered, screening for asymptomatic ICAS is unlikely to change management among patients with known vascular risk factors.” In an interview, she observed further that “MRI plaque imaging could be a useful research tool to see if certain plaque features in an asymptomatic lesion are high risk for causing stroke. If that were proven, then it would make more sense to screen for ICAS and develop specific therapeutic strategies targeting high-risk asymptomatic plaque.”
 

Focus on recurrent stroke misplaced

Dr. Gutierrez said in an interview: “In the stroke world, most of what we do focuses on preventing recurrent stroke. Nonetheless, three-fourths of strokes in this country are new strokes, so to me it doesn’t make much sense to spend most of our efforts and attention to prevent the smallest fractions of strokes that occur in our society.”

He stressed that “the first immediate application of our results is that if people having a brain MRA for other reasons are found to have incidental, and therefore asymptomatic, ICAS, then they should be aggressively treated for vascular risk factors.” Secondly, “we hope to identify the patients at the highest risk of prevalent ICAS before they have a stroke. Among them, a brain MRI/MRA evaluating the phenotype would determine how aggressively to treat LDL.”

Dr. Gutierrez, professor of neurology at Columbia University Irving Medical Center, New York, noted that educating patients of their underlying high risk of events may have the effect of engaging them more in their own care. “There is evidence that actually showing people scans increases compliance and health literacy. It’s not yet standard of care, but we hope our future projects will help advance the field in the primary prevention direction,” he said.

This work was supported by the National Institutes of Health. The authors reported that they had no relevant financial disclosures.

An incidental diagnosis of intracranial atherosclerotic stenosis in stroke-free individuals should trigger a thorough assessment of vascular health, according to the authors of a study identifying risk factors and vascular event risk in asymptomatic ICAS.

mr.suphachai praserdumrongchai/iStock/Getty Images Plus

That conclusion emerged from data collected on more than 1,000 stroke-free participants in NOMAS (Northern Manhattan Study), a trial that prospectively followed participants who underwent a brain magnetic resonance angiogram (MRA) during 2003-2008.

In ICAS patients with stenosis of at least 70%, even with aggressive medical therapy, the annual stroke recurrence rate is 10%-20% in those with occlusions and at least three or more vascular risk factors. This high rate of recurrent vascular events in patients with stroke caused by ICAS warrants greater focus on primary prevention and targeted interventions for stroke-free individuals at highest risk for ICAS-related events, the investigators concluded.
 

Identify high-risk ICAS

Using NOMAS data, the investigators, led by Jose Gutierrez, MD, MPH, tested the hypothesis that stroke-free subjects at high risk of stroke and vascular events could be identified through the presence of asymptomatic ICAS. NOMAS is an ongoing, population-based epidemiologic study among randomly selected people with home telephones living in northern Manhattan.

During 2003-2008, investigators invited participants who were at least 50 years old, stroke free, and without contraindications to undergo brain MRA. The 1,211 study members were followed annually via telephone and in-person adjudication of events. A control group of 79 patients with no MRA was also identified with similar rates of hypertension, diabetes, hypercholesterolemia and current smoking.

Mean age was about 71 years (59% female, 65% Hispanic, 45% any stenosis). At the time of MRA, 78% had hypertension, 25% had diabetes, 81% had hypercholesterolemia, and 11% were current smokers.

Researchers rated stenoses in 11 brain arteries as 0, with no stenosis; 1, with less than 50% stenosis or luminal irregularities; 2, 50%-69% stenosis; and 3, at least 70% stenosis or flow gap. Outcomes included vascular death, myocardial infarction, ischemic stroke, cardioembolic stroke, intracranial artery disease stroke (which combined intracranial small and large artery disease strokes), and any vascular events (defined as a composite of vascular death, any stroke, or MI).
 

Greater stenosis denotes higher risk

Analysis found ICAS to be associated with older age (odds ratio, 1.02 per year; 95% confidence interval, 1.01-1.04), hypertension duration (OR, 1.01 per year; 95% CI, 1.00-1.02), higher number of glucose-lowering drugs (OR, 1.64 per each medication; 95% CI, 1.24-2.15), and HDL cholesterol(OR, 0.96 per mg/dL; 95% CI, 0.92-0.99). Event risk was greater among participants with ICAS of at least 70% (5.5% annual risk of vascular events; HR, 2.1; 95% CI, 1.4-3.2; compared with those with no ICAS), the investigators reported in the Journal of the American College of Cardiology.

Furthermore, 80% of incident strokes initially classified as small artery disease occurred among individuals with evidence of any degree of ICAS at their baseline MRI, the investigators noted. They found also that individuals with ICAS who had a primary care physician at the time of their initial MRI had a lower risk of events. Frequent primary care visits, they observed, might imply greater control of risk factors and other unmeasured confounders, such as health literacy, health care trust, access, and availability.
 

Incidental ICAS should trigger vascular assessment

An incidental diagnosis of ICAS in stroke-free subjects should trigger a thorough assessment of vascular health, the investigators concluded. They commented also that prophylaxis of first-ever stroke at this asymptomatic stage “may magnify the societal benefits of vascular prevention and decrease stroke-related disability and vascular death in our communities.”

“The big gap in our knowledge,” Tanya N. Turan, MD, professor of neurology at Medical University of South Carolina, Charleston, wrote in an accompanying editorial “is understanding the pathophysiological triggers for an asymptomatic stenosis to become a high-risk symptomatic stenosis. Until that question is answered, screening for asymptomatic ICAS is unlikely to change management among patients with known vascular risk factors.” In an interview, she observed further that “MRI plaque imaging could be a useful research tool to see if certain plaque features in an asymptomatic lesion are high risk for causing stroke. If that were proven, then it would make more sense to screen for ICAS and develop specific therapeutic strategies targeting high-risk asymptomatic plaque.”
 

Focus on recurrent stroke misplaced

Dr. Gutierrez said in an interview: “In the stroke world, most of what we do focuses on preventing recurrent stroke. Nonetheless, three-fourths of strokes in this country are new strokes, so to me it doesn’t make much sense to spend most of our efforts and attention to prevent the smallest fractions of strokes that occur in our society.”

He stressed that “the first immediate application of our results is that if people having a brain MRA for other reasons are found to have incidental, and therefore asymptomatic, ICAS, then they should be aggressively treated for vascular risk factors.” Secondly, “we hope to identify the patients at the highest risk of prevalent ICAS before they have a stroke. Among them, a brain MRI/MRA evaluating the phenotype would determine how aggressively to treat LDL.”

Dr. Gutierrez, professor of neurology at Columbia University Irving Medical Center, New York, noted that educating patients of their underlying high risk of events may have the effect of engaging them more in their own care. “There is evidence that actually showing people scans increases compliance and health literacy. It’s not yet standard of care, but we hope our future projects will help advance the field in the primary prevention direction,” he said.

This work was supported by the National Institutes of Health. The authors reported that they had no relevant financial disclosures.

Catheter ablation has been around a lot longer for ventricular arrhythmia than for atrial fibrillation, but far less is settled about what antithrombotic therapy should follow ventricular ablations, as there have been no big, randomized trials for guidance.

But the evidence base grew stronger this week, and it favors postprocedure treatment with a direct oral anticoagulant (DOAC) over antiplatelet therapy with aspirin for patients undergoing radiofrequency (RF) ablation to treat left ventricular (LV) arrhythmias.

The 30-day risk for ischemic stroke or transient ischemia attack (TIA) was sharply higher for patients who took daily aspirin after RF ablation for ventricular tachycardia (VT) or premature ventricular contractions (PVC) in a multicenter randomized trial.

Those of its 246 patients who received aspirin were also far more likely to show asymptomatic lesions on cerebral MRI scans performed both 24 hours and 30 days after the procedure.

The findings show the importance of DOAC therapy after ventricular ablation procedures, a setting for which there are no evidence-based guidelines, “to mitigate the risk of systemic thromboembolic events,” said Dhanunjaya Lakkireddy, MD, Kansas City Heart Rhythm Institute, Overland Park. He spoke at a media presentation on the trial, called STROKE-VT, during the Heart Rhythm Society 2021 Scientific Sessions, held virtually and on-site in Boston.

The risk for stroke and TIA went up in association with several procedural issues, including some that operators might be able to change in order to reach for better outcomes, Dr. Lakkireddy observed.

“Prolonged radiofrequency ablation times, especially in those with low left ventricle ejection fractions, are definitely higher risk,” as are procedures that involved the retrograde transaortic approach for advancing the ablation catheter, rather than a trans-septal approach.

The retrograde transaortic approach should be avoided in such procedures, “whenever it can be avoided,” said Dr. Lakkireddy, who formally presented STROKE-VT at the HRS sessions and is lead author on its report published about the same time in JACC: Clinical Electrophysiology.

The trial has limitations, but “it’s a very important study, and I think that this could become our standard of care for managing anticoagulation after VT and PVC left-sided ablations,” Mina K. Chung, MD, Cleveland Clinic, said as an invited discussant after Dr. Lakkireddy’s presentation.

How patients are treated with antithrombotics after ventricular ablations can vary widely, sometimes based on the operator’s “subjective feeling of how extensive the ablation is,” Christine M. Albert, MD, MPH, Cedars-Sinai Medical Center, Los Angeles, not involved in the study, said during the STROKE-VT media briefing.

That’s consistent with the guidelines, which propose oral anticoagulation therapy after more extensive ventricular ablations and antiplatelets when the ablation is more limited – based more on consensus than firm evidence – as described by Jeffrey R. Winterfield, MD, Medical University of South Carolina, Charleston, and Usha Tedrow, MD, MSc, Brigham and Women’s Hospital, Boston, in an accompanying editorial.

“This is really the first randomized trial data, that I know of, that we have on this. So I do think it will be guideline-influencing,” Dr. Albert said.

“This should change practice,” agreed Jonathan P. Piccini, MD, MHS, Duke University, Durham, N.C., also not part of STROKE-VT. “A lot of evidence in the trial is consistent and provides a compelling story, not to mention that, in my opinion, the study probably underestimates the value of DOACs,” he told this news organization.

That’s because patients assigned to DOACs had far longer ablation times, “so their risk was even greater than in the aspirin arm,” Dr. Piccini said. Ablation times averaged 2,095 seconds in the DOAC group, compared with only 1,708 seconds in the aspirin group, probably because the preponderance of VT over PVC ablations for those getting a DOAC was even greater in the aspirin group.

Of the 246 patients assigned to either aspirin or a DOAC, usually a factor Xa inhibitor, 75% had undergone VT ablation and the remainder ablation for PVCs. Their mean age was 60 years and only 18% were women. None had experienced a cerebrovascular event in the previous 3 months.

The 30-day odds ratio for TIA or ischemic stroke in patients who received aspirin, compared with a DOAC, was 12.6 (95% confidence interval, 4.10-39.11; P < .001).

The corresponding OR for asymptomatic cerebral lesions by MRI at 24 hours was 2.15 (95% CI, 1.02-4.54; P = .04) and at 30 days was 3.48 (95% CI, 1.38-8.80; P = .008).

The rate of stroke or TIA was similar in patients who underwent ablation for VT and for PVCs (14% vs. 16%, respectively; P = .70). There were fewer asymptomatic cerebrovascular events by MRI at 24 hours for those undergoing VT ablations (14.7% and 25.8%, respectively; P = .046); but difference between rates attenuated by 30 days (11.4% and 14.5%, respectively; P = .52).

The OR for TIA or stroke associated with the retrograde transaortic approach, performed in about 40% of the patients, compared with the trans-septal approach in the remainder was 2.60 (95% CI, 1.06-6.37; P = .04).

“The study tells us it’s safe and indeed preferable to anticoagulate after an ablation procedure. But the more important finding, perhaps, wasn’t the one related to the core hypothesis. And that was the effect of retrograde access,” Paul A. Friedman, MD, Mayo Clinic, Rochester, Minn., said as an invited discussant after Dr. Lakkireddy’s formal presentation of the trial.

Whether a ventricular ablation is performed using the retrograde transaortic or trans-septal approach often depends on the location of the ablation targets in the left ventricle. But in some cases it’s a matter of operator preference, Dr. Piccini observed.

“There are some situations where, really, it is better to do retrograde aortic, and there are some cases that are better to do trans-septal. But now there’s going to be a higher burden of proof,” he said. Given the findings of STROKE-VT, operators may need to consider that a ventricular ablation procedure that can be done by the trans-septal route perhaps ought to be consistently done that way.

Dr. Lakkireddy discloses financial relationships with Boston Scientific, Biosense Webster, Janssen Pharmaceuticals, and more. Dr. Chung had “nothing relevant to disclose.” Dr. Piccini discloses receiving honoraria or speaking or consulting fees from Sanofi, Abbott, ARCA Biopharma, Medtronic, Philips, Biotronik, Allergan, LivaNova, and Myokardia; and research in conjunction with Bayer Healthcare, Abbott, Boston Scientific, and Philips. Dr. Friedman discloses conducting research in conjunction with Medtronic and Abbott; holding intellectual property rights with AliveCor, Inference, Medicool, Eko, and Anumana; and receiving honoraria or speaking or consulting fees from Boston Scientific. Dr. Winterfield and Dr. Tedrow had no disclosures.

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

Catheter ablation has been around a lot longer for ventricular arrhythmia than for atrial fibrillation, but far less is settled about what antithrombotic therapy should follow ventricular ablations, as there have been no big, randomized trials for guidance.

But the evidence base grew stronger this week, and it favors postprocedure treatment with a direct oral anticoagulant (DOAC) over antiplatelet therapy with aspirin for patients undergoing radiofrequency (RF) ablation to treat left ventricular (LV) arrhythmias.

The 30-day risk for ischemic stroke or transient ischemia attack (TIA) was sharply higher for patients who took daily aspirin after RF ablation for ventricular tachycardia (VT) or premature ventricular contractions (PVC) in a multicenter randomized trial.

Those of its 246 patients who received aspirin were also far more likely to show asymptomatic lesions on cerebral MRI scans performed both 24 hours and 30 days after the procedure.

The findings show the importance of DOAC therapy after ventricular ablation procedures, a setting for which there are no evidence-based guidelines, “to mitigate the risk of systemic thromboembolic events,” said Dhanunjaya Lakkireddy, MD, Kansas City Heart Rhythm Institute, Overland Park. He spoke at a media presentation on the trial, called STROKE-VT, during the Heart Rhythm Society 2021 Scientific Sessions, held virtually and on-site in Boston.

The risk for stroke and TIA went up in association with several procedural issues, including some that operators might be able to change in order to reach for better outcomes, Dr. Lakkireddy observed.

“Prolonged radiofrequency ablation times, especially in those with low left ventricle ejection fractions, are definitely higher risk,” as are procedures that involved the retrograde transaortic approach for advancing the ablation catheter, rather than a trans-septal approach.

The retrograde transaortic approach should be avoided in such procedures, “whenever it can be avoided,” said Dr. Lakkireddy, who formally presented STROKE-VT at the HRS sessions and is lead author on its report published about the same time in JACC: Clinical Electrophysiology.

The trial has limitations, but “it’s a very important study, and I think that this could become our standard of care for managing anticoagulation after VT and PVC left-sided ablations,” Mina K. Chung, MD, Cleveland Clinic, said as an invited discussant after Dr. Lakkireddy’s presentation.

How patients are treated with antithrombotics after ventricular ablations can vary widely, sometimes based on the operator’s “subjective feeling of how extensive the ablation is,” Christine M. Albert, MD, MPH, Cedars-Sinai Medical Center, Los Angeles, not involved in the study, said during the STROKE-VT media briefing.

That’s consistent with the guidelines, which propose oral anticoagulation therapy after more extensive ventricular ablations and antiplatelets when the ablation is more limited – based more on consensus than firm evidence – as described by Jeffrey R. Winterfield, MD, Medical University of South Carolina, Charleston, and Usha Tedrow, MD, MSc, Brigham and Women’s Hospital, Boston, in an accompanying editorial.

“This is really the first randomized trial data, that I know of, that we have on this. So I do think it will be guideline-influencing,” Dr. Albert said.

“This should change practice,” agreed Jonathan P. Piccini, MD, MHS, Duke University, Durham, N.C., also not part of STROKE-VT. “A lot of evidence in the trial is consistent and provides a compelling story, not to mention that, in my opinion, the study probably underestimates the value of DOACs,” he told this news organization.

That’s because patients assigned to DOACs had far longer ablation times, “so their risk was even greater than in the aspirin arm,” Dr. Piccini said. Ablation times averaged 2,095 seconds in the DOAC group, compared with only 1,708 seconds in the aspirin group, probably because the preponderance of VT over PVC ablations for those getting a DOAC was even greater in the aspirin group.

Of the 246 patients assigned to either aspirin or a DOAC, usually a factor Xa inhibitor, 75% had undergone VT ablation and the remainder ablation for PVCs. Their mean age was 60 years and only 18% were women. None had experienced a cerebrovascular event in the previous 3 months.

The 30-day odds ratio for TIA or ischemic stroke in patients who received aspirin, compared with a DOAC, was 12.6 (95% confidence interval, 4.10-39.11; P < .001).

The corresponding OR for asymptomatic cerebral lesions by MRI at 24 hours was 2.15 (95% CI, 1.02-4.54; P = .04) and at 30 days was 3.48 (95% CI, 1.38-8.80; P = .008).

The rate of stroke or TIA was similar in patients who underwent ablation for VT and for PVCs (14% vs. 16%, respectively; P = .70). There were fewer asymptomatic cerebrovascular events by MRI at 24 hours for those undergoing VT ablations (14.7% and 25.8%, respectively; P = .046); but difference between rates attenuated by 30 days (11.4% and 14.5%, respectively; P = .52).

The OR for TIA or stroke associated with the retrograde transaortic approach, performed in about 40% of the patients, compared with the trans-septal approach in the remainder was 2.60 (95% CI, 1.06-6.37; P = .04).

“The study tells us it’s safe and indeed preferable to anticoagulate after an ablation procedure. But the more important finding, perhaps, wasn’t the one related to the core hypothesis. And that was the effect of retrograde access,” Paul A. Friedman, MD, Mayo Clinic, Rochester, Minn., said as an invited discussant after Dr. Lakkireddy’s formal presentation of the trial.

Whether a ventricular ablation is performed using the retrograde transaortic or trans-septal approach often depends on the location of the ablation targets in the left ventricle. But in some cases it’s a matter of operator preference, Dr. Piccini observed.

“There are some situations where, really, it is better to do retrograde aortic, and there are some cases that are better to do trans-septal. But now there’s going to be a higher burden of proof,” he said. Given the findings of STROKE-VT, operators may need to consider that a ventricular ablation procedure that can be done by the trans-septal route perhaps ought to be consistently done that way.

Dr. Lakkireddy discloses financial relationships with Boston Scientific, Biosense Webster, Janssen Pharmaceuticals, and more. Dr. Chung had “nothing relevant to disclose.” Dr. Piccini discloses receiving honoraria or speaking or consulting fees from Sanofi, Abbott, ARCA Biopharma, Medtronic, Philips, Biotronik, Allergan, LivaNova, and Myokardia; and research in conjunction with Bayer Healthcare, Abbott, Boston Scientific, and Philips. Dr. Friedman discloses conducting research in conjunction with Medtronic and Abbott; holding intellectual property rights with AliveCor, Inference, Medicool, Eko, and Anumana; and receiving honoraria or speaking or consulting fees from Boston Scientific. Dr. Winterfield and Dr. Tedrow had no disclosures.

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

Catheter ablation has been around a lot longer for ventricular arrhythmia than for atrial fibrillation, but far less is settled about what antithrombotic therapy should follow ventricular ablations, as there have been no big, randomized trials for guidance.

But the evidence base grew stronger this week, and it favors postprocedure treatment with a direct oral anticoagulant (DOAC) over antiplatelet therapy with aspirin for patients undergoing radiofrequency (RF) ablation to treat left ventricular (LV) arrhythmias.

The 30-day risk for ischemic stroke or transient ischemia attack (TIA) was sharply higher for patients who took daily aspirin after RF ablation for ventricular tachycardia (VT) or premature ventricular contractions (PVC) in a multicenter randomized trial.

Those of its 246 patients who received aspirin were also far more likely to show asymptomatic lesions on cerebral MRI scans performed both 24 hours and 30 days after the procedure.

The findings show the importance of DOAC therapy after ventricular ablation procedures, a setting for which there are no evidence-based guidelines, “to mitigate the risk of systemic thromboembolic events,” said Dhanunjaya Lakkireddy, MD, Kansas City Heart Rhythm Institute, Overland Park. He spoke at a media presentation on the trial, called STROKE-VT, during the Heart Rhythm Society 2021 Scientific Sessions, held virtually and on-site in Boston.

The risk for stroke and TIA went up in association with several procedural issues, including some that operators might be able to change in order to reach for better outcomes, Dr. Lakkireddy observed.

“Prolonged radiofrequency ablation times, especially in those with low left ventricle ejection fractions, are definitely higher risk,” as are procedures that involved the retrograde transaortic approach for advancing the ablation catheter, rather than a trans-septal approach.

The retrograde transaortic approach should be avoided in such procedures, “whenever it can be avoided,” said Dr. Lakkireddy, who formally presented STROKE-VT at the HRS sessions and is lead author on its report published about the same time in JACC: Clinical Electrophysiology.

The trial has limitations, but “it’s a very important study, and I think that this could become our standard of care for managing anticoagulation after VT and PVC left-sided ablations,” Mina K. Chung, MD, Cleveland Clinic, said as an invited discussant after Dr. Lakkireddy’s presentation.

How patients are treated with antithrombotics after ventricular ablations can vary widely, sometimes based on the operator’s “subjective feeling of how extensive the ablation is,” Christine M. Albert, MD, MPH, Cedars-Sinai Medical Center, Los Angeles, not involved in the study, said during the STROKE-VT media briefing.

That’s consistent with the guidelines, which propose oral anticoagulation therapy after more extensive ventricular ablations and antiplatelets when the ablation is more limited – based more on consensus than firm evidence – as described by Jeffrey R. Winterfield, MD, Medical University of South Carolina, Charleston, and Usha Tedrow, MD, MSc, Brigham and Women’s Hospital, Boston, in an accompanying editorial.

“This is really the first randomized trial data, that I know of, that we have on this. So I do think it will be guideline-influencing,” Dr. Albert said.

“This should change practice,” agreed Jonathan P. Piccini, MD, MHS, Duke University, Durham, N.C., also not part of STROKE-VT. “A lot of evidence in the trial is consistent and provides a compelling story, not to mention that, in my opinion, the study probably underestimates the value of DOACs,” he told this news organization.

That’s because patients assigned to DOACs had far longer ablation times, “so their risk was even greater than in the aspirin arm,” Dr. Piccini said. Ablation times averaged 2,095 seconds in the DOAC group, compared with only 1,708 seconds in the aspirin group, probably because the preponderance of VT over PVC ablations for those getting a DOAC was even greater in the aspirin group.

Of the 246 patients assigned to either aspirin or a DOAC, usually a factor Xa inhibitor, 75% had undergone VT ablation and the remainder ablation for PVCs. Their mean age was 60 years and only 18% were women. None had experienced a cerebrovascular event in the previous 3 months.

The 30-day odds ratio for TIA or ischemic stroke in patients who received aspirin, compared with a DOAC, was 12.6 (95% confidence interval, 4.10-39.11; P < .001).

The corresponding OR for asymptomatic cerebral lesions by MRI at 24 hours was 2.15 (95% CI, 1.02-4.54; P = .04) and at 30 days was 3.48 (95% CI, 1.38-8.80; P = .008).

The rate of stroke or TIA was similar in patients who underwent ablation for VT and for PVCs (14% vs. 16%, respectively; P = .70). There were fewer asymptomatic cerebrovascular events by MRI at 24 hours for those undergoing VT ablations (14.7% and 25.8%, respectively; P = .046); but difference between rates attenuated by 30 days (11.4% and 14.5%, respectively; P = .52).

The OR for TIA or stroke associated with the retrograde transaortic approach, performed in about 40% of the patients, compared with the trans-septal approach in the remainder was 2.60 (95% CI, 1.06-6.37; P = .04).

“The study tells us it’s safe and indeed preferable to anticoagulate after an ablation procedure. But the more important finding, perhaps, wasn’t the one related to the core hypothesis. And that was the effect of retrograde access,” Paul A. Friedman, MD, Mayo Clinic, Rochester, Minn., said as an invited discussant after Dr. Lakkireddy’s formal presentation of the trial.

Whether a ventricular ablation is performed using the retrograde transaortic or trans-septal approach often depends on the location of the ablation targets in the left ventricle. But in some cases it’s a matter of operator preference, Dr. Piccini observed.

“There are some situations where, really, it is better to do retrograde aortic, and there are some cases that are better to do trans-septal. But now there’s going to be a higher burden of proof,” he said. Given the findings of STROKE-VT, operators may need to consider that a ventricular ablation procedure that can be done by the trans-septal route perhaps ought to be consistently done that way.

Dr. Lakkireddy discloses financial relationships with Boston Scientific, Biosense Webster, Janssen Pharmaceuticals, and more. Dr. Chung had “nothing relevant to disclose.” Dr. Piccini discloses receiving honoraria or speaking or consulting fees from Sanofi, Abbott, ARCA Biopharma, Medtronic, Philips, Biotronik, Allergan, LivaNova, and Myokardia; and research in conjunction with Bayer Healthcare, Abbott, Boston Scientific, and Philips. Dr. Friedman discloses conducting research in conjunction with Medtronic and Abbott; holding intellectual property rights with AliveCor, Inference, Medicool, Eko, and Anumana; and receiving honoraria or speaking or consulting fees from Boston Scientific. Dr. Winterfield and Dr. Tedrow had no disclosures.

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

Medicare Part D spending for oral anticoagulants has risen by almost 1,600% since 2011, while the number of users has increased by just 95%, according to a new study.

In 2011, the year after the first direct oral anticoagulant (DOACs) was approved, Medicare Part D spent $0.44 billion on all oral anticoagulants. By 2019, when there a total of four DOACs on the market, spending was $7.38 billion, an increase of 1,577%, Aaron Troy, MD, MPH, and Timothy S. Anderson, MD, MAS, said in JAMA Health Forum.

[email protected]

Medicare Part D spending for oral anticoagulants has risen by almost 1,600% since 2011, while the number of users has increased by just 95%, according to a new study.

In 2011, the year after the first direct oral anticoagulant (DOACs) was approved, Medicare Part D spent $0.44 billion on all oral anticoagulants. By 2019, when there a total of four DOACs on the market, spending was $7.38 billion, an increase of 1,577%, Aaron Troy, MD, MPH, and Timothy S. Anderson, MD, MAS, said in JAMA Health Forum.

[email protected]

Medicare Part D spending for oral anticoagulants has risen by almost 1,600% since 2011, while the number of users has increased by just 95%, according to a new study.

In 2011, the year after the first direct oral anticoagulant (DOACs) was approved, Medicare Part D spent $0.44 billion on all oral anticoagulants. By 2019, when there a total of four DOACs on the market, spending was $7.38 billion, an increase of 1,577%, Aaron Troy, MD, MPH, and Timothy S. Anderson, MD, MAS, said in JAMA Health Forum.

[email protected]

People age 40 and younger living with HIV have a higher risk for heart disease than even their over-40 peers living with HIV – and that risk was 54% higher than the general public.

And this was among people without traditional heart disease risks, such as smoking and obesity.

“What’s surprising is that not only do we see that, yes, they do have increased risk, but this is after controlling for all of that – which means the mechanism underlying this risk,” said Tiffany Gooden, MPH and a PhD candidate at the University of Birmingham, England, who presented the data at the 11th International AIDS Society Conference on HIV Science (IAS 2021).

“If we’re using a non–HIV-validated assessment tool, you should always know that there could be a risk that you are under-recognizing,” she added.

Right now, there’s not a lot to aid clinicians in ferreting out this increased risk. Traditional cardiovascular risk assessment tools, like Framingham risk scores and atherosclerotic cardiovascular disease risk score from the American College of Cardiology, have been found to overlook the real risk of cardiovascular disease in people living with HIV. Plus, most guidelines, including those from the British HIV Medical Association and the American College of Cardiology, primarily focus screening on people 40 or older.

Ms. Gooden’s study drew data from The Health Improvement Network (THIN) database, which combines data from 800 primary care practices in the United Kingdom. Looking at data between January 2000 and January 2020, the investigators compared each person living with HIV with four peers not living with HIV, matched for age, gender, and practice. In total, 9,233 people living with HIV and 35,721 people without HIV were included in the analysis. Median age of participants was 41 years in people living with HIV and 40.4 years in people without HIV. About 35% of participants in both arms were women, and a greater proportion of participants living with HIV were Black, accounting for 22.5% of people living with HIV, versus 3.8% of the general population. Fewer people living with HIV were overweight or obese compared to people without HIV.

Researchers then tracked participants over time to identify the incidence of heart attack, stroke, peripheral vascular disease, and heart failure, as well as common risk factors for heart problems, such as high blood pressure, type 2 diabetes, chronic kidney disease, atrial fibrillation, and use of a lipid-lowering drug such as a statin.

The investigators then sectioned the data on heart disease risk by decade – 2000-2009 and 2010-2019 – in order to separate the potential impact of antiretroviral treatment (ART) drugs, from early combinations that have been associated with cardiovascular disease, to current drugs that are less likely to have that effect.

Overall risk for any kind of cardiovascular disease was 54% higher among people living with HIV of any age, compared to their age- and risk-matched peers. And when they broke the data down by age, they found that people younger than 40 had nearly twice the risk for any heart disease as their HIV-negative peers, which was a numerically higher risk than for people older than 40 – though not significantly so.

People living with HIV also had a 49% increased risk for stroke and a 59% increased risk for ischemic heart disease but no increased risk for peripheral vascular disease, heart failure, or heart attack. But the confidence intervals here were wide, “which may indicate lack of power and therefore not be conclusive,” Ms. Gooden said.

People living with HIV also had a 37% increased risk for hypertension, were 96% more likely to be prescribed lipid-lowering drugs, 2.4-times more likely to have chronic kidney disease, and 2.68-times more likely to experience all-cause mortality. The study couldn’t account for the type of HIV medications people living with the virus used, their viral load, or their CD4 counts – all of which have been found in previous studies to contribute to heart disease in people with HIV.

“That was the biggest limitation of our study,” Ms. Gooden said in an interview. “The fact that the risk of cardiovascular disease remains the same in the [first decade] and the later decade goes to show that even if antiretroviral therapies contributed to that … now or 20 years ago, it’s still not the entire reason for the risk.”

Steven Grinspoon, MD, of Harvard Medical School, Boston, is the lead author on the REPRIEVE trial, now testing statins as a treatment for people like those in this study. He told this news organization that this large analysis had one of the youngest cohorts of people living with HIV he’d seen to explore these issues. Additionally, it backs up what the team recently reported in the Journal of the American Medical Association – that plaque was present in 49% of 755 people living with HIV, despite having risk scores for cardiovascular disease in the normal range. This was as true for people younger than 40 as those older than 40.

For primary care clinicians, the message is that even relatively young people with HIV should be counseled early and often about amending traditional risk factors, while we wait for the results of REPRIEVE to say whether statins improve outcomes for people living with HIV, Dr. Grinspoon said in an interview.

“Sometimes physicians and primary care providers say, ‘Well I’ll focus my hypertension efforts on older people, who are closer to having heart attacks,’” Dr. Grinspoon said. “But this data suggests we should pay attention even in young people … and pay particular attention to women who wouldn’t have traditional risk scores that were very high at all, largely because they are women.”

The study was funded by Merck. Ms. Gooden has disclosed no relevant financial relationships. Dr. Grinspoon reports receiving personal and consulting fees from Theratechnologies and ViiV Healthcare.

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

People age 40 and younger living with HIV have a higher risk for heart disease than even their over-40 peers living with HIV – and that risk was 54% higher than the general public.

And this was among people without traditional heart disease risks, such as smoking and obesity.

“What’s surprising is that not only do we see that, yes, they do have increased risk, but this is after controlling for all of that – which means the mechanism underlying this risk,” said Tiffany Gooden, MPH and a PhD candidate at the University of Birmingham, England, who presented the data at the 11th International AIDS Society Conference on HIV Science (IAS 2021).

“If we’re using a non–HIV-validated assessment tool, you should always know that there could be a risk that you are under-recognizing,” she added.

Right now, there’s not a lot to aid clinicians in ferreting out this increased risk. Traditional cardiovascular risk assessment tools, like Framingham risk scores and atherosclerotic cardiovascular disease risk score from the American College of Cardiology, have been found to overlook the real risk of cardiovascular disease in people living with HIV. Plus, most guidelines, including those from the British HIV Medical Association and the American College of Cardiology, primarily focus screening on people 40 or older.

Ms. Gooden’s study drew data from The Health Improvement Network (THIN) database, which combines data from 800 primary care practices in the United Kingdom. Looking at data between January 2000 and January 2020, the investigators compared each person living with HIV with four peers not living with HIV, matched for age, gender, and practice. In total, 9,233 people living with HIV and 35,721 people without HIV were included in the analysis. Median age of participants was 41 years in people living with HIV and 40.4 years in people without HIV. About 35% of participants in both arms were women, and a greater proportion of participants living with HIV were Black, accounting for 22.5% of people living with HIV, versus 3.8% of the general population. Fewer people living with HIV were overweight or obese compared to people without HIV.

Researchers then tracked participants over time to identify the incidence of heart attack, stroke, peripheral vascular disease, and heart failure, as well as common risk factors for heart problems, such as high blood pressure, type 2 diabetes, chronic kidney disease, atrial fibrillation, and use of a lipid-lowering drug such as a statin.

The investigators then sectioned the data on heart disease risk by decade – 2000-2009 and 2010-2019 – in order to separate the potential impact of antiretroviral treatment (ART) drugs, from early combinations that have been associated with cardiovascular disease, to current drugs that are less likely to have that effect.

Overall risk for any kind of cardiovascular disease was 54% higher among people living with HIV of any age, compared to their age- and risk-matched peers. And when they broke the data down by age, they found that people younger than 40 had nearly twice the risk for any heart disease as their HIV-negative peers, which was a numerically higher risk than for people older than 40 – though not significantly so.

People living with HIV also had a 49% increased risk for stroke and a 59% increased risk for ischemic heart disease but no increased risk for peripheral vascular disease, heart failure, or heart attack. But the confidence intervals here were wide, “which may indicate lack of power and therefore not be conclusive,” Ms. Gooden said.

People living with HIV also had a 37% increased risk for hypertension, were 96% more likely to be prescribed lipid-lowering drugs, 2.4-times more likely to have chronic kidney disease, and 2.68-times more likely to experience all-cause mortality. The study couldn’t account for the type of HIV medications people living with the virus used, their viral load, or their CD4 counts – all of which have been found in previous studies to contribute to heart disease in people with HIV.

“That was the biggest limitation of our study,” Ms. Gooden said in an interview. “The fact that the risk of cardiovascular disease remains the same in the [first decade] and the later decade goes to show that even if antiretroviral therapies contributed to that … now or 20 years ago, it’s still not the entire reason for the risk.”

Steven Grinspoon, MD, of Harvard Medical School, Boston, is the lead author on the REPRIEVE trial, now testing statins as a treatment for people like those in this study. He told this news organization that this large analysis had one of the youngest cohorts of people living with HIV he’d seen to explore these issues. Additionally, it backs up what the team recently reported in the Journal of the American Medical Association – that plaque was present in 49% of 755 people living with HIV, despite having risk scores for cardiovascular disease in the normal range. This was as true for people younger than 40 as those older than 40.

For primary care clinicians, the message is that even relatively young people with HIV should be counseled early and often about amending traditional risk factors, while we wait for the results of REPRIEVE to say whether statins improve outcomes for people living with HIV, Dr. Grinspoon said in an interview.

“Sometimes physicians and primary care providers say, ‘Well I’ll focus my hypertension efforts on older people, who are closer to having heart attacks,’” Dr. Grinspoon said. “But this data suggests we should pay attention even in young people … and pay particular attention to women who wouldn’t have traditional risk scores that were very high at all, largely because they are women.”

The study was funded by Merck. Ms. Gooden has disclosed no relevant financial relationships. Dr. Grinspoon reports receiving personal and consulting fees from Theratechnologies and ViiV Healthcare.

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

People age 40 and younger living with HIV have a higher risk for heart disease than even their over-40 peers living with HIV – and that risk was 54% higher than the general public.

And this was among people without traditional heart disease risks, such as smoking and obesity.

“What’s surprising is that not only do we see that, yes, they do have increased risk, but this is after controlling for all of that – which means the mechanism underlying this risk,” said Tiffany Gooden, MPH and a PhD candidate at the University of Birmingham, England, who presented the data at the 11th International AIDS Society Conference on HIV Science (IAS 2021).

“If we’re using a non–HIV-validated assessment tool, you should always know that there could be a risk that you are under-recognizing,” she added.

Right now, there’s not a lot to aid clinicians in ferreting out this increased risk. Traditional cardiovascular risk assessment tools, like Framingham risk scores and atherosclerotic cardiovascular disease risk score from the American College of Cardiology, have been found to overlook the real risk of cardiovascular disease in people living with HIV. Plus, most guidelines, including those from the British HIV Medical Association and the American College of Cardiology, primarily focus screening on people 40 or older.

Ms. Gooden’s study drew data from The Health Improvement Network (THIN) database, which combines data from 800 primary care practices in the United Kingdom. Looking at data between January 2000 and January 2020, the investigators compared each person living with HIV with four peers not living with HIV, matched for age, gender, and practice. In total, 9,233 people living with HIV and 35,721 people without HIV were included in the analysis. Median age of participants was 41 years in people living with HIV and 40.4 years in people without HIV. About 35% of participants in both arms were women, and a greater proportion of participants living with HIV were Black, accounting for 22.5% of people living with HIV, versus 3.8% of the general population. Fewer people living with HIV were overweight or obese compared to people without HIV.

Researchers then tracked participants over time to identify the incidence of heart attack, stroke, peripheral vascular disease, and heart failure, as well as common risk factors for heart problems, such as high blood pressure, type 2 diabetes, chronic kidney disease, atrial fibrillation, and use of a lipid-lowering drug such as a statin.

The investigators then sectioned the data on heart disease risk by decade – 2000-2009 and 2010-2019 – in order to separate the potential impact of antiretroviral treatment (ART) drugs, from early combinations that have been associated with cardiovascular disease, to current drugs that are less likely to have that effect.

Overall risk for any kind of cardiovascular disease was 54% higher among people living with HIV of any age, compared to their age- and risk-matched peers. And when they broke the data down by age, they found that people younger than 40 had nearly twice the risk for any heart disease as their HIV-negative peers, which was a numerically higher risk than for people older than 40 – though not significantly so.

People living with HIV also had a 49% increased risk for stroke and a 59% increased risk for ischemic heart disease but no increased risk for peripheral vascular disease, heart failure, or heart attack. But the confidence intervals here were wide, “which may indicate lack of power and therefore not be conclusive,” Ms. Gooden said.

People living with HIV also had a 37% increased risk for hypertension, were 96% more likely to be prescribed lipid-lowering drugs, 2.4-times more likely to have chronic kidney disease, and 2.68-times more likely to experience all-cause mortality. The study couldn’t account for the type of HIV medications people living with the virus used, their viral load, or their CD4 counts – all of which have been found in previous studies to contribute to heart disease in people with HIV.

“That was the biggest limitation of our study,” Ms. Gooden said in an interview. “The fact that the risk of cardiovascular disease remains the same in the [first decade] and the later decade goes to show that even if antiretroviral therapies contributed to that … now or 20 years ago, it’s still not the entire reason for the risk.”

Steven Grinspoon, MD, of Harvard Medical School, Boston, is the lead author on the REPRIEVE trial, now testing statins as a treatment for people like those in this study. He told this news organization that this large analysis had one of the youngest cohorts of people living with HIV he’d seen to explore these issues. Additionally, it backs up what the team recently reported in the Journal of the American Medical Association – that plaque was present in 49% of 755 people living with HIV, despite having risk scores for cardiovascular disease in the normal range. This was as true for people younger than 40 as those older than 40.

For primary care clinicians, the message is that even relatively young people with HIV should be counseled early and often about amending traditional risk factors, while we wait for the results of REPRIEVE to say whether statins improve outcomes for people living with HIV, Dr. Grinspoon said in an interview.

“Sometimes physicians and primary care providers say, ‘Well I’ll focus my hypertension efforts on older people, who are closer to having heart attacks,’” Dr. Grinspoon said. “But this data suggests we should pay attention even in young people … and pay particular attention to women who wouldn’t have traditional risk scores that were very high at all, largely because they are women.”

The study was funded by Merck. Ms. Gooden has disclosed no relevant financial relationships. Dr. Grinspoon reports receiving personal and consulting fees from Theratechnologies and ViiV Healthcare.

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

Among patients hospitalized for COVID-19, those who had been taking statins had a substantially lower risk of death in a new large observational study.

Results showed that use of statins prior to admission was linked to a greater than 40% reduction in mortality and a greater than 25% reduction in risk of developing a severe outcome.

The findings come an analysis of data from the American Heart Association’s COVID-19 Cardiovascular Disease Registry on more than 10,000 patients hospitalized with COVID-19 at 104 hospitals across the United States published in PLoS One.

While several other studies have suggested benefits of statins in COVID-19, this is by far the largest study so far on this topic.

“I would say this is the most reliable study on statins in COVID-19 to date, with the results adjusted for many confounders, including socioeconomic factors and insurance type,” lead author Lori B. Daniels, MD, told this news organization. “However, it still an observational study and therefore falls short of a randomized study. But I would think a randomized study of statins in COVID-19 is probably not feasible, so this study provides excellent data at an observational level.”

After propensity matching for cardiovascular disease, results showed that most of the benefit of statins occurred in patients with known cardiovascular disease.

“While most patients taking statins will have cardiovascular disease, there are also many patients who take these drugs who don’t have heart disease but do have cardiovascular risk factors, such as those with raised cholesterol, or a family history of cardiovascular disease. For [such patients], the effect of statins was also in the same direction but it was not significant. This doesn’t exclude an effect,” noted Dr. Daniels, who is professor of medicine and director of cardiovascular intensive care at the University of California, San Diego.

“We are not saying that everyone should rush out and take a statin if they do not have risk factors for cardiovascular in order to lower their risk of dying from COVID. But if individuals do have an indication for a statin and are not taking one of these dugs this is another good reason to start taking them now,” she added.

The investigators embarked on the study because, although previous observational studies have found that statins may reduce the severity of COVID-19 infection, these studies have been limited in size with mostly single-center or regional studies, and some results have been conflicting. They therefore conducted the current, much larger analysis, in the AHA COVID-19 CVD Registry which systematically collected hospitalized patient–level data in a broad and diverse hospital and patient population across the United States.

For the analysis, the researchers analyzed data from 10,541 patients hospitalized with COVID-19 through September 2020 at 104 U.S. hospitals enrolled in the AHA registry to evaluate the associations between statin use and outcomes.

Most patients (71%) had either cardiovascular disease, hypertension, or both. Prior to admission, 42% of subjects used statins, with 7% being on statins alone and 35% on statins plus antihypertensives. Death (or discharge to hospice) occurred in 2,212 subjects (21%).

Results showed that outpatient use of statins, either alone or with antihypertensives, was associated with a 41% reduced risk of death (odds ratio, 0.59; 95% confidence interval, 0.50-0.69), after adjusting for demographic characteristics, underlying conditions, insurance status, hospital site, and concurrent medications. Statin use was also associated with a roughly 25% lower adjusted odds of developing severe disease.

Noting that patients on statins are also likely to be on antihypertensive medication, the researchers found that the statin benefit on mortality was seen in both patients taking a statin alone (OR, 0.54) and in those taking statins with an antihypertensive medication (OR, 0.60).

Use of antihypertensive drugs was associated with a smaller, albeit still substantial, 27% lower odds of death (OR, 0.73; 95% CI, 0.62-0.87).

In propensity-matched analyses, use of statins and/or antihypertensives was tied to a 32% reduced risk of death among those with a history of CVD and/or hypertension (OR, 0.68; 95% CI, 0.58-0.81). An observed 16% reduction in odds of death with statins and/or antihypertensive drugs among those without cardiovascular disease and/or hypertension was not statistically significant (OR, 0.84; 95% CI, 0.58-1.22).
 

Stabilizing the underlying disease

The researchers pointed out that the results of the propensity matching analysis are consistent with the hypothesis that the major benefit of these medications accrues from treating and/or stabilizing underlying disease.

“Although it is well known that statins improve long-term outcomes among patients with or at elevated risk for cardiovascular disease, the association with a large short-term benefit which accrues in the setting of hospitalization for COVID-19 is a new and intriguing finding,” they said.

They cited several “plausible mechanisms whereby statins could directly mitigate outcomes in COVID-19 beyond treating underlying disease conditions,” including anti-inflammatory effects and a direct inhibitory effect on the SARS-CoV-2 virus.

Dr. Daniels elaborated more on the potential mechanism at play in an interview: “I think what is happening is that the statin is stabilizing the coronary disease so patients are less likely to die from MI or stroke, and this gives them more time and strength to recover from COVID-19.”

She added: “Statins may also have some direct anti-COVID effects such as an anti-inflammatory actions, but I would guess that this is probably not the primary effect behind what we’re seeing here.”
 

‘Important clinical implications’

The authors say their findings have “important clinical implications.”

They noted that early in the pandemic there was speculation that certain medications, including statins, and the ACE inhibitor/angiotensin receptor blocker (ARB) classes of antihypertensives may confer an increased susceptibility to COVID-19 positivity and/or severity.

“Our study reinforces the AHA and others’ recommendations that not only is it safe to remain on these medications, but they may substantially reduce risk of severe COVID-19 and especially death from COVID-19, particularly statins, and particularly among those with associated underlying conditions,” the authors stressed.

Dr. Daniels added that, although statins are very safe drugs, there are always some patients who prefer not to take medication even if indicated, and others who may have borderline indications and decide not to take a statin at present.

“This study may persuade these patients that taking a statin is the right thing to do. It may give those patients on the cusp of thinking about taking one of these drugs a reason to go ahead,” she said.
 

‘Provocative but not definitive’

Commenting on the study, Robert Harrington, MD, professor of medicine and chair of the department of medicine at Stanford (Calif.) University, said: “These are interesting observational data but as such have all the limitations of nonrandomized comparisons despite the best attempts to adjust for a variety of potential confounders. For example, is this an effect of statins (perhaps through some anti-inflammatory mechanism) or is it more an effect that can be attributed to the patients who are prescribed and taking a statin, compared with those who are not?”

He added: “The primary clinical benefit of statins, based on many large randomized clinical trials, seems to be derived from their LDL lowering effect. Observational studies have suggested potential benefits from anti-inflammatory effects of statins, but the randomized trials have not confirmed these observations. So, the current data are interesting, even provocative, but ultimately hypothesis generating rather than definitive.”

Also commenting on the study, Steven Nissen, MD, professor of medicine at the Cleveland Clinic, said: “While statins have many established benefits, their role in preventing COVID-19 complications is very speculative. Like all observational studies, the current study must be viewed as hypothesis generating, not definitive evidence of benefit. There are many potential confounders. I’m skeptical.”

The authors of this study received no specific funding for this work and report no competing interests. Dr. Harrington was AHA president when the COVID registry was created and he is still a member of the AHA board, which has oversight over the project.

Among patients hospitalized for COVID-19, those who had been taking statins had a substantially lower risk of death in a new large observational study.

Results showed that use of statins prior to admission was linked to a greater than 40% reduction in mortality and a greater than 25% reduction in risk of developing a severe outcome.

The findings come an analysis of data from the American Heart Association’s COVID-19 Cardiovascular Disease Registry on more than 10,000 patients hospitalized with COVID-19 at 104 hospitals across the United States published in PLoS One.

While several other studies have suggested benefits of statins in COVID-19, this is by far the largest study so far on this topic.

“I would say this is the most reliable study on statins in COVID-19 to date, with the results adjusted for many confounders, including socioeconomic factors and insurance type,” lead author Lori B. Daniels, MD, told this news organization. “However, it still an observational study and therefore falls short of a randomized study. But I would think a randomized study of statins in COVID-19 is probably not feasible, so this study provides excellent data at an observational level.”

After propensity matching for cardiovascular disease, results showed that most of the benefit of statins occurred in patients with known cardiovascular disease.

“While most patients taking statins will have cardiovascular disease, there are also many patients who take these drugs who don’t have heart disease but do have cardiovascular risk factors, such as those with raised cholesterol, or a family history of cardiovascular disease. For [such patients], the effect of statins was also in the same direction but it was not significant. This doesn’t exclude an effect,” noted Dr. Daniels, who is professor of medicine and director of cardiovascular intensive care at the University of California, San Diego.

“We are not saying that everyone should rush out and take a statin if they do not have risk factors for cardiovascular in order to lower their risk of dying from COVID. But if individuals do have an indication for a statin and are not taking one of these dugs this is another good reason to start taking them now,” she added.

The investigators embarked on the study because, although previous observational studies have found that statins may reduce the severity of COVID-19 infection, these studies have been limited in size with mostly single-center or regional studies, and some results have been conflicting. They therefore conducted the current, much larger analysis, in the AHA COVID-19 CVD Registry which systematically collected hospitalized patient–level data in a broad and diverse hospital and patient population across the United States.

For the analysis, the researchers analyzed data from 10,541 patients hospitalized with COVID-19 through September 2020 at 104 U.S. hospitals enrolled in the AHA registry to evaluate the associations between statin use and outcomes.

Most patients (71%) had either cardiovascular disease, hypertension, or both. Prior to admission, 42% of subjects used statins, with 7% being on statins alone and 35% on statins plus antihypertensives. Death (or discharge to hospice) occurred in 2,212 subjects (21%).

Results showed that outpatient use of statins, either alone or with antihypertensives, was associated with a 41% reduced risk of death (odds ratio, 0.59; 95% confidence interval, 0.50-0.69), after adjusting for demographic characteristics, underlying conditions, insurance status, hospital site, and concurrent medications. Statin use was also associated with a roughly 25% lower adjusted odds of developing severe disease.

Noting that patients on statins are also likely to be on antihypertensive medication, the researchers found that the statin benefit on mortality was seen in both patients taking a statin alone (OR, 0.54) and in those taking statins with an antihypertensive medication (OR, 0.60).

Use of antihypertensive drugs was associated with a smaller, albeit still substantial, 27% lower odds of death (OR, 0.73; 95% CI, 0.62-0.87).

In propensity-matched analyses, use of statins and/or antihypertensives was tied to a 32% reduced risk of death among those with a history of CVD and/or hypertension (OR, 0.68; 95% CI, 0.58-0.81). An observed 16% reduction in odds of death with statins and/or antihypertensive drugs among those without cardiovascular disease and/or hypertension was not statistically significant (OR, 0.84; 95% CI, 0.58-1.22).
 

Stabilizing the underlying disease

The researchers pointed out that the results of the propensity matching analysis are consistent with the hypothesis that the major benefit of these medications accrues from treating and/or stabilizing underlying disease.

“Although it is well known that statins improve long-term outcomes among patients with or at elevated risk for cardiovascular disease, the association with a large short-term benefit which accrues in the setting of hospitalization for COVID-19 is a new and intriguing finding,” they said.

They cited several “plausible mechanisms whereby statins could directly mitigate outcomes in COVID-19 beyond treating underlying disease conditions,” including anti-inflammatory effects and a direct inhibitory effect on the SARS-CoV-2 virus.

Dr. Daniels elaborated more on the potential mechanism at play in an interview: “I think what is happening is that the statin is stabilizing the coronary disease so patients are less likely to die from MI or stroke, and this gives them more time and strength to recover from COVID-19.”

She added: “Statins may also have some direct anti-COVID effects such as an anti-inflammatory actions, but I would guess that this is probably not the primary effect behind what we’re seeing here.”
 

‘Important clinical implications’

The authors say their findings have “important clinical implications.”

They noted that early in the pandemic there was speculation that certain medications, including statins, and the ACE inhibitor/angiotensin receptor blocker (ARB) classes of antihypertensives may confer an increased susceptibility to COVID-19 positivity and/or severity.

“Our study reinforces the AHA and others’ recommendations that not only is it safe to remain on these medications, but they may substantially reduce risk of severe COVID-19 and especially death from COVID-19, particularly statins, and particularly among those with associated underlying conditions,” the authors stressed.

Dr. Daniels added that, although statins are very safe drugs, there are always some patients who prefer not to take medication even if indicated, and others who may have borderline indications and decide not to take a statin at present.

“This study may persuade these patients that taking a statin is the right thing to do. It may give those patients on the cusp of thinking about taking one of these drugs a reason to go ahead,” she said.
 

‘Provocative but not definitive’

Commenting on the study, Robert Harrington, MD, professor of medicine and chair of the department of medicine at Stanford (Calif.) University, said: “These are interesting observational data but as such have all the limitations of nonrandomized comparisons despite the best attempts to adjust for a variety of potential confounders. For example, is this an effect of statins (perhaps through some anti-inflammatory mechanism) or is it more an effect that can be attributed to the patients who are prescribed and taking a statin, compared with those who are not?”

He added: “The primary clinical benefit of statins, based on many large randomized clinical trials, seems to be derived from their LDL lowering effect. Observational studies have suggested potential benefits from anti-inflammatory effects of statins, but the randomized trials have not confirmed these observations. So, the current data are interesting, even provocative, but ultimately hypothesis generating rather than definitive.”

Also commenting on the study, Steven Nissen, MD, professor of medicine at the Cleveland Clinic, said: “While statins have many established benefits, their role in preventing COVID-19 complications is very speculative. Like all observational studies, the current study must be viewed as hypothesis generating, not definitive evidence of benefit. There are many potential confounders. I’m skeptical.”

The authors of this study received no specific funding for this work and report no competing interests. Dr. Harrington was AHA president when the COVID registry was created and he is still a member of the AHA board, which has oversight over the project.

Among patients hospitalized for COVID-19, those who had been taking statins had a substantially lower risk of death in a new large observational study.

Results showed that use of statins prior to admission was linked to a greater than 40% reduction in mortality and a greater than 25% reduction in risk of developing a severe outcome.

The findings come an analysis of data from the American Heart Association’s COVID-19 Cardiovascular Disease Registry on more than 10,000 patients hospitalized with COVID-19 at 104 hospitals across the United States published in PLoS One.

While several other studies have suggested benefits of statins in COVID-19, this is by far the largest study so far on this topic.

“I would say this is the most reliable study on statins in COVID-19 to date, with the results adjusted for many confounders, including socioeconomic factors and insurance type,” lead author Lori B. Daniels, MD, told this news organization. “However, it still an observational study and therefore falls short of a randomized study. But I would think a randomized study of statins in COVID-19 is probably not feasible, so this study provides excellent data at an observational level.”

After propensity matching for cardiovascular disease, results showed that most of the benefit of statins occurred in patients with known cardiovascular disease.

“While most patients taking statins will have cardiovascular disease, there are also many patients who take these drugs who don’t have heart disease but do have cardiovascular risk factors, such as those with raised cholesterol, or a family history of cardiovascular disease. For [such patients], the effect of statins was also in the same direction but it was not significant. This doesn’t exclude an effect,” noted Dr. Daniels, who is professor of medicine and director of cardiovascular intensive care at the University of California, San Diego.

“We are not saying that everyone should rush out and take a statin if they do not have risk factors for cardiovascular in order to lower their risk of dying from COVID. But if individuals do have an indication for a statin and are not taking one of these dugs this is another good reason to start taking them now,” she added.

The investigators embarked on the study because, although previous observational studies have found that statins may reduce the severity of COVID-19 infection, these studies have been limited in size with mostly single-center or regional studies, and some results have been conflicting. They therefore conducted the current, much larger analysis, in the AHA COVID-19 CVD Registry which systematically collected hospitalized patient–level data in a broad and diverse hospital and patient population across the United States.

For the analysis, the researchers analyzed data from 10,541 patients hospitalized with COVID-19 through September 2020 at 104 U.S. hospitals enrolled in the AHA registry to evaluate the associations between statin use and outcomes.

Most patients (71%) had either cardiovascular disease, hypertension, or both. Prior to admission, 42% of subjects used statins, with 7% being on statins alone and 35% on statins plus antihypertensives. Death (or discharge to hospice) occurred in 2,212 subjects (21%).

Results showed that outpatient use of statins, either alone or with antihypertensives, was associated with a 41% reduced risk of death (odds ratio, 0.59; 95% confidence interval, 0.50-0.69), after adjusting for demographic characteristics, underlying conditions, insurance status, hospital site, and concurrent medications. Statin use was also associated with a roughly 25% lower adjusted odds of developing severe disease.

Noting that patients on statins are also likely to be on antihypertensive medication, the researchers found that the statin benefit on mortality was seen in both patients taking a statin alone (OR, 0.54) and in those taking statins with an antihypertensive medication (OR, 0.60).

Use of antihypertensive drugs was associated with a smaller, albeit still substantial, 27% lower odds of death (OR, 0.73; 95% CI, 0.62-0.87).

In propensity-matched analyses, use of statins and/or antihypertensives was tied to a 32% reduced risk of death among those with a history of CVD and/or hypertension (OR, 0.68; 95% CI, 0.58-0.81). An observed 16% reduction in odds of death with statins and/or antihypertensive drugs among those without cardiovascular disease and/or hypertension was not statistically significant (OR, 0.84; 95% CI, 0.58-1.22).
 

Stabilizing the underlying disease

The researchers pointed out that the results of the propensity matching analysis are consistent with the hypothesis that the major benefit of these medications accrues from treating and/or stabilizing underlying disease.

“Although it is well known that statins improve long-term outcomes among patients with or at elevated risk for cardiovascular disease, the association with a large short-term benefit which accrues in the setting of hospitalization for COVID-19 is a new and intriguing finding,” they said.

They cited several “plausible mechanisms whereby statins could directly mitigate outcomes in COVID-19 beyond treating underlying disease conditions,” including anti-inflammatory effects and a direct inhibitory effect on the SARS-CoV-2 virus.

Dr. Daniels elaborated more on the potential mechanism at play in an interview: “I think what is happening is that the statin is stabilizing the coronary disease so patients are less likely to die from MI or stroke, and this gives them more time and strength to recover from COVID-19.”

She added: “Statins may also have some direct anti-COVID effects such as an anti-inflammatory actions, but I would guess that this is probably not the primary effect behind what we’re seeing here.”
 

‘Important clinical implications’

The authors say their findings have “important clinical implications.”

They noted that early in the pandemic there was speculation that certain medications, including statins, and the ACE inhibitor/angiotensin receptor blocker (ARB) classes of antihypertensives may confer an increased susceptibility to COVID-19 positivity and/or severity.

“Our study reinforces the AHA and others’ recommendations that not only is it safe to remain on these medications, but they may substantially reduce risk of severe COVID-19 and especially death from COVID-19, particularly statins, and particularly among those with associated underlying conditions,” the authors stressed.

Dr. Daniels added that, although statins are very safe drugs, there are always some patients who prefer not to take medication even if indicated, and others who may have borderline indications and decide not to take a statin at present.

“This study may persuade these patients that taking a statin is the right thing to do. It may give those patients on the cusp of thinking about taking one of these drugs a reason to go ahead,” she said.
 

‘Provocative but not definitive’

Commenting on the study, Robert Harrington, MD, professor of medicine and chair of the department of medicine at Stanford (Calif.) University, said: “These are interesting observational data but as such have all the limitations of nonrandomized comparisons despite the best attempts to adjust for a variety of potential confounders. For example, is this an effect of statins (perhaps through some anti-inflammatory mechanism) or is it more an effect that can be attributed to the patients who are prescribed and taking a statin, compared with those who are not?”

He added: “The primary clinical benefit of statins, based on many large randomized clinical trials, seems to be derived from their LDL lowering effect. Observational studies have suggested potential benefits from anti-inflammatory effects of statins, but the randomized trials have not confirmed these observations. So, the current data are interesting, even provocative, but ultimately hypothesis generating rather than definitive.”

Also commenting on the study, Steven Nissen, MD, professor of medicine at the Cleveland Clinic, said: “While statins have many established benefits, their role in preventing COVID-19 complications is very speculative. Like all observational studies, the current study must be viewed as hypothesis generating, not definitive evidence of benefit. There are many potential confounders. I’m skeptical.”

The authors of this study received no specific funding for this work and report no competing interests. Dr. Harrington was AHA president when the COVID registry was created and he is still a member of the AHA board, which has oversight over the project.

Five risk factors might help pinpoint patients at risk of developing device-related thrombus (DRT), itself an important risk factor for cerebrovascular events, in patients with implants for left atrial appendage occlusion (LAAO), new research suggests.

The identified independent predictors of DRT in the largest dedicated multicenter LAAO-DRT registry to date were presence of a hypercoagulability disorder, pericardial effusion, renal insufficiency, an implantation depth greater than 10 mm from the pulmonary ridge, and presence of nonparoxysmal atrial fibrillation (AFib).

“Unfortunately, most of them are not modifiable, like hypercoaguable disorders or nonparoxysmal atrial fibrillation. But we can avoid deep implants because that’s been associated with creating a little bit of a crater or valley where the clot can form,” senior author Mohamad Alkhouli, MD, said in an interview.

But most important, and “really why we wanted to do this,” he said, is that “we want to give the patient a realistic prediction of adverse events for this procedure.”

LAAO has taken off in recent years for preventing thrombus formation and stroke in patients with AFib. Predicting DRT is a priority for the LAAO field, the authors note, especially given its expansion to younger, lower-risk patients and the increasing procedural volumes.

“This is a problem, DRT, that’s been discussed a lot because this is a preventative procedure,” observed Dr. Alkhouli, professor of medicine at Mayo Medical School, Rochester, Minn.

“The actual stroke risk every year – even if you don’t take any blood thinner and you have a CHADsVASc score of 9, the highest – is 11%. So if the chance of having thrombus is close, then that’s not a good tradeoff.”

Previous studies have also identified implantation depth and nonparoxysmal AFib as risk factors for DRT. But most of them have been small, he noted, with one of the largest reporting 65 DRTs in four prospective trials.

To cast a wider net, the investigators, led by Trevor Simard, MD, also from the Mayo Clinic, invited more than 50 international sites to contribute data to the registry. Of these, 37 centers reported on 237 DRTs and 474 device-matched control subjects from the same site.

Three-fourths of patients received a first-generation Watchman or a FLEX device (Boston Scientific).

Medical regimens were similar between the DRT and control cohorts at discharge after LAA closure. Most patients were managed with single (36.3%) or dual antiplatelet therapy (26.2%) at the time of DRT diagnosis.

As reported July 19 in the Journal of the American College of Cardiology, the timing of DRT development varied widely, with 24.9% appearing in the first 45 days, 38.8% between days 45 and 180, 16.0% between days 180 to 365, and 20.3% beyond 1 year. At last known follow-up, one-quarter of patients had DRT.

The odds ratios for DRT associated with the five identified risk factors were:

• 17.50 (95% confidence interval, 3.39-90.45) for hypercoagulability disorder
• 13.45 (95% CI, 1.46-123.52) for pericardial effusion
• 4.02 (95% CI, 1.22-13.25) for renal insufficiency
• 2.41 (95% CI, 1.57-3.69) for implantation depth >10 mm
• 1.90 (95% CI, 1.22-2.97) for nonparoxysmal AFib

The risk for a composite of death, ischemic stroke, and systemic embolization was twofold higher in the DRT cohort than in the control cohort (29.5% vs. 14.4%; hazard ratio, 2.37; 95% CI, 1.58-3.56) and driven by a higher rate of ischemic stroke (16.9% vs. 3.6%; HR, 3.49; 95% CI, 1.35-9.00).

The incidence of bleeding and intracerebral hemorrhage, however, was similar in the DRT and control cohorts.

One of the surprises of the study was that medications prescribed in the short term after LAA closure were not associated with DRT, Dr. Alkhouli said. A previous meta-analysis of 66 studies by the investigators also found that antithrombotic regimen did not explain the heterogeneity of DRT formation.

“I think we’ll have to take that with a grain of salt, because there’s so many variations in the practice, and this is observational data. But that, in my mind, brings up a mechanistic issue,” he said.

It’s often recommended “that we should put patients on blood thinners for 3 months or 6 weeks, or whatever it is, to decrease the chance of thrombus, assuming the patients will have a normal endothelialization of the device,” Dr. Alkhouli said.

“Well, we know that’s not the reality,” he continued. “We know many patients don’t endothelialize, and, even if some patients do, there may be some endothelial damage. So I think the whole mechanism of prescribing a little bit of a blood thinner to avoid that risk may be missing the point. It’s a bit more complex than that, evidenced also by the fact that three-fourths of all the DRTs happened after 45 days, when patients are typically not taking a blood thinner.”

Based on the five independent risk factors, the investigators created a clinical DRT risk score that assigned 1 point for renal insufficiency, implantation depth greater than 10 mm from the pulmonary ridge, and nonparoxysmal AFib; and 4 points for iatrogenic pericardial effusion and for hypercoagulability disorder. Low risk was categorized as 1 point and high risk as 2 or more points.

The presence of one major risk factor or two minor risk factors, for example, led to a 2.1-fold increased risk for DRT, compared with those with no DRT risk factors.

The risk score will require validation in a prospective cohort but is “a step forward in addressing DRT” and triaging patients, Dr. Alkhouli said. The findings highlight the need to avoid deep device implantation and the importance of shared decision-making with patients, especially with those at high risk.

“And third, which is most important, I think, in my mind, is that it tells us not to put a blind eye to this topic and just say with improved devices it will go away,” he said. “That’s a bit unrealistic.”

In an accompanying editorial, Oussama Wazni, MD, Walid Saliba, MD, and Ayman A. Hussein, MD, all from the Cleveland Clinic, write that “the study sheds light on this yet unresolved issue, and the observations may help with risk stratification and optimization of procedural techniques.”

Whereas many of the nonmodifiable risk factors are helpful in shared decision-making decisions, they continue, “knowledge of these risk factors may not preclude implantation in patients who are otherwise at risk of both stroke off anticoagulation and bleeding on anticoagulation.”

Dr. Wazni and colleagues acknowledge that the small number of events in the study limits statistical power for definitive conclusions and say that further studies are needed to clarify the natural history of DRTs and their management, resolution, and impact on cardiovascular events.

Practitioners should also continue to cautiously assess for LAAO clinical indications for implant, according to the editorialists, who point out that the regulatory approval language in the United States was “flexible and nonspecific.”

“As the field grows wider, enhancing LAAO safety with optimal design, implantation, and periprocedural management is critically important, yet the main focus should remain on optimal patient selection for the purpose of achieving safe and successful outcomes,” the editorialists conclude.

Dr. Alkhouli has served as a consultant for Boston Scientific. Coauthor disclosures are listed in the paper. Dr. Wazni and Dr. Hussein have received research grant support from Boston Scientific. Dr. Wazni and Dr. Saliba have been consultants for Boston Scientific.

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

Five risk factors might help pinpoint patients at risk of developing device-related thrombus (DRT), itself an important risk factor for cerebrovascular events, in patients with implants for left atrial appendage occlusion (LAAO), new research suggests.

The identified independent predictors of DRT in the largest dedicated multicenter LAAO-DRT registry to date were presence of a hypercoagulability disorder, pericardial effusion, renal insufficiency, an implantation depth greater than 10 mm from the pulmonary ridge, and presence of nonparoxysmal atrial fibrillation (AFib).

“Unfortunately, most of them are not modifiable, like hypercoaguable disorders or nonparoxysmal atrial fibrillation. But we can avoid deep implants because that’s been associated with creating a little bit of a crater or valley where the clot can form,” senior author Mohamad Alkhouli, MD, said in an interview.

But most important, and “really why we wanted to do this,” he said, is that “we want to give the patient a realistic prediction of adverse events for this procedure.”

LAAO has taken off in recent years for preventing thrombus formation and stroke in patients with AFib. Predicting DRT is a priority for the LAAO field, the authors note, especially given its expansion to younger, lower-risk patients and the increasing procedural volumes.

“This is a problem, DRT, that’s been discussed a lot because this is a preventative procedure,” observed Dr. Alkhouli, professor of medicine at Mayo Medical School, Rochester, Minn.

“The actual stroke risk every year – even if you don’t take any blood thinner and you have a CHADsVASc score of 9, the highest – is 11%. So if the chance of having thrombus is close, then that’s not a good tradeoff.”

Previous studies have also identified implantation depth and nonparoxysmal AFib as risk factors for DRT. But most of them have been small, he noted, with one of the largest reporting 65 DRTs in four prospective trials.

To cast a wider net, the investigators, led by Trevor Simard, MD, also from the Mayo Clinic, invited more than 50 international sites to contribute data to the registry. Of these, 37 centers reported on 237 DRTs and 474 device-matched control subjects from the same site.

Three-fourths of patients received a first-generation Watchman or a FLEX device (Boston Scientific).

Medical regimens were similar between the DRT and control cohorts at discharge after LAA closure. Most patients were managed with single (36.3%) or dual antiplatelet therapy (26.2%) at the time of DRT diagnosis.

As reported July 19 in the Journal of the American College of Cardiology, the timing of DRT development varied widely, with 24.9% appearing in the first 45 days, 38.8% between days 45 and 180, 16.0% between days 180 to 365, and 20.3% beyond 1 year. At last known follow-up, one-quarter of patients had DRT.

The odds ratios for DRT associated with the five identified risk factors were:

• 17.50 (95% confidence interval, 3.39-90.45) for hypercoagulability disorder
• 13.45 (95% CI, 1.46-123.52) for pericardial effusion
• 4.02 (95% CI, 1.22-13.25) for renal insufficiency
• 2.41 (95% CI, 1.57-3.69) for implantation depth >10 mm
• 1.90 (95% CI, 1.22-2.97) for nonparoxysmal AFib

The risk for a composite of death, ischemic stroke, and systemic embolization was twofold higher in the DRT cohort than in the control cohort (29.5% vs. 14.4%; hazard ratio, 2.37; 95% CI, 1.58-3.56) and driven by a higher rate of ischemic stroke (16.9% vs. 3.6%; HR, 3.49; 95% CI, 1.35-9.00).

The incidence of bleeding and intracerebral hemorrhage, however, was similar in the DRT and control cohorts.

One of the surprises of the study was that medications prescribed in the short term after LAA closure were not associated with DRT, Dr. Alkhouli said. A previous meta-analysis of 66 studies by the investigators also found that antithrombotic regimen did not explain the heterogeneity of DRT formation.

“I think we’ll have to take that with a grain of salt, because there’s so many variations in the practice, and this is observational data. But that, in my mind, brings up a mechanistic issue,” he said.

It’s often recommended “that we should put patients on blood thinners for 3 months or 6 weeks, or whatever it is, to decrease the chance of thrombus, assuming the patients will have a normal endothelialization of the device,” Dr. Alkhouli said.

“Well, we know that’s not the reality,” he continued. “We know many patients don’t endothelialize, and, even if some patients do, there may be some endothelial damage. So I think the whole mechanism of prescribing a little bit of a blood thinner to avoid that risk may be missing the point. It’s a bit more complex than that, evidenced also by the fact that three-fourths of all the DRTs happened after 45 days, when patients are typically not taking a blood thinner.”

Based on the five independent risk factors, the investigators created a clinical DRT risk score that assigned 1 point for renal insufficiency, implantation depth greater than 10 mm from the pulmonary ridge, and nonparoxysmal AFib; and 4 points for iatrogenic pericardial effusion and for hypercoagulability disorder. Low risk was categorized as 1 point and high risk as 2 or more points.

The presence of one major risk factor or two minor risk factors, for example, led to a 2.1-fold increased risk for DRT, compared with those with no DRT risk factors.

The risk score will require validation in a prospective cohort but is “a step forward in addressing DRT” and triaging patients, Dr. Alkhouli said. The findings highlight the need to avoid deep device implantation and the importance of shared decision-making with patients, especially with those at high risk.

“And third, which is most important, I think, in my mind, is that it tells us not to put a blind eye to this topic and just say with improved devices it will go away,” he said. “That’s a bit unrealistic.”

In an accompanying editorial, Oussama Wazni, MD, Walid Saliba, MD, and Ayman A. Hussein, MD, all from the Cleveland Clinic, write that “the study sheds light on this yet unresolved issue, and the observations may help with risk stratification and optimization of procedural techniques.”

Whereas many of the nonmodifiable risk factors are helpful in shared decision-making decisions, they continue, “knowledge of these risk factors may not preclude implantation in patients who are otherwise at risk of both stroke off anticoagulation and bleeding on anticoagulation.”

Dr. Wazni and colleagues acknowledge that the small number of events in the study limits statistical power for definitive conclusions and say that further studies are needed to clarify the natural history of DRTs and their management, resolution, and impact on cardiovascular events.

Practitioners should also continue to cautiously assess for LAAO clinical indications for implant, according to the editorialists, who point out that the regulatory approval language in the United States was “flexible and nonspecific.”

“As the field grows wider, enhancing LAAO safety with optimal design, implantation, and periprocedural management is critically important, yet the main focus should remain on optimal patient selection for the purpose of achieving safe and successful outcomes,” the editorialists conclude.

Dr. Alkhouli has served as a consultant for Boston Scientific. Coauthor disclosures are listed in the paper. Dr. Wazni and Dr. Hussein have received research grant support from Boston Scientific. Dr. Wazni and Dr. Saliba have been consultants for Boston Scientific.

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

Five risk factors might help pinpoint patients at risk of developing device-related thrombus (DRT), itself an important risk factor for cerebrovascular events, in patients with implants for left atrial appendage occlusion (LAAO), new research suggests.

The identified independent predictors of DRT in the largest dedicated multicenter LAAO-DRT registry to date were presence of a hypercoagulability disorder, pericardial effusion, renal insufficiency, an implantation depth greater than 10 mm from the pulmonary ridge, and presence of nonparoxysmal atrial fibrillation (AFib).

“Unfortunately, most of them are not modifiable, like hypercoaguable disorders or nonparoxysmal atrial fibrillation. But we can avoid deep implants because that’s been associated with creating a little bit of a crater or valley where the clot can form,” senior author Mohamad Alkhouli, MD, said in an interview.

But most important, and “really why we wanted to do this,” he said, is that “we want to give the patient a realistic prediction of adverse events for this procedure.”

LAAO has taken off in recent years for preventing thrombus formation and stroke in patients with AFib. Predicting DRT is a priority for the LAAO field, the authors note, especially given its expansion to younger, lower-risk patients and the increasing procedural volumes.

“This is a problem, DRT, that’s been discussed a lot because this is a preventative procedure,” observed Dr. Alkhouli, professor of medicine at Mayo Medical School, Rochester, Minn.

“The actual stroke risk every year – even if you don’t take any blood thinner and you have a CHADsVASc score of 9, the highest – is 11%. So if the chance of having thrombus is close, then that’s not a good tradeoff.”

Previous studies have also identified implantation depth and nonparoxysmal AFib as risk factors for DRT. But most of them have been small, he noted, with one of the largest reporting 65 DRTs in four prospective trials.

To cast a wider net, the investigators, led by Trevor Simard, MD, also from the Mayo Clinic, invited more than 50 international sites to contribute data to the registry. Of these, 37 centers reported on 237 DRTs and 474 device-matched control subjects from the same site.

Three-fourths of patients received a first-generation Watchman or a FLEX device (Boston Scientific).

Medical regimens were similar between the DRT and control cohorts at discharge after LAA closure. Most patients were managed with single (36.3%) or dual antiplatelet therapy (26.2%) at the time of DRT diagnosis.

As reported July 19 in the Journal of the American College of Cardiology, the timing of DRT development varied widely, with 24.9% appearing in the first 45 days, 38.8% between days 45 and 180, 16.0% between days 180 to 365, and 20.3% beyond 1 year. At last known follow-up, one-quarter of patients had DRT.

The odds ratios for DRT associated with the five identified risk factors were:

• 17.50 (95% confidence interval, 3.39-90.45) for hypercoagulability disorder
• 13.45 (95% CI, 1.46-123.52) for pericardial effusion
• 4.02 (95% CI, 1.22-13.25) for renal insufficiency
• 2.41 (95% CI, 1.57-3.69) for implantation depth >10 mm
• 1.90 (95% CI, 1.22-2.97) for nonparoxysmal AFib

The risk for a composite of death, ischemic stroke, and systemic embolization was twofold higher in the DRT cohort than in the control cohort (29.5% vs. 14.4%; hazard ratio, 2.37; 95% CI, 1.58-3.56) and driven by a higher rate of ischemic stroke (16.9% vs. 3.6%; HR, 3.49; 95% CI, 1.35-9.00).

The incidence of bleeding and intracerebral hemorrhage, however, was similar in the DRT and control cohorts.

One of the surprises of the study was that medications prescribed in the short term after LAA closure were not associated with DRT, Dr. Alkhouli said. A previous meta-analysis of 66 studies by the investigators also found that antithrombotic regimen did not explain the heterogeneity of DRT formation.

“I think we’ll have to take that with a grain of salt, because there’s so many variations in the practice, and this is observational data. But that, in my mind, brings up a mechanistic issue,” he said.

It’s often recommended “that we should put patients on blood thinners for 3 months or 6 weeks, or whatever it is, to decrease the chance of thrombus, assuming the patients will have a normal endothelialization of the device,” Dr. Alkhouli said.

“Well, we know that’s not the reality,” he continued. “We know many patients don’t endothelialize, and, even if some patients do, there may be some endothelial damage. So I think the whole mechanism of prescribing a little bit of a blood thinner to avoid that risk may be missing the point. It’s a bit more complex than that, evidenced also by the fact that three-fourths of all the DRTs happened after 45 days, when patients are typically not taking a blood thinner.”

Based on the five independent risk factors, the investigators created a clinical DRT risk score that assigned 1 point for renal insufficiency, implantation depth greater than 10 mm from the pulmonary ridge, and nonparoxysmal AFib; and 4 points for iatrogenic pericardial effusion and for hypercoagulability disorder. Low risk was categorized as 1 point and high risk as 2 or more points.

The presence of one major risk factor or two minor risk factors, for example, led to a 2.1-fold increased risk for DRT, compared with those with no DRT risk factors.

The risk score will require validation in a prospective cohort but is “a step forward in addressing DRT” and triaging patients, Dr. Alkhouli said. The findings highlight the need to avoid deep device implantation and the importance of shared decision-making with patients, especially with those at high risk.

“And third, which is most important, I think, in my mind, is that it tells us not to put a blind eye to this topic and just say with improved devices it will go away,” he said. “That’s a bit unrealistic.”

In an accompanying editorial, Oussama Wazni, MD, Walid Saliba, MD, and Ayman A. Hussein, MD, all from the Cleveland Clinic, write that “the study sheds light on this yet unresolved issue, and the observations may help with risk stratification and optimization of procedural techniques.”

Whereas many of the nonmodifiable risk factors are helpful in shared decision-making decisions, they continue, “knowledge of these risk factors may not preclude implantation in patients who are otherwise at risk of both stroke off anticoagulation and bleeding on anticoagulation.”

Dr. Wazni and colleagues acknowledge that the small number of events in the study limits statistical power for definitive conclusions and say that further studies are needed to clarify the natural history of DRTs and their management, resolution, and impact on cardiovascular events.

Practitioners should also continue to cautiously assess for LAAO clinical indications for implant, according to the editorialists, who point out that the regulatory approval language in the United States was “flexible and nonspecific.”

“As the field grows wider, enhancing LAAO safety with optimal design, implantation, and periprocedural management is critically important, yet the main focus should remain on optimal patient selection for the purpose of achieving safe and successful outcomes,” the editorialists conclude.

Dr. Alkhouli has served as a consultant for Boston Scientific. Coauthor disclosures are listed in the paper. Dr. Wazni and Dr. Hussein have received research grant support from Boston Scientific. Dr. Wazni and Dr. Saliba have been consultants for Boston Scientific.

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

Data from a long-term study suggest that testosterone replacement therapy (TRT) for men with hypogonadism may reduce the risk for major adverse cardiovascular events. Previous studies have yielded conflicting results on whether there is a benefit.

The latest results come from a study of 805 men with hypogonadism from Germany and Qatar who were followed for nearly a decade. For those who received parenteral testosterone 1,000 mg every 12 weeks, there were improvements in classical cardiovascular risk factors, such as obesity, lipid level, and inflammatory markers, whereas among those who chose not to take testosterone (control patients), all of these factors worsened.

In addition, there were only 16 deaths among patients in the TRT group, and none of the deaths were from myocardial infarction or stroke. In contrast, there were 74 deaths among the control patients, as well as 70 cases of MI and 59 strokes.

The men in the study were all at relatively high risk for cardiovascular adverse events. In the TRT group, the mean Framingham Risk score was 15.5; in the control group, it was 15.8. This translates into mean 10-year risks of 22.7% and 23.5%, respectively.

“Given that all these men would normally have been expected to suffer a heart attack or stroke in the next 5-10 years with no other intervention, it was a real surprise to see no cardiovascular events at all in the group on testosterone therapy. It’s clear that this treatment can significantly reduce the risks in this particular group,” commented lead investigator Omar Aboumarzouk, MD, from Hamad Medical in Doha, Qatar.

He presented the new data at the 2021 annual congress of the European Association of Urology.

Dr. Aboumarzouk emphasized, however, that, “while men need testosterone for certain psychological and biological functions, only those with low levels who display other symptoms are likely to benefit from testosterone therapy.”

Maarten Albersen, MD, a urologist at the University of Leuven (Belgium), who was not involved in the study, noted that, although the study showed a reduction in major adverse cardiovascular events and mortality among the men who received TRT, the risk scores were in the intermediate range, and the men in the TRT group were slightly younger and were at slightly lower risk at baseline.

“The study was long enough to see differences in the rate of cardiovascular events. However, the numbers involved and the fact that the trial was not randomized mean it’s still difficult to draw any hard conclusions,” he said.
 

Registry study

The data came from a cumulative registry study begun in 2004 to assess the long-term efficacy and safety of TRT every 3 months in men with hypogonadism. The study, conducted in Bremen, Dresden, and Muenster in Germany, as well as in Doha, Qatar, is ongoing.

At total of 805 men were enrolled; 412 received TRT, and 393 declined testosterone replacement and served as control patients.

The investigators reported 10-year data. Statistical models controlled for age, body mass index, smoking, alcohol, total and HDL cholesterol level, systolic blood pressure, and type 2 diabetes.

The median age at baseline was lower among those in the TRT arm, at 57.7 years versus 63.7 years for control patients (P < .001).

All classical cardiovascular risk factors, including obesity, glycemic control, lipid pattern, and C-reactive protein, improved in the TRT group and worsened in the control group.

Dr. Albersen noted that “a new trial is now underway, aiming to recruit 6,000 participants, and this should provide definitive answers on the cardiovascular risks or even benefits of hormone therapy in men with low testosterone.”

No funding source for the study was reported. Dr. Aboumarzouk and Dr. Albersen have disclosed no relevant financial relationships.

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

Data from a long-term study suggest that testosterone replacement therapy (TRT) for men with hypogonadism may reduce the risk for major adverse cardiovascular events. Previous studies have yielded conflicting results on whether there is a benefit.

The latest results come from a study of 805 men with hypogonadism from Germany and Qatar who were followed for nearly a decade. For those who received parenteral testosterone 1,000 mg every 12 weeks, there were improvements in classical cardiovascular risk factors, such as obesity, lipid level, and inflammatory markers, whereas among those who chose not to take testosterone (control patients), all of these factors worsened.

In addition, there were only 16 deaths among patients in the TRT group, and none of the deaths were from myocardial infarction or stroke. In contrast, there were 74 deaths among the control patients, as well as 70 cases of MI and 59 strokes.

The men in the study were all at relatively high risk for cardiovascular adverse events. In the TRT group, the mean Framingham Risk score was 15.5; in the control group, it was 15.8. This translates into mean 10-year risks of 22.7% and 23.5%, respectively.

“Given that all these men would normally have been expected to suffer a heart attack or stroke in the next 5-10 years with no other intervention, it was a real surprise to see no cardiovascular events at all in the group on testosterone therapy. It’s clear that this treatment can significantly reduce the risks in this particular group,” commented lead investigator Omar Aboumarzouk, MD, from Hamad Medical in Doha, Qatar.

He presented the new data at the 2021 annual congress of the European Association of Urology.

Dr. Aboumarzouk emphasized, however, that, “while men need testosterone for certain psychological and biological functions, only those with low levels who display other symptoms are likely to benefit from testosterone therapy.”

Maarten Albersen, MD, a urologist at the University of Leuven (Belgium), who was not involved in the study, noted that, although the study showed a reduction in major adverse cardiovascular events and mortality among the men who received TRT, the risk scores were in the intermediate range, and the men in the TRT group were slightly younger and were at slightly lower risk at baseline.

“The study was long enough to see differences in the rate of cardiovascular events. However, the numbers involved and the fact that the trial was not randomized mean it’s still difficult to draw any hard conclusions,” he said.
 

Registry study

The data came from a cumulative registry study begun in 2004 to assess the long-term efficacy and safety of TRT every 3 months in men with hypogonadism. The study, conducted in Bremen, Dresden, and Muenster in Germany, as well as in Doha, Qatar, is ongoing.

At total of 805 men were enrolled; 412 received TRT, and 393 declined testosterone replacement and served as control patients.

The investigators reported 10-year data. Statistical models controlled for age, body mass index, smoking, alcohol, total and HDL cholesterol level, systolic blood pressure, and type 2 diabetes.

The median age at baseline was lower among those in the TRT arm, at 57.7 years versus 63.7 years for control patients (P < .001).

All classical cardiovascular risk factors, including obesity, glycemic control, lipid pattern, and C-reactive protein, improved in the TRT group and worsened in the control group.

Dr. Albersen noted that “a new trial is now underway, aiming to recruit 6,000 participants, and this should provide definitive answers on the cardiovascular risks or even benefits of hormone therapy in men with low testosterone.”

No funding source for the study was reported. Dr. Aboumarzouk and Dr. Albersen have disclosed no relevant financial relationships.

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

Data from a long-term study suggest that testosterone replacement therapy (TRT) for men with hypogonadism may reduce the risk for major adverse cardiovascular events. Previous studies have yielded conflicting results on whether there is a benefit.

The latest results come from a study of 805 men with hypogonadism from Germany and Qatar who were followed for nearly a decade. For those who received parenteral testosterone 1,000 mg every 12 weeks, there were improvements in classical cardiovascular risk factors, such as obesity, lipid level, and inflammatory markers, whereas among those who chose not to take testosterone (control patients), all of these factors worsened.

In addition, there were only 16 deaths among patients in the TRT group, and none of the deaths were from myocardial infarction or stroke. In contrast, there were 74 deaths among the control patients, as well as 70 cases of MI and 59 strokes.

The men in the study were all at relatively high risk for cardiovascular adverse events. In the TRT group, the mean Framingham Risk score was 15.5; in the control group, it was 15.8. This translates into mean 10-year risks of 22.7% and 23.5%, respectively.

“Given that all these men would normally have been expected to suffer a heart attack or stroke in the next 5-10 years with no other intervention, it was a real surprise to see no cardiovascular events at all in the group on testosterone therapy. It’s clear that this treatment can significantly reduce the risks in this particular group,” commented lead investigator Omar Aboumarzouk, MD, from Hamad Medical in Doha, Qatar.

He presented the new data at the 2021 annual congress of the European Association of Urology.

Dr. Aboumarzouk emphasized, however, that, “while men need testosterone for certain psychological and biological functions, only those with low levels who display other symptoms are likely to benefit from testosterone therapy.”

Maarten Albersen, MD, a urologist at the University of Leuven (Belgium), who was not involved in the study, noted that, although the study showed a reduction in major adverse cardiovascular events and mortality among the men who received TRT, the risk scores were in the intermediate range, and the men in the TRT group were slightly younger and were at slightly lower risk at baseline.

“The study was long enough to see differences in the rate of cardiovascular events. However, the numbers involved and the fact that the trial was not randomized mean it’s still difficult to draw any hard conclusions,” he said.
 

Registry study

The data came from a cumulative registry study begun in 2004 to assess the long-term efficacy and safety of TRT every 3 months in men with hypogonadism. The study, conducted in Bremen, Dresden, and Muenster in Germany, as well as in Doha, Qatar, is ongoing.

At total of 805 men were enrolled; 412 received TRT, and 393 declined testosterone replacement and served as control patients.

The investigators reported 10-year data. Statistical models controlled for age, body mass index, smoking, alcohol, total and HDL cholesterol level, systolic blood pressure, and type 2 diabetes.

The median age at baseline was lower among those in the TRT arm, at 57.7 years versus 63.7 years for control patients (P < .001).

All classical cardiovascular risk factors, including obesity, glycemic control, lipid pattern, and C-reactive protein, improved in the TRT group and worsened in the control group.

Dr. Albersen noted that “a new trial is now underway, aiming to recruit 6,000 participants, and this should provide definitive answers on the cardiovascular risks or even benefits of hormone therapy in men with low testosterone.”

No funding source for the study was reported. Dr. Aboumarzouk and Dr. Albersen have disclosed no relevant financial relationships.

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

Catheter ablation appears better than drug therapy for treating atrial fibrillation (AFib) in racial and ethnic minorities, according to a new look at CABANA trial data.

CABANA, which was undertaken to compare catheter ablation and rate-control or rhythm-control drug therapy for AFib, concluded there was no significant difference between the two strategies in improving the trial’s composite primary outcome of death, disabling stroke, serious bleeding, or cardiac arrest.

But a closer look at a subgroup of participants reveals an important difference in outcome among racial and ethnic minorities.

In that group, which made up about 10% of the CABANA study population, catheter ablation was significantly better at treating AFib than was drug therapy, producing roughly a 70% relative reduction in the primary endpoint and all-cause mortality.

The benefit for catheter ablation, which was not seen in the nonminority participants, appeared to be due to worse outcomes with drug therapy, the investigators report in an article published July 5 in the Journal of the American College of Cardiology.

“The study really highlights the importance of trying to secure an inclusive and diverse population in clinical trials,” lead author Kevin L. Thomas, MD, Duke University, Durham, N.C., said in an interview.

“When we focused on the racial and ethnic minorities who were included in CABANA, the findings were different. This was a surprise,” Dr. Thomas said.

“The findings from the secondary analysis of CABANA suggest that racial and ethnic minorities that are treated with drugs compared with ablation do worse,” he said. “If we can validate this in a larger sample of patients and this does in fact turn out to be true, then we would change how we practice medicine. We would have discussions with these populations about the benefits of ablation over drugs, and this would be important information to help guide our practice.”

The investigators analyzed data from 1,280 participants enrolled in the North American arm of CABANA. Of these, 127 (9.9%) were of racial or ethnic minorities, as defined by the National Institutes of Health, and were randomly assigned to receive ablation (n = 62) or drug therapy (n = 65).

Compared with nonminorities, participants of racial and ethnic minorities were younger (median age, 65.5 years, vs. 68.5 years) and were more likely to have NYHA functional class greater than or equal to II symptoms (37.0% vs. 22.0%), hypertension (92.1% vs. 76.8%), and an ejection fraction less than 40% (20.8% vs. 7.1%).

The overall median follow-up was 54.9 months. Among ethnic and minority participants, the median follow-up was 48 months, compared with 55.5 months for the nonminority participants.

Although there was no significant difference in the primary composite endpoint in the main CABANA trial, among racial and ethnic minorities treated with ablation, there was a 68% relative reduction in the trial’s primary endpoint (adjusted hazard ratio, 0.32; 95% confidence interval, 0.13-0.78) and a 72% relative reduction in all-cause mortality (aHR, 0.28; 95% CI, 0.10-0.79).

The 4-year Kaplan-Meier primary event rates were similar in both racial/ethnic minority and nonminority groups that received catheter ablation (12.3% vs. 9.9%).

However, the 4-year event rate was much higher among nonminority participants than among racial and ethnic minorities who received drug therapy (27.4% vs. 9.4%).

The corresponding all-cause 4-year mortality rates were 8.1% and 6.7%, respectively, in the ablation arm and 20.2% and 4.5%, respectively, in the drug arm.

Dr. Thomas and colleagues point out that heart failure in racial and ethnic minorities, particularly Black patients, is typically due to hypertensive heart disease, whereas in non-Hispanic White patients, it is overwhelmingly associated with coronary artery disease. “Our results in CABANA, therefore, raise the possibility that the variations in the prevalence of the heart diseases associated with AFib might account for differences in the benefits observed with ablation therapy.”

Prior data suggest that AFib in the setting of heart failure with either reduced or preserved ejection fraction has substantially better clinical outcomes with ablation versus drug therapy, but most studies either do not report racial/ethnic demographics or enroll very low numbers of minorities, they note.

Andrea M. Russo, MD, a professor of medicine at Rowan University, Camden, New Jersey, asks why drug therapy might result in worse outcomes in racial and ethnic minorities in an accompanying editorial.

“Those who received ablation did better than those who received drugs, and the main reason for that is not that ablation works better in minorities than nonminorities, it’s because drugs are worse in minority patients than they are in nonminority patients. This means that either the way we are using the drugs or the ones that we are using in minority patients are resulting in worse overall outcomes,” Dr. Russo told this news organization.

“The minority patients were younger and yet had more hypertension at baseline. There could be all kinds of factors contributing to their health,” she said.

Dr. Russo agrees with Dr. Thomas on the need to enroll diverse populations in clinical trials.

“Dr. Thomas should be commended. He did a fabulous job of looking at this issue. It’s only 10% of the group, but it is better than what we have had so far, and this is a start,” Dr. Russo said. “It’s bringing recognition to how important it is to make sure that we include underrepresented populations in these trials and also that we offer all appropriate therapies to everyone.”

Dr. Thomas reports financial relationships with Janssen, Pfizer, Biosense Webster. Dr. Russo reports no relevant financial relationships. The study was funded by the National Institutes of Health, St. Jude Medical Foundation and Corporation, Biosense Webster, Medtronic, and Boston Scientific.

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

Catheter ablation appears better than drug therapy for treating atrial fibrillation (AFib) in racial and ethnic minorities, according to a new look at CABANA trial data.

CABANA, which was undertaken to compare catheter ablation and rate-control or rhythm-control drug therapy for AFib, concluded there was no significant difference between the two strategies in improving the trial’s composite primary outcome of death, disabling stroke, serious bleeding, or cardiac arrest.

But a closer look at a subgroup of participants reveals an important difference in outcome among racial and ethnic minorities.

In that group, which made up about 10% of the CABANA study population, catheter ablation was significantly better at treating AFib than was drug therapy, producing roughly a 70% relative reduction in the primary endpoint and all-cause mortality.

The benefit for catheter ablation, which was not seen in the nonminority participants, appeared to be due to worse outcomes with drug therapy, the investigators report in an article published July 5 in the Journal of the American College of Cardiology.

“The study really highlights the importance of trying to secure an inclusive and diverse population in clinical trials,” lead author Kevin L. Thomas, MD, Duke University, Durham, N.C., said in an interview.

“When we focused on the racial and ethnic minorities who were included in CABANA, the findings were different. This was a surprise,” Dr. Thomas said.

“The findings from the secondary analysis of CABANA suggest that racial and ethnic minorities that are treated with drugs compared with ablation do worse,” he said. “If we can validate this in a larger sample of patients and this does in fact turn out to be true, then we would change how we practice medicine. We would have discussions with these populations about the benefits of ablation over drugs, and this would be important information to help guide our practice.”

The investigators analyzed data from 1,280 participants enrolled in the North American arm of CABANA. Of these, 127 (9.9%) were of racial or ethnic minorities, as defined by the National Institutes of Health, and were randomly assigned to receive ablation (n = 62) or drug therapy (n = 65).

Compared with nonminorities, participants of racial and ethnic minorities were younger (median age, 65.5 years, vs. 68.5 years) and were more likely to have NYHA functional class greater than or equal to II symptoms (37.0% vs. 22.0%), hypertension (92.1% vs. 76.8%), and an ejection fraction less than 40% (20.8% vs. 7.1%).

The overall median follow-up was 54.9 months. Among ethnic and minority participants, the median follow-up was 48 months, compared with 55.5 months for the nonminority participants.

Although there was no significant difference in the primary composite endpoint in the main CABANA trial, among racial and ethnic minorities treated with ablation, there was a 68% relative reduction in the trial’s primary endpoint (adjusted hazard ratio, 0.32; 95% confidence interval, 0.13-0.78) and a 72% relative reduction in all-cause mortality (aHR, 0.28; 95% CI, 0.10-0.79).

The 4-year Kaplan-Meier primary event rates were similar in both racial/ethnic minority and nonminority groups that received catheter ablation (12.3% vs. 9.9%).

However, the 4-year event rate was much higher among nonminority participants than among racial and ethnic minorities who received drug therapy (27.4% vs. 9.4%).

The corresponding all-cause 4-year mortality rates were 8.1% and 6.7%, respectively, in the ablation arm and 20.2% and 4.5%, respectively, in the drug arm.

Dr. Thomas and colleagues point out that heart failure in racial and ethnic minorities, particularly Black patients, is typically due to hypertensive heart disease, whereas in non-Hispanic White patients, it is overwhelmingly associated with coronary artery disease. “Our results in CABANA, therefore, raise the possibility that the variations in the prevalence of the heart diseases associated with AFib might account for differences in the benefits observed with ablation therapy.”

Prior data suggest that AFib in the setting of heart failure with either reduced or preserved ejection fraction has substantially better clinical outcomes with ablation versus drug therapy, but most studies either do not report racial/ethnic demographics or enroll very low numbers of minorities, they note.

Andrea M. Russo, MD, a professor of medicine at Rowan University, Camden, New Jersey, asks why drug therapy might result in worse outcomes in racial and ethnic minorities in an accompanying editorial.

“Those who received ablation did better than those who received drugs, and the main reason for that is not that ablation works better in minorities than nonminorities, it’s because drugs are worse in minority patients than they are in nonminority patients. This means that either the way we are using the drugs or the ones that we are using in minority patients are resulting in worse overall outcomes,” Dr. Russo told this news organization.

“The minority patients were younger and yet had more hypertension at baseline. There could be all kinds of factors contributing to their health,” she said.

Dr. Russo agrees with Dr. Thomas on the need to enroll diverse populations in clinical trials.

“Dr. Thomas should be commended. He did a fabulous job of looking at this issue. It’s only 10% of the group, but it is better than what we have had so far, and this is a start,” Dr. Russo said. “It’s bringing recognition to how important it is to make sure that we include underrepresented populations in these trials and also that we offer all appropriate therapies to everyone.”

Dr. Thomas reports financial relationships with Janssen, Pfizer, Biosense Webster. Dr. Russo reports no relevant financial relationships. The study was funded by the National Institutes of Health, St. Jude Medical Foundation and Corporation, Biosense Webster, Medtronic, and Boston Scientific.

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

Catheter ablation appears better than drug therapy for treating atrial fibrillation (AFib) in racial and ethnic minorities, according to a new look at CABANA trial data.

CABANA, which was undertaken to compare catheter ablation and rate-control or rhythm-control drug therapy for AFib, concluded there was no significant difference between the two strategies in improving the trial’s composite primary outcome of death, disabling stroke, serious bleeding, or cardiac arrest.

But a closer look at a subgroup of participants reveals an important difference in outcome among racial and ethnic minorities.

In that group, which made up about 10% of the CABANA study population, catheter ablation was significantly better at treating AFib than was drug therapy, producing roughly a 70% relative reduction in the primary endpoint and all-cause mortality.

The benefit for catheter ablation, which was not seen in the nonminority participants, appeared to be due to worse outcomes with drug therapy, the investigators report in an article published July 5 in the Journal of the American College of Cardiology.

“The study really highlights the importance of trying to secure an inclusive and diverse population in clinical trials,” lead author Kevin L. Thomas, MD, Duke University, Durham, N.C., said in an interview.

“When we focused on the racial and ethnic minorities who were included in CABANA, the findings were different. This was a surprise,” Dr. Thomas said.

“The findings from the secondary analysis of CABANA suggest that racial and ethnic minorities that are treated with drugs compared with ablation do worse,” he said. “If we can validate this in a larger sample of patients and this does in fact turn out to be true, then we would change how we practice medicine. We would have discussions with these populations about the benefits of ablation over drugs, and this would be important information to help guide our practice.”

The investigators analyzed data from 1,280 participants enrolled in the North American arm of CABANA. Of these, 127 (9.9%) were of racial or ethnic minorities, as defined by the National Institutes of Health, and were randomly assigned to receive ablation (n = 62) or drug therapy (n = 65).

Compared with nonminorities, participants of racial and ethnic minorities were younger (median age, 65.5 years, vs. 68.5 years) and were more likely to have NYHA functional class greater than or equal to II symptoms (37.0% vs. 22.0%), hypertension (92.1% vs. 76.8%), and an ejection fraction less than 40% (20.8% vs. 7.1%).

The overall median follow-up was 54.9 months. Among ethnic and minority participants, the median follow-up was 48 months, compared with 55.5 months for the nonminority participants.

Although there was no significant difference in the primary composite endpoint in the main CABANA trial, among racial and ethnic minorities treated with ablation, there was a 68% relative reduction in the trial’s primary endpoint (adjusted hazard ratio, 0.32; 95% confidence interval, 0.13-0.78) and a 72% relative reduction in all-cause mortality (aHR, 0.28; 95% CI, 0.10-0.79).

The 4-year Kaplan-Meier primary event rates were similar in both racial/ethnic minority and nonminority groups that received catheter ablation (12.3% vs. 9.9%).

However, the 4-year event rate was much higher among nonminority participants than among racial and ethnic minorities who received drug therapy (27.4% vs. 9.4%).

The corresponding all-cause 4-year mortality rates were 8.1% and 6.7%, respectively, in the ablation arm and 20.2% and 4.5%, respectively, in the drug arm.

Dr. Thomas and colleagues point out that heart failure in racial and ethnic minorities, particularly Black patients, is typically due to hypertensive heart disease, whereas in non-Hispanic White patients, it is overwhelmingly associated with coronary artery disease. “Our results in CABANA, therefore, raise the possibility that the variations in the prevalence of the heart diseases associated with AFib might account for differences in the benefits observed with ablation therapy.”

Prior data suggest that AFib in the setting of heart failure with either reduced or preserved ejection fraction has substantially better clinical outcomes with ablation versus drug therapy, but most studies either do not report racial/ethnic demographics or enroll very low numbers of minorities, they note.

Andrea M. Russo, MD, a professor of medicine at Rowan University, Camden, New Jersey, asks why drug therapy might result in worse outcomes in racial and ethnic minorities in an accompanying editorial.

“Those who received ablation did better than those who received drugs, and the main reason for that is not that ablation works better in minorities than nonminorities, it’s because drugs are worse in minority patients than they are in nonminority patients. This means that either the way we are using the drugs or the ones that we are using in minority patients are resulting in worse overall outcomes,” Dr. Russo told this news organization.

“The minority patients were younger and yet had more hypertension at baseline. There could be all kinds of factors contributing to their health,” she said.

Dr. Russo agrees with Dr. Thomas on the need to enroll diverse populations in clinical trials.

“Dr. Thomas should be commended. He did a fabulous job of looking at this issue. It’s only 10% of the group, but it is better than what we have had so far, and this is a start,” Dr. Russo said. “It’s bringing recognition to how important it is to make sure that we include underrepresented populations in these trials and also that we offer all appropriate therapies to everyone.”

Dr. Thomas reports financial relationships with Janssen, Pfizer, Biosense Webster. Dr. Russo reports no relevant financial relationships. The study was funded by the National Institutes of Health, St. Jude Medical Foundation and Corporation, Biosense Webster, Medtronic, and Boston Scientific.

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

Midlife changes in wealth may affect a patient’s risk of cardiovascular disease, a new cohort study suggests.

It found that upward wealth mobility relative to peers was independently associated with protection against cardiovascular disease after age 65. In contrast, downward wealth mobility during middle age was linked to an increased risk of adverse cardiovascular events.

“A lot of studies have shown an inverse relationship between wealth and health in cross section at a single timepoint. What we really wanted to understand is whether this risk is modifiable and if this relationship changes over time,” senior author Muthiah Vaduganathan, MD, MPH, Brigham and Women’s Hospital Heart & Vascular Center, Boston, said in an interview.

The results were published online June 15 in JAMA Cardiology.  

For the primary analysis, the researchers collected data from 5,579 U.S. adults aged 50 years and older with no known cardiovascular disease at baseline who participated in the RAND Health and Retirement Study, a longitudinal survey that measures changes in health and wealth every 2 years. The participants had been interviewed in at least two of three 5-year age intervals (50-54, 55-59, 60-64 years) and had follow-up data available after age 65. Survey data from Jan. 1, 1992 to Dec. 31, 2016 was used.

Participants were grouped into quintiles based on wealth, defined as total nonhousing assets in 2012 U.S. dollars, and were further stratified by birth cohort (1931-1935, 1936-1940, 1941-1945, 1946-1950). Upward relative wealth mobility involved an increase of one or more wealth quintiles during the observation period, while downward relative wealth mobility was defined as a decrease of one or more wealth quintiles. Participants who remained in the same quintile were described as having stable wealth.

Across the birth cohorts, the bottom wealth quintile ranged from -$581,447 to $7,460 and the top wealth quintile ranged from $327,064 to $22,661,450.

Over a mean 16.9 years of follow-up, the primary outcome of cardiovascular death or a nonfatal cardiovascular event such as a heart attack or stroke occurred in 1,336 participants, including 22.5% whose wealth increased by one quintile versus 28.1% whose wealth decreased by one quintile.

In adjusted analyses, higher initial wealth was associated with lower cardiovascular risk after turning 65 (adjusted hazard ratio per quintile, 0.89; 95% confidence interval, 0.84-0.95; P = .001). Additionally, experiencing relative upward wealth mobility by at least one quintile was independently associated with a lower risk of a nonfatal cardiovascular event or cardiovascular death, compared with stable wealth (aHR, 0.84; 95% CI, 0.73-0.97; P = .02).

Downward wealth mobility was associated with worse cardiovascular outcomes (aHR, 1.15; 95% CI, 1.00-1.32; P = .046). This effect was also observed on the risk of cardiovascular death in a secondary analysis of 3,360 participants who had a previous history of cardiovascular disease (aHR, 1.48; 95% CI, 1.13-1.93; P = .004).

“We estimate that each $100,000 increase in wealth was associated with a roughly 1% lower hazard of cardiovascular outcome in follow-up,” the authors write.

The protective effect of wealth on cardiovascular health may be the result of factors such as “better access to care, having more time to adhere to a healthier diet or exercise regularly, and reduced stress,” Kiarri Kershaw, PhD, a social epidemiologist at Northwestern University, Chicago, said in an interview. Dr. Kershaw, who was not involved in the study, added that “stress can affect health through both biological and behavioral pathways.”

The study did not find a statistical relationship between race, wealth, and health. However, it was observed that the overall risk of cardiovascular events among non-Hispanic Black and Black participants was lower. The authors noted that “these findings are likely a byproduct of collider bias, in which Black and Hispanic participants who experience downward wealth mobility are more likely to experience barriers to care and subsequently less likely to receive a diagnosis of cardiovascular disease.”

Moving forward, the researchers plan to investigate health policy interventions that “best promote and sustain economic opportunity and wealth formed among low-income individuals,” Dr. Vaduganathan said.

The study was funded independently. Dr. Vaduganathan and Dr. Kershaw have disclosed no relevant financial relationships.

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

Midlife changes in wealth may affect a patient’s risk of cardiovascular disease, a new cohort study suggests.

It found that upward wealth mobility relative to peers was independently associated with protection against cardiovascular disease after age 65. In contrast, downward wealth mobility during middle age was linked to an increased risk of adverse cardiovascular events.

“A lot of studies have shown an inverse relationship between wealth and health in cross section at a single timepoint. What we really wanted to understand is whether this risk is modifiable and if this relationship changes over time,” senior author Muthiah Vaduganathan, MD, MPH, Brigham and Women’s Hospital Heart & Vascular Center, Boston, said in an interview.

The results were published online June 15 in JAMA Cardiology.  

For the primary analysis, the researchers collected data from 5,579 U.S. adults aged 50 years and older with no known cardiovascular disease at baseline who participated in the RAND Health and Retirement Study, a longitudinal survey that measures changes in health and wealth every 2 years. The participants had been interviewed in at least two of three 5-year age intervals (50-54, 55-59, 60-64 years) and had follow-up data available after age 65. Survey data from Jan. 1, 1992 to Dec. 31, 2016 was used.

Participants were grouped into quintiles based on wealth, defined as total nonhousing assets in 2012 U.S. dollars, and were further stratified by birth cohort (1931-1935, 1936-1940, 1941-1945, 1946-1950). Upward relative wealth mobility involved an increase of one or more wealth quintiles during the observation period, while downward relative wealth mobility was defined as a decrease of one or more wealth quintiles. Participants who remained in the same quintile were described as having stable wealth.

Across the birth cohorts, the bottom wealth quintile ranged from -$581,447 to $7,460 and the top wealth quintile ranged from $327,064 to $22,661,450.

Over a mean 16.9 years of follow-up, the primary outcome of cardiovascular death or a nonfatal cardiovascular event such as a heart attack or stroke occurred in 1,336 participants, including 22.5% whose wealth increased by one quintile versus 28.1% whose wealth decreased by one quintile.

In adjusted analyses, higher initial wealth was associated with lower cardiovascular risk after turning 65 (adjusted hazard ratio per quintile, 0.89; 95% confidence interval, 0.84-0.95; P = .001). Additionally, experiencing relative upward wealth mobility by at least one quintile was independently associated with a lower risk of a nonfatal cardiovascular event or cardiovascular death, compared with stable wealth (aHR, 0.84; 95% CI, 0.73-0.97; P = .02).

Downward wealth mobility was associated with worse cardiovascular outcomes (aHR, 1.15; 95% CI, 1.00-1.32; P = .046). This effect was also observed on the risk of cardiovascular death in a secondary analysis of 3,360 participants who had a previous history of cardiovascular disease (aHR, 1.48; 95% CI, 1.13-1.93; P = .004).

“We estimate that each $100,000 increase in wealth was associated with a roughly 1% lower hazard of cardiovascular outcome in follow-up,” the authors write.

The protective effect of wealth on cardiovascular health may be the result of factors such as “better access to care, having more time to adhere to a healthier diet or exercise regularly, and reduced stress,” Kiarri Kershaw, PhD, a social epidemiologist at Northwestern University, Chicago, said in an interview. Dr. Kershaw, who was not involved in the study, added that “stress can affect health through both biological and behavioral pathways.”

The study did not find a statistical relationship between race, wealth, and health. However, it was observed that the overall risk of cardiovascular events among non-Hispanic Black and Black participants was lower. The authors noted that “these findings are likely a byproduct of collider bias, in which Black and Hispanic participants who experience downward wealth mobility are more likely to experience barriers to care and subsequently less likely to receive a diagnosis of cardiovascular disease.”

Moving forward, the researchers plan to investigate health policy interventions that “best promote and sustain economic opportunity and wealth formed among low-income individuals,” Dr. Vaduganathan said.

The study was funded independently. Dr. Vaduganathan and Dr. Kershaw have disclosed no relevant financial relationships.

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

Midlife changes in wealth may affect a patient’s risk of cardiovascular disease, a new cohort study suggests.

It found that upward wealth mobility relative to peers was independently associated with protection against cardiovascular disease after age 65. In contrast, downward wealth mobility during middle age was linked to an increased risk of adverse cardiovascular events.

“A lot of studies have shown an inverse relationship between wealth and health in cross section at a single timepoint. What we really wanted to understand is whether this risk is modifiable and if this relationship changes over time,” senior author Muthiah Vaduganathan, MD, MPH, Brigham and Women’s Hospital Heart & Vascular Center, Boston, said in an interview.

The results were published online June 15 in JAMA Cardiology.  

For the primary analysis, the researchers collected data from 5,579 U.S. adults aged 50 years and older with no known cardiovascular disease at baseline who participated in the RAND Health and Retirement Study, a longitudinal survey that measures changes in health and wealth every 2 years. The participants had been interviewed in at least two of three 5-year age intervals (50-54, 55-59, 60-64 years) and had follow-up data available after age 65. Survey data from Jan. 1, 1992 to Dec. 31, 2016 was used.

Participants were grouped into quintiles based on wealth, defined as total nonhousing assets in 2012 U.S. dollars, and were further stratified by birth cohort (1931-1935, 1936-1940, 1941-1945, 1946-1950). Upward relative wealth mobility involved an increase of one or more wealth quintiles during the observation period, while downward relative wealth mobility was defined as a decrease of one or more wealth quintiles. Participants who remained in the same quintile were described as having stable wealth.

Across the birth cohorts, the bottom wealth quintile ranged from -$581,447 to $7,460 and the top wealth quintile ranged from $327,064 to $22,661,450.

Over a mean 16.9 years of follow-up, the primary outcome of cardiovascular death or a nonfatal cardiovascular event such as a heart attack or stroke occurred in 1,336 participants, including 22.5% whose wealth increased by one quintile versus 28.1% whose wealth decreased by one quintile.

In adjusted analyses, higher initial wealth was associated with lower cardiovascular risk after turning 65 (adjusted hazard ratio per quintile, 0.89; 95% confidence interval, 0.84-0.95; P = .001). Additionally, experiencing relative upward wealth mobility by at least one quintile was independently associated with a lower risk of a nonfatal cardiovascular event or cardiovascular death, compared with stable wealth (aHR, 0.84; 95% CI, 0.73-0.97; P = .02).

Downward wealth mobility was associated with worse cardiovascular outcomes (aHR, 1.15; 95% CI, 1.00-1.32; P = .046). This effect was also observed on the risk of cardiovascular death in a secondary analysis of 3,360 participants who had a previous history of cardiovascular disease (aHR, 1.48; 95% CI, 1.13-1.93; P = .004).

“We estimate that each $100,000 increase in wealth was associated with a roughly 1% lower hazard of cardiovascular outcome in follow-up,” the authors write.

The protective effect of wealth on cardiovascular health may be the result of factors such as “better access to care, having more time to adhere to a healthier diet or exercise regularly, and reduced stress,” Kiarri Kershaw, PhD, a social epidemiologist at Northwestern University, Chicago, said in an interview. Dr. Kershaw, who was not involved in the study, added that “stress can affect health through both biological and behavioral pathways.”

The study did not find a statistical relationship between race, wealth, and health. However, it was observed that the overall risk of cardiovascular events among non-Hispanic Black and Black participants was lower. The authors noted that “these findings are likely a byproduct of collider bias, in which Black and Hispanic participants who experience downward wealth mobility are more likely to experience barriers to care and subsequently less likely to receive a diagnosis of cardiovascular disease.”

Moving forward, the researchers plan to investigate health policy interventions that “best promote and sustain economic opportunity and wealth formed among low-income individuals,” Dr. Vaduganathan said.

The study was funded independently. Dr. Vaduganathan and Dr. Kershaw have disclosed no relevant financial relationships.

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