Mitchel is a reporter for MDedge based in the Philadelphia area. He started with the company in 1992, when it was International Medical News Group (IMNG), and has since covered a range of medical specialties. Mitchel trained as a virologist at Roswell Park Memorial Institute in Buffalo, and then worked briefly as a researcher at Boston Children's Hospital before pivoting to journalism as a AAAS Mass Media Fellow in 1980. His first reporting job was with Science Digest magazine, and from the mid-1980s to early-1990s he was a reporter with Medical World News. @mitchelzoler

AHA updates management when CAD and T2DM coincide

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Tue, 05/03/2022 - 15:10

Patients with stable coronary artery disease and type 2 diabetes mellitus could benefit from a “plethora of newly available risk-reduction strategies,” but their “adoption into clinical practice has been slow” and inconsistent, prompting an expert panel organized by the American Heart Association to collate the range of treatment recommendations now applicable to this patient population in a scientific statement released on April 13.

Dr. Suzanne Arnold

“There are a number of things to consider when treating patients with stable coronary artery disease [CAD] and type 2 diabetes mellitus [T2DM], with new medications and trials and data emerging. It’s difficult to keep up with all of the complexities,” which was why the Association’s Councils on Lifestyle and Cardiometabolic Health and on Clinical Cardiology put together a writing group to summarize and prioritize the range of lifestyle, medical, and interventional options that now require consideration and potential use on patients managed in routine practice, explained Suzanne V. Arnold, MD, chair of the writing group, in an interview.

The new scientific statement (Circulation. 2020 Apr 13; doi: 10.1161/CIR.0000000000000766), aimed primarily at cardiologists but also intended to inform primary care physicians, endocrinologists, and all other clinicians who deal with these patients, pulls together “everything someone needs to think about if they care for patients with CAD and T2DM,” said Deepak L. Bhatt, MD, professor of medicine at Harvard Medical School in Boston and vice chair of the statement-writing panel in an interview. “There is a lot to know,” he added.

The statement covers antithrombotic therapies; blood pressure control, with a discussion of both the appropriate pressure goal and the best drug types used to reach it; lipid management; glycemic control; lifestyle modification; weight management, including the role of bariatric surgery; and approaches to managing stable angina, both medically and with revascularization.

Dr. Deepak L. Bhatt

“The goal was to give clinicians a good sense of what new treatments they should consider” for these patients, said Dr. Bhatt, who is also director of interventional cardiovascular programs at Brigham and Women’s Hospital, also in Boston. Because of the tight associations between T2DM and cardiovascular disease in general including CAD, “cardiologists are increasingly involved in managing patients with T2DM,” he noted. The statement gives a comprehensive overview and critical assessment of the management of these patients as of the end of 2019 as a consensus from a panel of 11 experts .

The statement also stressed that “substantial portions of patients with T2DM and CAD, including those after an acute coronary syndrome, do not receive therapies with proven cardiovascular benefit, such as high-intensity statins, dual-antiplatelet therapy, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, and glucose-lowering agents with proven cardiovascular benefits.

“These gaps in care highlight a critical opportunity for cardiovascular specialists to assume a more active role in the collaborative care of patients with T2DM and CAD,” the statement said. This includes “encouraging cardiologists to become more active in the selection of glucose-lowering medications” for these patients because it could “really move the needle,” said Dr. Arnold, a cardiologist with Saint Luke’s Health System in Kansas City, Mo. She was referring specifically to broader reliance on both the SGTL2 (sodium-glucose cotransporter 2) inhibitors and the GLP-1 (glucagonlike peptide-1) receptor agonists as top choices for controlling hyperglycemia. Based on recent evidence drugs in these two classes “could be considered first line for patients with T2DM and CAD, and would likely be preferred over metformin,” Dr. Arnold said in an interview. Although the statement identified the SGLT2 inhibitors as “the first drug class [for glycemic control] to show clear benefits on cardiovascular outcomes,” it does not explicitly label the class first-line and it also skirts that designation for the GLP-1 receptor agonist class, while noting that metformin “remains the drug most frequently recommended as first-line therapy in treatment guidelines.”

“I wouldn’t disagree with someone who said that SGLT2 inhibitors and GLP-1 receptor agonists are first line,” but prescribing patterns also depend on familiarity, cost, and access, noted Dr. Bhatt, which can all be issues with agents from these classes compared with metformin, a widely available generic with decades of use. “Metformin is safe and cheap, so we did not want to discount it,” said Dr. Arnold. Dr. Bhatt recently coauthored an editorial that gave an enthusiastic endorsement to using SGLT2 inhibitors in patients with diabetes (Cell Metab. 2019 Nov 5;30[5]:47-9).

Another notable feature of the statement is the potential it assigns to bariatric surgery as a management tool with documented safety and efficacy for improving cardiovascular risk factors. However, the statement also notes that randomized trials “have thus far been inadequately powered to assess cardiovascular events and mortality, although observational studies have consistently shown cardiovascular risk reduction with such procedures.” The statement continues that despite potential cardiovascular benefits “bariatric surgery remains underused among eligible patients,” and said that surgery performed as Roux-en-Y bypass or sleeve gastrectomy “may be another effective tool for cardiovascular risk reduction in the subset of patients with obesity,” particularly patients with a body mass index of at least 35 kg/m2.

“While the percentage of patients who are optimal for bariatric surgery is not known, the most recent NHANES [National Health and Nutrition Examination Study] study showed that less than 0.5% of eligible patients underwent bariatric surgery,” Dr. Arnold noted. Bariatric surgery is “certainly not a recommendation for everyone, or even a majority of patients, but bariatric surgery should be on our radar,” for patients with CAD and T2DM, she said.

Right now, “few cardiologists think about bariatric surgery,” as a treatment option, but study results have shown that “in carefully selected patients treated by skilled surgeons at high-volume centers, patients will do better with bariatric surgery than with best medical therapy for improvements in multiple risk factors, including glycemic control,” Dr. Bhatt said in the interview. “It’s not first-line treatment, but it’s an option to consider,” he added, while also noting that bariatric surgery is most beneficial to patients relatively early in the course of T2DM, when its been in place for just a few years rather than a couple of decades.

The statement also notably included a “first-line” call out for icosapent ethyl (Vascepa), a novel agent approved in December 2019 for routine use in U.S. patients, including those with CAD and T2DM as long as their blood triglyceride level was at least 150 mg/dL. Dr. Bhatt, who led the REDUCE-IT study that was pivotal for proving the safety and efficacy of icosapent ethyl (N Engl J Med. 2019 Jan 3;380[1]:11-22), estimated that anywhere from 15% to as many as half the patients with CAD and T2DM might have a triglyceride level that would allow them to receive icosapent ethyl. One population-based study in Canada of nearly 200,000 people with atherosclerotic cardiovascular disease found a 25% prevalence of the triglyceride level needed to qualify to receive icosapent ethyl under current labeling, he noted (Eur Heart J. 2020 Jan 1;41[1]:86-94). However, the FDA label does not specify that triglycerides be measured when fasting, and a nonfasting level of about 150 mg/dL will likely appear for patients with fasting levels that fall as low as about 100 mg/dL, Dr. Bhatt said. He hoped that future studies will assess the efficacy of icosapent ethyl in patients with even lower triglyceride levels.

Other sections of the statement also recommend that clinicians: Target long-term dual-antiplatelet therapy to CAD and T2DM patients with additional high-risk markers such as prior MI, younger age, and tobacco use; prescribe a low-dose oral anticoagulant along with an antiplatelet drug such as aspirin for secondary-prevention patients; promote a blood pressure target of less than 140/90 mm Hg for all CAD and T2DM patients and apply a goal of less than 130/80 mm Hg in higher-risk patients such as blacks, Asians, and those with cerebrovascular disease; and reassure patients that “despite a modest increase in blood sugars, the risk-benefit ratio is clearly in favor of administering statins to people with T2DM and CAD.”

Dr. Arnold had no disclosures. Dr. Bhatt has been an adviser to Cardax, Cereno Scientific, Medscape Cardiology, PhaseBio; PLx Pharma, and Regado Biosciences, and he has received research funding from numerous companies including Amarin, the company that markets icosapent ethyl.

 

 

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Patients with stable coronary artery disease and type 2 diabetes mellitus could benefit from a “plethora of newly available risk-reduction strategies,” but their “adoption into clinical practice has been slow” and inconsistent, prompting an expert panel organized by the American Heart Association to collate the range of treatment recommendations now applicable to this patient population in a scientific statement released on April 13.

Dr. Suzanne Arnold

“There are a number of things to consider when treating patients with stable coronary artery disease [CAD] and type 2 diabetes mellitus [T2DM], with new medications and trials and data emerging. It’s difficult to keep up with all of the complexities,” which was why the Association’s Councils on Lifestyle and Cardiometabolic Health and on Clinical Cardiology put together a writing group to summarize and prioritize the range of lifestyle, medical, and interventional options that now require consideration and potential use on patients managed in routine practice, explained Suzanne V. Arnold, MD, chair of the writing group, in an interview.

The new scientific statement (Circulation. 2020 Apr 13; doi: 10.1161/CIR.0000000000000766), aimed primarily at cardiologists but also intended to inform primary care physicians, endocrinologists, and all other clinicians who deal with these patients, pulls together “everything someone needs to think about if they care for patients with CAD and T2DM,” said Deepak L. Bhatt, MD, professor of medicine at Harvard Medical School in Boston and vice chair of the statement-writing panel in an interview. “There is a lot to know,” he added.

The statement covers antithrombotic therapies; blood pressure control, with a discussion of both the appropriate pressure goal and the best drug types used to reach it; lipid management; glycemic control; lifestyle modification; weight management, including the role of bariatric surgery; and approaches to managing stable angina, both medically and with revascularization.

Dr. Deepak L. Bhatt

“The goal was to give clinicians a good sense of what new treatments they should consider” for these patients, said Dr. Bhatt, who is also director of interventional cardiovascular programs at Brigham and Women’s Hospital, also in Boston. Because of the tight associations between T2DM and cardiovascular disease in general including CAD, “cardiologists are increasingly involved in managing patients with T2DM,” he noted. The statement gives a comprehensive overview and critical assessment of the management of these patients as of the end of 2019 as a consensus from a panel of 11 experts .

The statement also stressed that “substantial portions of patients with T2DM and CAD, including those after an acute coronary syndrome, do not receive therapies with proven cardiovascular benefit, such as high-intensity statins, dual-antiplatelet therapy, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, and glucose-lowering agents with proven cardiovascular benefits.

“These gaps in care highlight a critical opportunity for cardiovascular specialists to assume a more active role in the collaborative care of patients with T2DM and CAD,” the statement said. This includes “encouraging cardiologists to become more active in the selection of glucose-lowering medications” for these patients because it could “really move the needle,” said Dr. Arnold, a cardiologist with Saint Luke’s Health System in Kansas City, Mo. She was referring specifically to broader reliance on both the SGTL2 (sodium-glucose cotransporter 2) inhibitors and the GLP-1 (glucagonlike peptide-1) receptor agonists as top choices for controlling hyperglycemia. Based on recent evidence drugs in these two classes “could be considered first line for patients with T2DM and CAD, and would likely be preferred over metformin,” Dr. Arnold said in an interview. Although the statement identified the SGLT2 inhibitors as “the first drug class [for glycemic control] to show clear benefits on cardiovascular outcomes,” it does not explicitly label the class first-line and it also skirts that designation for the GLP-1 receptor agonist class, while noting that metformin “remains the drug most frequently recommended as first-line therapy in treatment guidelines.”

“I wouldn’t disagree with someone who said that SGLT2 inhibitors and GLP-1 receptor agonists are first line,” but prescribing patterns also depend on familiarity, cost, and access, noted Dr. Bhatt, which can all be issues with agents from these classes compared with metformin, a widely available generic with decades of use. “Metformin is safe and cheap, so we did not want to discount it,” said Dr. Arnold. Dr. Bhatt recently coauthored an editorial that gave an enthusiastic endorsement to using SGLT2 inhibitors in patients with diabetes (Cell Metab. 2019 Nov 5;30[5]:47-9).

Another notable feature of the statement is the potential it assigns to bariatric surgery as a management tool with documented safety and efficacy for improving cardiovascular risk factors. However, the statement also notes that randomized trials “have thus far been inadequately powered to assess cardiovascular events and mortality, although observational studies have consistently shown cardiovascular risk reduction with such procedures.” The statement continues that despite potential cardiovascular benefits “bariatric surgery remains underused among eligible patients,” and said that surgery performed as Roux-en-Y bypass or sleeve gastrectomy “may be another effective tool for cardiovascular risk reduction in the subset of patients with obesity,” particularly patients with a body mass index of at least 35 kg/m2.

“While the percentage of patients who are optimal for bariatric surgery is not known, the most recent NHANES [National Health and Nutrition Examination Study] study showed that less than 0.5% of eligible patients underwent bariatric surgery,” Dr. Arnold noted. Bariatric surgery is “certainly not a recommendation for everyone, or even a majority of patients, but bariatric surgery should be on our radar,” for patients with CAD and T2DM, she said.

Right now, “few cardiologists think about bariatric surgery,” as a treatment option, but study results have shown that “in carefully selected patients treated by skilled surgeons at high-volume centers, patients will do better with bariatric surgery than with best medical therapy for improvements in multiple risk factors, including glycemic control,” Dr. Bhatt said in the interview. “It’s not first-line treatment, but it’s an option to consider,” he added, while also noting that bariatric surgery is most beneficial to patients relatively early in the course of T2DM, when its been in place for just a few years rather than a couple of decades.

The statement also notably included a “first-line” call out for icosapent ethyl (Vascepa), a novel agent approved in December 2019 for routine use in U.S. patients, including those with CAD and T2DM as long as their blood triglyceride level was at least 150 mg/dL. Dr. Bhatt, who led the REDUCE-IT study that was pivotal for proving the safety and efficacy of icosapent ethyl (N Engl J Med. 2019 Jan 3;380[1]:11-22), estimated that anywhere from 15% to as many as half the patients with CAD and T2DM might have a triglyceride level that would allow them to receive icosapent ethyl. One population-based study in Canada of nearly 200,000 people with atherosclerotic cardiovascular disease found a 25% prevalence of the triglyceride level needed to qualify to receive icosapent ethyl under current labeling, he noted (Eur Heart J. 2020 Jan 1;41[1]:86-94). However, the FDA label does not specify that triglycerides be measured when fasting, and a nonfasting level of about 150 mg/dL will likely appear for patients with fasting levels that fall as low as about 100 mg/dL, Dr. Bhatt said. He hoped that future studies will assess the efficacy of icosapent ethyl in patients with even lower triglyceride levels.

Other sections of the statement also recommend that clinicians: Target long-term dual-antiplatelet therapy to CAD and T2DM patients with additional high-risk markers such as prior MI, younger age, and tobacco use; prescribe a low-dose oral anticoagulant along with an antiplatelet drug such as aspirin for secondary-prevention patients; promote a blood pressure target of less than 140/90 mm Hg for all CAD and T2DM patients and apply a goal of less than 130/80 mm Hg in higher-risk patients such as blacks, Asians, and those with cerebrovascular disease; and reassure patients that “despite a modest increase in blood sugars, the risk-benefit ratio is clearly in favor of administering statins to people with T2DM and CAD.”

Dr. Arnold had no disclosures. Dr. Bhatt has been an adviser to Cardax, Cereno Scientific, Medscape Cardiology, PhaseBio; PLx Pharma, and Regado Biosciences, and he has received research funding from numerous companies including Amarin, the company that markets icosapent ethyl.

 

 

Patients with stable coronary artery disease and type 2 diabetes mellitus could benefit from a “plethora of newly available risk-reduction strategies,” but their “adoption into clinical practice has been slow” and inconsistent, prompting an expert panel organized by the American Heart Association to collate the range of treatment recommendations now applicable to this patient population in a scientific statement released on April 13.

Dr. Suzanne Arnold

“There are a number of things to consider when treating patients with stable coronary artery disease [CAD] and type 2 diabetes mellitus [T2DM], with new medications and trials and data emerging. It’s difficult to keep up with all of the complexities,” which was why the Association’s Councils on Lifestyle and Cardiometabolic Health and on Clinical Cardiology put together a writing group to summarize and prioritize the range of lifestyle, medical, and interventional options that now require consideration and potential use on patients managed in routine practice, explained Suzanne V. Arnold, MD, chair of the writing group, in an interview.

The new scientific statement (Circulation. 2020 Apr 13; doi: 10.1161/CIR.0000000000000766), aimed primarily at cardiologists but also intended to inform primary care physicians, endocrinologists, and all other clinicians who deal with these patients, pulls together “everything someone needs to think about if they care for patients with CAD and T2DM,” said Deepak L. Bhatt, MD, professor of medicine at Harvard Medical School in Boston and vice chair of the statement-writing panel in an interview. “There is a lot to know,” he added.

The statement covers antithrombotic therapies; blood pressure control, with a discussion of both the appropriate pressure goal and the best drug types used to reach it; lipid management; glycemic control; lifestyle modification; weight management, including the role of bariatric surgery; and approaches to managing stable angina, both medically and with revascularization.

Dr. Deepak L. Bhatt

“The goal was to give clinicians a good sense of what new treatments they should consider” for these patients, said Dr. Bhatt, who is also director of interventional cardiovascular programs at Brigham and Women’s Hospital, also in Boston. Because of the tight associations between T2DM and cardiovascular disease in general including CAD, “cardiologists are increasingly involved in managing patients with T2DM,” he noted. The statement gives a comprehensive overview and critical assessment of the management of these patients as of the end of 2019 as a consensus from a panel of 11 experts .

The statement also stressed that “substantial portions of patients with T2DM and CAD, including those after an acute coronary syndrome, do not receive therapies with proven cardiovascular benefit, such as high-intensity statins, dual-antiplatelet therapy, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, and glucose-lowering agents with proven cardiovascular benefits.

“These gaps in care highlight a critical opportunity for cardiovascular specialists to assume a more active role in the collaborative care of patients with T2DM and CAD,” the statement said. This includes “encouraging cardiologists to become more active in the selection of glucose-lowering medications” for these patients because it could “really move the needle,” said Dr. Arnold, a cardiologist with Saint Luke’s Health System in Kansas City, Mo. She was referring specifically to broader reliance on both the SGTL2 (sodium-glucose cotransporter 2) inhibitors and the GLP-1 (glucagonlike peptide-1) receptor agonists as top choices for controlling hyperglycemia. Based on recent evidence drugs in these two classes “could be considered first line for patients with T2DM and CAD, and would likely be preferred over metformin,” Dr. Arnold said in an interview. Although the statement identified the SGLT2 inhibitors as “the first drug class [for glycemic control] to show clear benefits on cardiovascular outcomes,” it does not explicitly label the class first-line and it also skirts that designation for the GLP-1 receptor agonist class, while noting that metformin “remains the drug most frequently recommended as first-line therapy in treatment guidelines.”

“I wouldn’t disagree with someone who said that SGLT2 inhibitors and GLP-1 receptor agonists are first line,” but prescribing patterns also depend on familiarity, cost, and access, noted Dr. Bhatt, which can all be issues with agents from these classes compared with metformin, a widely available generic with decades of use. “Metformin is safe and cheap, so we did not want to discount it,” said Dr. Arnold. Dr. Bhatt recently coauthored an editorial that gave an enthusiastic endorsement to using SGLT2 inhibitors in patients with diabetes (Cell Metab. 2019 Nov 5;30[5]:47-9).

Another notable feature of the statement is the potential it assigns to bariatric surgery as a management tool with documented safety and efficacy for improving cardiovascular risk factors. However, the statement also notes that randomized trials “have thus far been inadequately powered to assess cardiovascular events and mortality, although observational studies have consistently shown cardiovascular risk reduction with such procedures.” The statement continues that despite potential cardiovascular benefits “bariatric surgery remains underused among eligible patients,” and said that surgery performed as Roux-en-Y bypass or sleeve gastrectomy “may be another effective tool for cardiovascular risk reduction in the subset of patients with obesity,” particularly patients with a body mass index of at least 35 kg/m2.

“While the percentage of patients who are optimal for bariatric surgery is not known, the most recent NHANES [National Health and Nutrition Examination Study] study showed that less than 0.5% of eligible patients underwent bariatric surgery,” Dr. Arnold noted. Bariatric surgery is “certainly not a recommendation for everyone, or even a majority of patients, but bariatric surgery should be on our radar,” for patients with CAD and T2DM, she said.

Right now, “few cardiologists think about bariatric surgery,” as a treatment option, but study results have shown that “in carefully selected patients treated by skilled surgeons at high-volume centers, patients will do better with bariatric surgery than with best medical therapy for improvements in multiple risk factors, including glycemic control,” Dr. Bhatt said in the interview. “It’s not first-line treatment, but it’s an option to consider,” he added, while also noting that bariatric surgery is most beneficial to patients relatively early in the course of T2DM, when its been in place for just a few years rather than a couple of decades.

The statement also notably included a “first-line” call out for icosapent ethyl (Vascepa), a novel agent approved in December 2019 for routine use in U.S. patients, including those with CAD and T2DM as long as their blood triglyceride level was at least 150 mg/dL. Dr. Bhatt, who led the REDUCE-IT study that was pivotal for proving the safety and efficacy of icosapent ethyl (N Engl J Med. 2019 Jan 3;380[1]:11-22), estimated that anywhere from 15% to as many as half the patients with CAD and T2DM might have a triglyceride level that would allow them to receive icosapent ethyl. One population-based study in Canada of nearly 200,000 people with atherosclerotic cardiovascular disease found a 25% prevalence of the triglyceride level needed to qualify to receive icosapent ethyl under current labeling, he noted (Eur Heart J. 2020 Jan 1;41[1]:86-94). However, the FDA label does not specify that triglycerides be measured when fasting, and a nonfasting level of about 150 mg/dL will likely appear for patients with fasting levels that fall as low as about 100 mg/dL, Dr. Bhatt said. He hoped that future studies will assess the efficacy of icosapent ethyl in patients with even lower triglyceride levels.

Other sections of the statement also recommend that clinicians: Target long-term dual-antiplatelet therapy to CAD and T2DM patients with additional high-risk markers such as prior MI, younger age, and tobacco use; prescribe a low-dose oral anticoagulant along with an antiplatelet drug such as aspirin for secondary-prevention patients; promote a blood pressure target of less than 140/90 mm Hg for all CAD and T2DM patients and apply a goal of less than 130/80 mm Hg in higher-risk patients such as blacks, Asians, and those with cerebrovascular disease; and reassure patients that “despite a modest increase in blood sugars, the risk-benefit ratio is clearly in favor of administering statins to people with T2DM and CAD.”

Dr. Arnold had no disclosures. Dr. Bhatt has been an adviser to Cardax, Cereno Scientific, Medscape Cardiology, PhaseBio; PLx Pharma, and Regado Biosciences, and he has received research funding from numerous companies including Amarin, the company that markets icosapent ethyl.

 

 

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Radial arteries show CABG survival advantage over saphenous veins

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Tue, 07/21/2020 - 14:33

Coronary bypass surgery patients who received a radial artery as their second bypass conduit had significantly better 10-year survival than did patients who received a saphenous vein graft in a combined analysis of more than 1,000 randomized patients who had originally been enrolled in any of five independent studies.

Dr. Mario F.L. Gaudino

“This is the first report of a survival benefit for CABG [coronary artery bypass grafting] using multiple arterial conduits based on randomized data,” Mario F.L. Gaudino, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

Dr. Gaudino acknowledged several limitations of the finding. First, the analysis included studies that enrolled patients during 1997-2009 in five diverse sites worldwide and, therefore, involved varying surgical methods. Second, the sample size was “relatively low and underpowered, even after 10-year follow-up.” And third, the survival analysis was post hoc, although the statistically significant 27% relative reduction in mortality during follow-up with radial artery bypass, compared with saphenous vein bypass, was fully consistent with both the primary endpoint of the five studies and also with the combined hard endpoint of death and myocardial infarction.

The primary outcome of all-cause death, MI, and repeat revascularization also fell by a relative 27% with radial artery bypass, compared with saphenous vein bypass, and the combined rate of death and MI fell by 23% with radial artery bypass, both statistically significant differences, reported Dr. Gaudino, professor of cardiothoracic surgery at Weill Cornell Medicine, New York.

“The overall message is that radial bypass is associated with better long-term outcomes and potentially better survival,” he concluded.

The left interior thoracic artery (also known as the left internal mammary artery) is well established as the primary CABG conduit, usually used for bypassing the left anterior descending coronary artery, but when a second conduit is needed, several options exist: a saphenous vein, the left radial artery, or possibly the right internal thoracic artery (RITA) as a different arterial option.

Dr. Gaudino claimed that his new results placed the left radial artery clearly superior to the RITA as the second arterial conduit of choice for CABG. Not only does the RITA lack a similar efficacy evidence base from randomized trials, but the method poses a higher risk for surgical wound infections, he noted. The most recent society recommendations on conduit choice for CABG, issued less than 2 years ago by the European Society of Cardiology and European Association for Cardio-Thoracic Surgery, tapped the left radial artery as a level I recommendation over a saphenous vein graft when patients have high-grade coronary stenosis, while the RITA trailed as a level IIa recommendation specified only for patients with a low risk for sternal-wound infection.

Dr. Marc R. Moon

“This was a great study that brings home the point that, in general, the radial artery is better than a saphenous vein graft,” commented Marc R. Moon, MD, a designated discussant and a professor of surgery and chief of cardiac surgery at Washington University, St. Louis.

The long-term follow-up that Dr. Gaudino reported came from extended, patient-level data collection for all 1,036 patients included in the original RADIAL (Radial Artery Database International Alliance) analysis of 5-year outcomes and reported in 2018. Dr. Gaudino and his associates tracked down survival information for all those patients, with outcome records out to at least 10 years for 91% of the original participants and with a mean follow-up that was also 10 years. The prior 2018 report based on 5-year results had also shown a statistically significant reduction in the primary endpoint with radial artery grafting, but at that point, follow-up had not yet collected enough mortality endpoints to produce a statistically significant between-group difference in death from any cause, a shortcoming that may have limited the ability of the prior report to influence U.S. practice.

Dr. Frederick G.P. Welt

“In the United States, there has been very little uptake of multiarterial grafting,” commented Frederick G.P. Welt, MD, a designated discussant, interventional cardiologist, professor of medicine, and associate chief of cardiovascular medicine at the University of Utah, Salt Lake City. The results from several earlier studies did not show much benefit for graft patency using radial arteries, but more recently clinicians have made advances in radial artery harvesting methods, implantation techniques, and adjunctive medications including antispasmodic treatments, Dr. Welt noted. Improved methods for using radial artery grafts and the risk of wound infection with RITA grafts were summarized in an editorial that accompanied the report of the 5-year RADIAL findings.

Dr. Welt said that, among the new findings reported by Dr. Gaudino, “the mortality effect is the most impressive.” Despite the limitations of the post hoc survival analysis, the reduced mortality finding is “nevertheless really important. The patient-level data lend it more credence.”

The study received no commercial funding. Dr. Gaudino had no disclosures. Dr. Moon has been a consultant to Medtronic. Dr. Welt has been an adviser to Medtronic.

SOURCE: Gaudino MFL et al. ACC 20, Abstract 410-11.

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Coronary bypass surgery patients who received a radial artery as their second bypass conduit had significantly better 10-year survival than did patients who received a saphenous vein graft in a combined analysis of more than 1,000 randomized patients who had originally been enrolled in any of five independent studies.

Dr. Mario F.L. Gaudino

“This is the first report of a survival benefit for CABG [coronary artery bypass grafting] using multiple arterial conduits based on randomized data,” Mario F.L. Gaudino, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

Dr. Gaudino acknowledged several limitations of the finding. First, the analysis included studies that enrolled patients during 1997-2009 in five diverse sites worldwide and, therefore, involved varying surgical methods. Second, the sample size was “relatively low and underpowered, even after 10-year follow-up.” And third, the survival analysis was post hoc, although the statistically significant 27% relative reduction in mortality during follow-up with radial artery bypass, compared with saphenous vein bypass, was fully consistent with both the primary endpoint of the five studies and also with the combined hard endpoint of death and myocardial infarction.

The primary outcome of all-cause death, MI, and repeat revascularization also fell by a relative 27% with radial artery bypass, compared with saphenous vein bypass, and the combined rate of death and MI fell by 23% with radial artery bypass, both statistically significant differences, reported Dr. Gaudino, professor of cardiothoracic surgery at Weill Cornell Medicine, New York.

“The overall message is that radial bypass is associated with better long-term outcomes and potentially better survival,” he concluded.

The left interior thoracic artery (also known as the left internal mammary artery) is well established as the primary CABG conduit, usually used for bypassing the left anterior descending coronary artery, but when a second conduit is needed, several options exist: a saphenous vein, the left radial artery, or possibly the right internal thoracic artery (RITA) as a different arterial option.

Dr. Gaudino claimed that his new results placed the left radial artery clearly superior to the RITA as the second arterial conduit of choice for CABG. Not only does the RITA lack a similar efficacy evidence base from randomized trials, but the method poses a higher risk for surgical wound infections, he noted. The most recent society recommendations on conduit choice for CABG, issued less than 2 years ago by the European Society of Cardiology and European Association for Cardio-Thoracic Surgery, tapped the left radial artery as a level I recommendation over a saphenous vein graft when patients have high-grade coronary stenosis, while the RITA trailed as a level IIa recommendation specified only for patients with a low risk for sternal-wound infection.

Dr. Marc R. Moon

“This was a great study that brings home the point that, in general, the radial artery is better than a saphenous vein graft,” commented Marc R. Moon, MD, a designated discussant and a professor of surgery and chief of cardiac surgery at Washington University, St. Louis.

The long-term follow-up that Dr. Gaudino reported came from extended, patient-level data collection for all 1,036 patients included in the original RADIAL (Radial Artery Database International Alliance) analysis of 5-year outcomes and reported in 2018. Dr. Gaudino and his associates tracked down survival information for all those patients, with outcome records out to at least 10 years for 91% of the original participants and with a mean follow-up that was also 10 years. The prior 2018 report based on 5-year results had also shown a statistically significant reduction in the primary endpoint with radial artery grafting, but at that point, follow-up had not yet collected enough mortality endpoints to produce a statistically significant between-group difference in death from any cause, a shortcoming that may have limited the ability of the prior report to influence U.S. practice.

Dr. Frederick G.P. Welt

“In the United States, there has been very little uptake of multiarterial grafting,” commented Frederick G.P. Welt, MD, a designated discussant, interventional cardiologist, professor of medicine, and associate chief of cardiovascular medicine at the University of Utah, Salt Lake City. The results from several earlier studies did not show much benefit for graft patency using radial arteries, but more recently clinicians have made advances in radial artery harvesting methods, implantation techniques, and adjunctive medications including antispasmodic treatments, Dr. Welt noted. Improved methods for using radial artery grafts and the risk of wound infection with RITA grafts were summarized in an editorial that accompanied the report of the 5-year RADIAL findings.

Dr. Welt said that, among the new findings reported by Dr. Gaudino, “the mortality effect is the most impressive.” Despite the limitations of the post hoc survival analysis, the reduced mortality finding is “nevertheless really important. The patient-level data lend it more credence.”

The study received no commercial funding. Dr. Gaudino had no disclosures. Dr. Moon has been a consultant to Medtronic. Dr. Welt has been an adviser to Medtronic.

SOURCE: Gaudino MFL et al. ACC 20, Abstract 410-11.

Coronary bypass surgery patients who received a radial artery as their second bypass conduit had significantly better 10-year survival than did patients who received a saphenous vein graft in a combined analysis of more than 1,000 randomized patients who had originally been enrolled in any of five independent studies.

Dr. Mario F.L. Gaudino

“This is the first report of a survival benefit for CABG [coronary artery bypass grafting] using multiple arterial conduits based on randomized data,” Mario F.L. Gaudino, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

Dr. Gaudino acknowledged several limitations of the finding. First, the analysis included studies that enrolled patients during 1997-2009 in five diverse sites worldwide and, therefore, involved varying surgical methods. Second, the sample size was “relatively low and underpowered, even after 10-year follow-up.” And third, the survival analysis was post hoc, although the statistically significant 27% relative reduction in mortality during follow-up with radial artery bypass, compared with saphenous vein bypass, was fully consistent with both the primary endpoint of the five studies and also with the combined hard endpoint of death and myocardial infarction.

The primary outcome of all-cause death, MI, and repeat revascularization also fell by a relative 27% with radial artery bypass, compared with saphenous vein bypass, and the combined rate of death and MI fell by 23% with radial artery bypass, both statistically significant differences, reported Dr. Gaudino, professor of cardiothoracic surgery at Weill Cornell Medicine, New York.

“The overall message is that radial bypass is associated with better long-term outcomes and potentially better survival,” he concluded.

The left interior thoracic artery (also known as the left internal mammary artery) is well established as the primary CABG conduit, usually used for bypassing the left anterior descending coronary artery, but when a second conduit is needed, several options exist: a saphenous vein, the left radial artery, or possibly the right internal thoracic artery (RITA) as a different arterial option.

Dr. Gaudino claimed that his new results placed the left radial artery clearly superior to the RITA as the second arterial conduit of choice for CABG. Not only does the RITA lack a similar efficacy evidence base from randomized trials, but the method poses a higher risk for surgical wound infections, he noted. The most recent society recommendations on conduit choice for CABG, issued less than 2 years ago by the European Society of Cardiology and European Association for Cardio-Thoracic Surgery, tapped the left radial artery as a level I recommendation over a saphenous vein graft when patients have high-grade coronary stenosis, while the RITA trailed as a level IIa recommendation specified only for patients with a low risk for sternal-wound infection.

Dr. Marc R. Moon

“This was a great study that brings home the point that, in general, the radial artery is better than a saphenous vein graft,” commented Marc R. Moon, MD, a designated discussant and a professor of surgery and chief of cardiac surgery at Washington University, St. Louis.

The long-term follow-up that Dr. Gaudino reported came from extended, patient-level data collection for all 1,036 patients included in the original RADIAL (Radial Artery Database International Alliance) analysis of 5-year outcomes and reported in 2018. Dr. Gaudino and his associates tracked down survival information for all those patients, with outcome records out to at least 10 years for 91% of the original participants and with a mean follow-up that was also 10 years. The prior 2018 report based on 5-year results had also shown a statistically significant reduction in the primary endpoint with radial artery grafting, but at that point, follow-up had not yet collected enough mortality endpoints to produce a statistically significant between-group difference in death from any cause, a shortcoming that may have limited the ability of the prior report to influence U.S. practice.

Dr. Frederick G.P. Welt

“In the United States, there has been very little uptake of multiarterial grafting,” commented Frederick G.P. Welt, MD, a designated discussant, interventional cardiologist, professor of medicine, and associate chief of cardiovascular medicine at the University of Utah, Salt Lake City. The results from several earlier studies did not show much benefit for graft patency using radial arteries, but more recently clinicians have made advances in radial artery harvesting methods, implantation techniques, and adjunctive medications including antispasmodic treatments, Dr. Welt noted. Improved methods for using radial artery grafts and the risk of wound infection with RITA grafts were summarized in an editorial that accompanied the report of the 5-year RADIAL findings.

Dr. Welt said that, among the new findings reported by Dr. Gaudino, “the mortality effect is the most impressive.” Despite the limitations of the post hoc survival analysis, the reduced mortality finding is “nevertheless really important. The patient-level data lend it more credence.”

The study received no commercial funding. Dr. Gaudino had no disclosures. Dr. Moon has been a consultant to Medtronic. Dr. Welt has been an adviser to Medtronic.

SOURCE: Gaudino MFL et al. ACC 20, Abstract 410-11.

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VOYAGER PAD: Clopidogrel adds no benefit to rivaroxaban plus aspirin after PAD interventions

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The VOYAGER PAD results from more than 6,500 patients created the biggest evidence base by far ever collected from patients with symptomatic peripheral artery disease (PAD) who underwent a vascular intervention, and showed that the combination of twice-daily rivaroxaban and once-daily aspirin was safe and more effective than aspirin alone for reducing future thrombotic and ischemic events.

Dr. William R. Hiatt

Following that report on March 28, a prespecified subgroup analysis presented the next day showed that adding clopidogrel to this two-drug combination produced no added efficacy but caused additional bleeding episodes, suggesting that the common practice of using clopidogrel plus aspirin in these patients, especially those who receive a stent in a peripheral artery, should either fall by the wayside or be used very briefly.

“In the absence of clear benefit, clopidogrel exposure along with aspirin and rivaroxaban should be minimized or avoided to reduce this risk,” William R. Hiatt, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic. But he also cautioned that “we did not control for clopidogrel use, and so the patients who received clopidogrel look different [from patients who did not receive clopidogrel]. We must be cautious in interpreting differences between patients on or off clopidogrel,” warned Dr. Hiatt, a lead investigator for VOYAGER PAD, professor for cardiovascular research at the University of Colorado at Denver in Aurora and president of the affiliated Colorado Prevention Center.

In addition to this substantial caveat, the finding that clopidogrel appeared to add no extra benefit to the rivaroxaban/aspirin regimen “contradicts some dogmas that have been in the field for decades,” Dr. Hiatt said. Use of dual-antiplatelet therapy (DAPT), in this setting usually aspirin and clopidogrel, in patients who have just undergone lower-extremity revascularization is “current dogma,” even though it is not based on any direct evidence for efficacy, but instead came on the scene as “an extrapolation from the coronary artery literature, where it does have some benefit, particularly after percutaneous coronary intervention,” he explained.

The only reported study results to examine use of DAPT in patients who underwent peripheral artery revascularization focused entirely on patients who had a surgical procedure and showed no added benefit from DAPT over aspirin only in a multicenter, randomized trial with 851 patients (J Vasc Surg. 2010 Oct;52[4]:825-33), Dr. Hiatt noted. In VOYAGER PAD, two-thirds of all patients underwent an endovascular, not surgical, peripheral intervention, and among those treated with clopidogrel, 91% had endovascular treatment.

“We’re not saying don’t use DAPT, but patients on three drugs are at higher bleeding risk than patients on two drugs. I think our data also suggest starting rivaroxaban immediately after a procedure [as was done in VOYAGER PAD], and not waiting to complete a course of DAPT,” Dr. Hiatt said.

Other experts embraced Dr. Hiatt’s take on these findings, while warning that it may take some time for the message to penetrate into practice.

The overall VOYAGER PAD results “are practice changing for vascular interventions; it was by an order of magnitude the largest vascular intervention trial ever conducted,” commented Sahil A. Parikh, MD, a designated discussant, interventional cardiologist, and director of endovascular services at New York–Presbyterian Medical Center. “The data suggest that the value of clopidogrel is questionable, but the added hazard is not questionable” when given to patients on top of rivaroxaban and aspirin. The results “certainly beg the question of whether one should use DAPT at all, and if so, for how long.”



Use of DAPT in patients undergoing peripheral revascularization, especially patients receiving a stent, has been “dogma,” Dr. Parikh agreed. “It’s been pounded into our heads that DAPT is standard care, so it will take some time to penetrate into the practicing community.”

“Could there be patients who could benefit from triple therapy? That’s possible, but it needs testing,” commented Mark A. Creager, MD, professor of medicine and director of the Heart and Vascular Center at Dartmouth-Hitchcock Medical Center in Lebanon, N.H. “We’ve made terrific strides with the results from VOYAGER PAD,” and from the earlier COMPASS trial, which proved the benefit of rivaroxaban and aspirin in patients with stable atherosclerotic vascular disease including many PAD patients (N Engl J Med. 2017 Oct 5;377[14]:1319-30). Use of rivaroxaban and aspirin in PAD patients based on the COMPASS results “is beginning to make an impact, but has a long way to go,” Dr. Creager said in an interview.

In late 2018, the Food and Drug Administration gave rivaroxaban a revised labeling that included an indication for patients with PAD based on the COMPASS findings. The VOYAGER PAD and COMPASS trials are especially noteworthy because “they opened a whole area [of study] in patients with peripheral vascular disease, ” he added.

The prespecified analysis that Dr. Hiatt reported analyzed outcomes among the 51% of patients enrolled in VOYAGER PAD (Vascular Outcomes Study of Acetylsalicylic Acid Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease) who received clopidogrel during follow-up at the discretion of their treating physician and the outcomes among the remainder who did not. The two subgroups showed several statistically significant differences in the prevalence of various comorbidities and in some baseline demographic and clinical metrics, and the analyses that Dr. Hiatt reported did not attempt to correct for these differences. Patients who received clopidogrel had the drug on board for a median of 29 days, and about 58% received it for 30 days or less.

The main finding of his analysis was that “adding clopidogrel did not modify benefit at all” from the perspective of the primary endpoint of VOYAGER PAD, the incidence of a five-item list of adverse events (acute limb ischemia, major amputation for vascular cause, myocardial infarction, ischemic stroke, and cardiovascular death) during a median follow-up of 28 months (N Engl J Med. 2020 Mar 28. doi: 10.1056/NEJMoa2000052), said Dr. Hiatt. Among patients on clopidogrel, those treated with both rivaroxaban and aspirin had a 16.0% incidence of the primary endpoint, compared with an 18.3% rate among patients on aspirin only, for a 15% relative risk reduction, identical to the study’s primary result. Among patients not on clopidogrel, the primary endpoint occurred in 18.7% of patients on rivaroxaban plus aspirin and in 21.5% of those on aspirin only, a 14% relative risk reduction. The analyses also showed that adding clopidogrel appeared to increase the rate of bleeding episodes, particularly the incidence of major bleeds by the criteria of the International Society on Thrombosis and Haemostasis (ISTH), which rose among patients on aspirin alone from 3.3% without clopidogrel treatment to 4.9% with clopidogrel, and in patients on rivaroxaban plus aspirin these major bleeds increased from 5.4% with no clopidogrel to 6.5% with clopidogrel.

An especially revealing further analysis showed that, among those who also received rivaroxaban and aspirin, clopidogrel treatment for more than 30 days led to substantially more bleeding problems, compared with patients who received the drug for 30 days or less. Patients who received clopidogrel for more than 30 days as part of a triple-drug regimen had a 3.0% rate of major ISTH bleeds during 180 days of follow-up, compared with a 0.9% rate for patients in the aspirin-alone group who also received clopidogrel, a 2.1% between-group difference. In contrast, the difference in major ISTH bleeds between the two treatment arms in the subgroup who received clopidogrel for 30 days or less was 0.7%.

Dr. Gregory Piazza

“What’s inarguable is that the course of clopidogrel should be as short as possible, probably not more than 30 days unless there is a real extenuating rationale,” commented designated discussant Gregory Piazza, MD, a cardiologist at Brigham and Women’s Hospital in Boston.

VOYAGER PAD was sponsored by Bayer and Janssen, the companies that market rivaroxaban (Xarelto). The institution that Dr. Hiatt leads has received research funding from Bayer and Janssen and from Amgen. Dr. Parikh has been a consultant to Terumo; has received research funding from Shockwave, Surmodics, and Trireme; has worked on trial monitoring for Boston Scientific and Silk Road; and has had other financial relationships with Abbott, Boston Scientific, and Medtronic. Dr. Creager had no disclosures. Dr. Piazza has received research grants from Bayer and Janssen, as well as Bristol-Myers Squibb, Diiachi, EKOS, and Portola, and he has been a consultant to Optum, Pfizer, and Thrombolex.

SOURCE: Hiatt WR et al. ACC 20, Abstract 406-13.

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The VOYAGER PAD results from more than 6,500 patients created the biggest evidence base by far ever collected from patients with symptomatic peripheral artery disease (PAD) who underwent a vascular intervention, and showed that the combination of twice-daily rivaroxaban and once-daily aspirin was safe and more effective than aspirin alone for reducing future thrombotic and ischemic events.

Dr. William R. Hiatt

Following that report on March 28, a prespecified subgroup analysis presented the next day showed that adding clopidogrel to this two-drug combination produced no added efficacy but caused additional bleeding episodes, suggesting that the common practice of using clopidogrel plus aspirin in these patients, especially those who receive a stent in a peripheral artery, should either fall by the wayside or be used very briefly.

“In the absence of clear benefit, clopidogrel exposure along with aspirin and rivaroxaban should be minimized or avoided to reduce this risk,” William R. Hiatt, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic. But he also cautioned that “we did not control for clopidogrel use, and so the patients who received clopidogrel look different [from patients who did not receive clopidogrel]. We must be cautious in interpreting differences between patients on or off clopidogrel,” warned Dr. Hiatt, a lead investigator for VOYAGER PAD, professor for cardiovascular research at the University of Colorado at Denver in Aurora and president of the affiliated Colorado Prevention Center.

In addition to this substantial caveat, the finding that clopidogrel appeared to add no extra benefit to the rivaroxaban/aspirin regimen “contradicts some dogmas that have been in the field for decades,” Dr. Hiatt said. Use of dual-antiplatelet therapy (DAPT), in this setting usually aspirin and clopidogrel, in patients who have just undergone lower-extremity revascularization is “current dogma,” even though it is not based on any direct evidence for efficacy, but instead came on the scene as “an extrapolation from the coronary artery literature, where it does have some benefit, particularly after percutaneous coronary intervention,” he explained.

The only reported study results to examine use of DAPT in patients who underwent peripheral artery revascularization focused entirely on patients who had a surgical procedure and showed no added benefit from DAPT over aspirin only in a multicenter, randomized trial with 851 patients (J Vasc Surg. 2010 Oct;52[4]:825-33), Dr. Hiatt noted. In VOYAGER PAD, two-thirds of all patients underwent an endovascular, not surgical, peripheral intervention, and among those treated with clopidogrel, 91% had endovascular treatment.

“We’re not saying don’t use DAPT, but patients on three drugs are at higher bleeding risk than patients on two drugs. I think our data also suggest starting rivaroxaban immediately after a procedure [as was done in VOYAGER PAD], and not waiting to complete a course of DAPT,” Dr. Hiatt said.

Other experts embraced Dr. Hiatt’s take on these findings, while warning that it may take some time for the message to penetrate into practice.

The overall VOYAGER PAD results “are practice changing for vascular interventions; it was by an order of magnitude the largest vascular intervention trial ever conducted,” commented Sahil A. Parikh, MD, a designated discussant, interventional cardiologist, and director of endovascular services at New York–Presbyterian Medical Center. “The data suggest that the value of clopidogrel is questionable, but the added hazard is not questionable” when given to patients on top of rivaroxaban and aspirin. The results “certainly beg the question of whether one should use DAPT at all, and if so, for how long.”



Use of DAPT in patients undergoing peripheral revascularization, especially patients receiving a stent, has been “dogma,” Dr. Parikh agreed. “It’s been pounded into our heads that DAPT is standard care, so it will take some time to penetrate into the practicing community.”

“Could there be patients who could benefit from triple therapy? That’s possible, but it needs testing,” commented Mark A. Creager, MD, professor of medicine and director of the Heart and Vascular Center at Dartmouth-Hitchcock Medical Center in Lebanon, N.H. “We’ve made terrific strides with the results from VOYAGER PAD,” and from the earlier COMPASS trial, which proved the benefit of rivaroxaban and aspirin in patients with stable atherosclerotic vascular disease including many PAD patients (N Engl J Med. 2017 Oct 5;377[14]:1319-30). Use of rivaroxaban and aspirin in PAD patients based on the COMPASS results “is beginning to make an impact, but has a long way to go,” Dr. Creager said in an interview.

In late 2018, the Food and Drug Administration gave rivaroxaban a revised labeling that included an indication for patients with PAD based on the COMPASS findings. The VOYAGER PAD and COMPASS trials are especially noteworthy because “they opened a whole area [of study] in patients with peripheral vascular disease, ” he added.

The prespecified analysis that Dr. Hiatt reported analyzed outcomes among the 51% of patients enrolled in VOYAGER PAD (Vascular Outcomes Study of Acetylsalicylic Acid Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease) who received clopidogrel during follow-up at the discretion of their treating physician and the outcomes among the remainder who did not. The two subgroups showed several statistically significant differences in the prevalence of various comorbidities and in some baseline demographic and clinical metrics, and the analyses that Dr. Hiatt reported did not attempt to correct for these differences. Patients who received clopidogrel had the drug on board for a median of 29 days, and about 58% received it for 30 days or less.

The main finding of his analysis was that “adding clopidogrel did not modify benefit at all” from the perspective of the primary endpoint of VOYAGER PAD, the incidence of a five-item list of adverse events (acute limb ischemia, major amputation for vascular cause, myocardial infarction, ischemic stroke, and cardiovascular death) during a median follow-up of 28 months (N Engl J Med. 2020 Mar 28. doi: 10.1056/NEJMoa2000052), said Dr. Hiatt. Among patients on clopidogrel, those treated with both rivaroxaban and aspirin had a 16.0% incidence of the primary endpoint, compared with an 18.3% rate among patients on aspirin only, for a 15% relative risk reduction, identical to the study’s primary result. Among patients not on clopidogrel, the primary endpoint occurred in 18.7% of patients on rivaroxaban plus aspirin and in 21.5% of those on aspirin only, a 14% relative risk reduction. The analyses also showed that adding clopidogrel appeared to increase the rate of bleeding episodes, particularly the incidence of major bleeds by the criteria of the International Society on Thrombosis and Haemostasis (ISTH), which rose among patients on aspirin alone from 3.3% without clopidogrel treatment to 4.9% with clopidogrel, and in patients on rivaroxaban plus aspirin these major bleeds increased from 5.4% with no clopidogrel to 6.5% with clopidogrel.

An especially revealing further analysis showed that, among those who also received rivaroxaban and aspirin, clopidogrel treatment for more than 30 days led to substantially more bleeding problems, compared with patients who received the drug for 30 days or less. Patients who received clopidogrel for more than 30 days as part of a triple-drug regimen had a 3.0% rate of major ISTH bleeds during 180 days of follow-up, compared with a 0.9% rate for patients in the aspirin-alone group who also received clopidogrel, a 2.1% between-group difference. In contrast, the difference in major ISTH bleeds between the two treatment arms in the subgroup who received clopidogrel for 30 days or less was 0.7%.

Dr. Gregory Piazza

“What’s inarguable is that the course of clopidogrel should be as short as possible, probably not more than 30 days unless there is a real extenuating rationale,” commented designated discussant Gregory Piazza, MD, a cardiologist at Brigham and Women’s Hospital in Boston.

VOYAGER PAD was sponsored by Bayer and Janssen, the companies that market rivaroxaban (Xarelto). The institution that Dr. Hiatt leads has received research funding from Bayer and Janssen and from Amgen. Dr. Parikh has been a consultant to Terumo; has received research funding from Shockwave, Surmodics, and Trireme; has worked on trial monitoring for Boston Scientific and Silk Road; and has had other financial relationships with Abbott, Boston Scientific, and Medtronic. Dr. Creager had no disclosures. Dr. Piazza has received research grants from Bayer and Janssen, as well as Bristol-Myers Squibb, Diiachi, EKOS, and Portola, and he has been a consultant to Optum, Pfizer, and Thrombolex.

SOURCE: Hiatt WR et al. ACC 20, Abstract 406-13.

The VOYAGER PAD results from more than 6,500 patients created the biggest evidence base by far ever collected from patients with symptomatic peripheral artery disease (PAD) who underwent a vascular intervention, and showed that the combination of twice-daily rivaroxaban and once-daily aspirin was safe and more effective than aspirin alone for reducing future thrombotic and ischemic events.

Dr. William R. Hiatt

Following that report on March 28, a prespecified subgroup analysis presented the next day showed that adding clopidogrel to this two-drug combination produced no added efficacy but caused additional bleeding episodes, suggesting that the common practice of using clopidogrel plus aspirin in these patients, especially those who receive a stent in a peripheral artery, should either fall by the wayside or be used very briefly.

“In the absence of clear benefit, clopidogrel exposure along with aspirin and rivaroxaban should be minimized or avoided to reduce this risk,” William R. Hiatt, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic. But he also cautioned that “we did not control for clopidogrel use, and so the patients who received clopidogrel look different [from patients who did not receive clopidogrel]. We must be cautious in interpreting differences between patients on or off clopidogrel,” warned Dr. Hiatt, a lead investigator for VOYAGER PAD, professor for cardiovascular research at the University of Colorado at Denver in Aurora and president of the affiliated Colorado Prevention Center.

In addition to this substantial caveat, the finding that clopidogrel appeared to add no extra benefit to the rivaroxaban/aspirin regimen “contradicts some dogmas that have been in the field for decades,” Dr. Hiatt said. Use of dual-antiplatelet therapy (DAPT), in this setting usually aspirin and clopidogrel, in patients who have just undergone lower-extremity revascularization is “current dogma,” even though it is not based on any direct evidence for efficacy, but instead came on the scene as “an extrapolation from the coronary artery literature, where it does have some benefit, particularly after percutaneous coronary intervention,” he explained.

The only reported study results to examine use of DAPT in patients who underwent peripheral artery revascularization focused entirely on patients who had a surgical procedure and showed no added benefit from DAPT over aspirin only in a multicenter, randomized trial with 851 patients (J Vasc Surg. 2010 Oct;52[4]:825-33), Dr. Hiatt noted. In VOYAGER PAD, two-thirds of all patients underwent an endovascular, not surgical, peripheral intervention, and among those treated with clopidogrel, 91% had endovascular treatment.

“We’re not saying don’t use DAPT, but patients on three drugs are at higher bleeding risk than patients on two drugs. I think our data also suggest starting rivaroxaban immediately after a procedure [as was done in VOYAGER PAD], and not waiting to complete a course of DAPT,” Dr. Hiatt said.

Other experts embraced Dr. Hiatt’s take on these findings, while warning that it may take some time for the message to penetrate into practice.

The overall VOYAGER PAD results “are practice changing for vascular interventions; it was by an order of magnitude the largest vascular intervention trial ever conducted,” commented Sahil A. Parikh, MD, a designated discussant, interventional cardiologist, and director of endovascular services at New York–Presbyterian Medical Center. “The data suggest that the value of clopidogrel is questionable, but the added hazard is not questionable” when given to patients on top of rivaroxaban and aspirin. The results “certainly beg the question of whether one should use DAPT at all, and if so, for how long.”



Use of DAPT in patients undergoing peripheral revascularization, especially patients receiving a stent, has been “dogma,” Dr. Parikh agreed. “It’s been pounded into our heads that DAPT is standard care, so it will take some time to penetrate into the practicing community.”

“Could there be patients who could benefit from triple therapy? That’s possible, but it needs testing,” commented Mark A. Creager, MD, professor of medicine and director of the Heart and Vascular Center at Dartmouth-Hitchcock Medical Center in Lebanon, N.H. “We’ve made terrific strides with the results from VOYAGER PAD,” and from the earlier COMPASS trial, which proved the benefit of rivaroxaban and aspirin in patients with stable atherosclerotic vascular disease including many PAD patients (N Engl J Med. 2017 Oct 5;377[14]:1319-30). Use of rivaroxaban and aspirin in PAD patients based on the COMPASS results “is beginning to make an impact, but has a long way to go,” Dr. Creager said in an interview.

In late 2018, the Food and Drug Administration gave rivaroxaban a revised labeling that included an indication for patients with PAD based on the COMPASS findings. The VOYAGER PAD and COMPASS trials are especially noteworthy because “they opened a whole area [of study] in patients with peripheral vascular disease, ” he added.

The prespecified analysis that Dr. Hiatt reported analyzed outcomes among the 51% of patients enrolled in VOYAGER PAD (Vascular Outcomes Study of Acetylsalicylic Acid Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease) who received clopidogrel during follow-up at the discretion of their treating physician and the outcomes among the remainder who did not. The two subgroups showed several statistically significant differences in the prevalence of various comorbidities and in some baseline demographic and clinical metrics, and the analyses that Dr. Hiatt reported did not attempt to correct for these differences. Patients who received clopidogrel had the drug on board for a median of 29 days, and about 58% received it for 30 days or less.

The main finding of his analysis was that “adding clopidogrel did not modify benefit at all” from the perspective of the primary endpoint of VOYAGER PAD, the incidence of a five-item list of adverse events (acute limb ischemia, major amputation for vascular cause, myocardial infarction, ischemic stroke, and cardiovascular death) during a median follow-up of 28 months (N Engl J Med. 2020 Mar 28. doi: 10.1056/NEJMoa2000052), said Dr. Hiatt. Among patients on clopidogrel, those treated with both rivaroxaban and aspirin had a 16.0% incidence of the primary endpoint, compared with an 18.3% rate among patients on aspirin only, for a 15% relative risk reduction, identical to the study’s primary result. Among patients not on clopidogrel, the primary endpoint occurred in 18.7% of patients on rivaroxaban plus aspirin and in 21.5% of those on aspirin only, a 14% relative risk reduction. The analyses also showed that adding clopidogrel appeared to increase the rate of bleeding episodes, particularly the incidence of major bleeds by the criteria of the International Society on Thrombosis and Haemostasis (ISTH), which rose among patients on aspirin alone from 3.3% without clopidogrel treatment to 4.9% with clopidogrel, and in patients on rivaroxaban plus aspirin these major bleeds increased from 5.4% with no clopidogrel to 6.5% with clopidogrel.

An especially revealing further analysis showed that, among those who also received rivaroxaban and aspirin, clopidogrel treatment for more than 30 days led to substantially more bleeding problems, compared with patients who received the drug for 30 days or less. Patients who received clopidogrel for more than 30 days as part of a triple-drug regimen had a 3.0% rate of major ISTH bleeds during 180 days of follow-up, compared with a 0.9% rate for patients in the aspirin-alone group who also received clopidogrel, a 2.1% between-group difference. In contrast, the difference in major ISTH bleeds between the two treatment arms in the subgroup who received clopidogrel for 30 days or less was 0.7%.

Dr. Gregory Piazza

“What’s inarguable is that the course of clopidogrel should be as short as possible, probably not more than 30 days unless there is a real extenuating rationale,” commented designated discussant Gregory Piazza, MD, a cardiologist at Brigham and Women’s Hospital in Boston.

VOYAGER PAD was sponsored by Bayer and Janssen, the companies that market rivaroxaban (Xarelto). The institution that Dr. Hiatt leads has received research funding from Bayer and Janssen and from Amgen. Dr. Parikh has been a consultant to Terumo; has received research funding from Shockwave, Surmodics, and Trireme; has worked on trial monitoring for Boston Scientific and Silk Road; and has had other financial relationships with Abbott, Boston Scientific, and Medtronic. Dr. Creager had no disclosures. Dr. Piazza has received research grants from Bayer and Janssen, as well as Bristol-Myers Squibb, Diiachi, EKOS, and Portola, and he has been a consultant to Optum, Pfizer, and Thrombolex.

SOURCE: Hiatt WR et al. ACC 20, Abstract 406-13.

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New lipid-lowering drug class slashes LDL in HoFH patients

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Tue, 07/21/2020 - 14:33

Evinacumab, the first agent from a new class of lipid-lowering drugs, showed a “remarkable” and unprecedented level of LDL-cholesterol lowering in a pivotal trial with 65 patients with homozygous familial hypercholesterolemia.

Dr. Frederick Raal

Monthly intravenous infusions of evinacumab cut LDL cholesterol levels by an average of 135 mg/dL from baseline, a 47% mean reduction, after 24 weeks of treatment in 43 homozygous familial hypercholesterolemia (HoFH) patients, Frederick Raal, MBChB, said on March 30 in a video presentation of his research at the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.

Evinacumab is a human monoclonal antibody inhibitor of angiopoietin-like 3, a liver protein that boosts levels of LDL cholesterol and triglycerides (TG).

Another notable effect of the novel agent was that it was equally effective in the roughly one-third of patients with a minimal residual level of LDL receptor activity, patients know as having “null/null” mutations. “For the first time, we see HoFH patients getting to [lipid] targets that we never thought would be possible,” said Dr. Raal, professor and head of endocrinology and metabolism at the University of Witwatersrand in Johannesburg, South Africa. “This works in patients without residual LDL receptor function.” The drug was also generally very well tolerated, he said, causing no treatment-related serious adverse events during the brief treatment period of 24 weeks.

“One of the major, remarkable findings in this study was the effect on null/null patients,” which contrasts with the effects of other, more established drugs for treating dyslipidemia like statins and PCSK9 inhibitors, which work by increasing the number of LDL receptors on cells. The demonstrated efficacy and safety of evinacumab in null/null patients “is a definite advance,” commented Anne C. Goldberg, MD, a lipidologist and professor of medicine at Washington University in St. Louis.

The placebo-controlled trial randomized patients at 30 sites in 11 countries who were at least 12 years old and had documented mutations in both of their LDL receptor genes and a serum level of LDL cholesterol that was at least 500 mg/dL on no treatment. Patients averaged about 40 years of age; about 30% had null/null mutations, more than 90% were on statin treatment, and about three-quarters were receiving regular treatment with a PCSK9 inhibitor. At baseline, LDL cholesterol levels averaged about 250 mg/dL.

The study’s primary endpoint was the between-group percentage change in LDL cholesterol level after 24 weeks, which fell by 47% from baseline with evinacumab treatment and increased by an average of 2% among 22 patients who received placebo injections; so evinacumab cut this measure by 49%, compared with placebo after 24 weeks, a statistically significant difference. A cut of baseline LDL cholesterol by at least 50% occurred in 56% of the evinacumab-treated patients and in 5% of controls.

In addition to its LDL reduction, another notable effect of evinacumab was that it trimmed baseline triglyceride levels by half, consistent with prior reports of the drug’s effect on this measure, although average triglyceride levels in the enrolled patients fell within the normal range prior to treatment.

Evinacumab “will probably be very effective in treating patients with hypertriglyceridemia; those studies are ongoing,” noted Dr. Raal. But, he added, “this drug will probably be reserved for severe” dyslipidemia cases, not for “the garden variety of moderate hypertriglyceridemia or hypercholesterolemia.”

Dr. Dirk Blom

Evinacumab “may be a fairly broad-spectrum lipid-lowering drug, but it should be reserved for severe cases,” agreed Dirk Blom, MBChB, head of lipidology at the University of Capetown, South Africa. “This will likely remain a fairly expensive drug, and we wouldn’t want to use it across the board, but for difficult to treat patients with either severe hypercholesterolemia or hypertriglyceridemia, I think this will have very significant advantages,” he commented.

“Drugs that reduce triglycerides by large amounts may prove to have cardiovascular disease benefits, but that remains to be proven in large, long-term outcome trials,” commented Deepak Bhatt, MD, professor of medicine at Harvard Medical School and executive director of interventional cardiology programs at Brigham and Women’s Hospital, both in Boston. “But for right now, for most patients with more common forms of elevated LDL cholesterol, the treatment options include statins, ezetimibe [Zetia], and PCSK9 inhibitors, and for more common levels of elevated triglycerides, it’s icosapent ethyl [Vascepa],” Dr. Bhatt said.

Dr. Deepak L. Bhatt

The study was sponsored by Regeneron, the company developing evinacumab and which is partially owned by Sanofi. Dr. Raal has received personal fees and/or research funding from Regeneron, Sanofi Aventis, Amgen, and The Medicines Company. Dr. Goldberg has received research funding and/or consulting fees from Regeneron and Sanofi, Akcea, Amarin, Amgen, Esperion, Ionis, Merck, Novartis, and Pfizer. Dr. Blom has been a consultant to and/or received research funding from Regeneron, Sanofi, Aegerium, Akcea, Amgen, Amryt, AstraZeneca, Eli Lilly, Esperion, Gemphire, MSD, and Novo Nordisk. Dr. Bhatt has received research funding from many companies including Regeneron and Sanofi.

SOURCE: Raal F. ACC 20. Abstract 411-12.

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Evinacumab, the first agent from a new class of lipid-lowering drugs, showed a “remarkable” and unprecedented level of LDL-cholesterol lowering in a pivotal trial with 65 patients with homozygous familial hypercholesterolemia.

Dr. Frederick Raal

Monthly intravenous infusions of evinacumab cut LDL cholesterol levels by an average of 135 mg/dL from baseline, a 47% mean reduction, after 24 weeks of treatment in 43 homozygous familial hypercholesterolemia (HoFH) patients, Frederick Raal, MBChB, said on March 30 in a video presentation of his research at the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.

Evinacumab is a human monoclonal antibody inhibitor of angiopoietin-like 3, a liver protein that boosts levels of LDL cholesterol and triglycerides (TG).

Another notable effect of the novel agent was that it was equally effective in the roughly one-third of patients with a minimal residual level of LDL receptor activity, patients know as having “null/null” mutations. “For the first time, we see HoFH patients getting to [lipid] targets that we never thought would be possible,” said Dr. Raal, professor and head of endocrinology and metabolism at the University of Witwatersrand in Johannesburg, South Africa. “This works in patients without residual LDL receptor function.” The drug was also generally very well tolerated, he said, causing no treatment-related serious adverse events during the brief treatment period of 24 weeks.

“One of the major, remarkable findings in this study was the effect on null/null patients,” which contrasts with the effects of other, more established drugs for treating dyslipidemia like statins and PCSK9 inhibitors, which work by increasing the number of LDL receptors on cells. The demonstrated efficacy and safety of evinacumab in null/null patients “is a definite advance,” commented Anne C. Goldberg, MD, a lipidologist and professor of medicine at Washington University in St. Louis.

The placebo-controlled trial randomized patients at 30 sites in 11 countries who were at least 12 years old and had documented mutations in both of their LDL receptor genes and a serum level of LDL cholesterol that was at least 500 mg/dL on no treatment. Patients averaged about 40 years of age; about 30% had null/null mutations, more than 90% were on statin treatment, and about three-quarters were receiving regular treatment with a PCSK9 inhibitor. At baseline, LDL cholesterol levels averaged about 250 mg/dL.

The study’s primary endpoint was the between-group percentage change in LDL cholesterol level after 24 weeks, which fell by 47% from baseline with evinacumab treatment and increased by an average of 2% among 22 patients who received placebo injections; so evinacumab cut this measure by 49%, compared with placebo after 24 weeks, a statistically significant difference. A cut of baseline LDL cholesterol by at least 50% occurred in 56% of the evinacumab-treated patients and in 5% of controls.

In addition to its LDL reduction, another notable effect of evinacumab was that it trimmed baseline triglyceride levels by half, consistent with prior reports of the drug’s effect on this measure, although average triglyceride levels in the enrolled patients fell within the normal range prior to treatment.

Evinacumab “will probably be very effective in treating patients with hypertriglyceridemia; those studies are ongoing,” noted Dr. Raal. But, he added, “this drug will probably be reserved for severe” dyslipidemia cases, not for “the garden variety of moderate hypertriglyceridemia or hypercholesterolemia.”

Dr. Dirk Blom

Evinacumab “may be a fairly broad-spectrum lipid-lowering drug, but it should be reserved for severe cases,” agreed Dirk Blom, MBChB, head of lipidology at the University of Capetown, South Africa. “This will likely remain a fairly expensive drug, and we wouldn’t want to use it across the board, but for difficult to treat patients with either severe hypercholesterolemia or hypertriglyceridemia, I think this will have very significant advantages,” he commented.

“Drugs that reduce triglycerides by large amounts may prove to have cardiovascular disease benefits, but that remains to be proven in large, long-term outcome trials,” commented Deepak Bhatt, MD, professor of medicine at Harvard Medical School and executive director of interventional cardiology programs at Brigham and Women’s Hospital, both in Boston. “But for right now, for most patients with more common forms of elevated LDL cholesterol, the treatment options include statins, ezetimibe [Zetia], and PCSK9 inhibitors, and for more common levels of elevated triglycerides, it’s icosapent ethyl [Vascepa],” Dr. Bhatt said.

Dr. Deepak L. Bhatt

The study was sponsored by Regeneron, the company developing evinacumab and which is partially owned by Sanofi. Dr. Raal has received personal fees and/or research funding from Regeneron, Sanofi Aventis, Amgen, and The Medicines Company. Dr. Goldberg has received research funding and/or consulting fees from Regeneron and Sanofi, Akcea, Amarin, Amgen, Esperion, Ionis, Merck, Novartis, and Pfizer. Dr. Blom has been a consultant to and/or received research funding from Regeneron, Sanofi, Aegerium, Akcea, Amgen, Amryt, AstraZeneca, Eli Lilly, Esperion, Gemphire, MSD, and Novo Nordisk. Dr. Bhatt has received research funding from many companies including Regeneron and Sanofi.

SOURCE: Raal F. ACC 20. Abstract 411-12.

Evinacumab, the first agent from a new class of lipid-lowering drugs, showed a “remarkable” and unprecedented level of LDL-cholesterol lowering in a pivotal trial with 65 patients with homozygous familial hypercholesterolemia.

Dr. Frederick Raal

Monthly intravenous infusions of evinacumab cut LDL cholesterol levels by an average of 135 mg/dL from baseline, a 47% mean reduction, after 24 weeks of treatment in 43 homozygous familial hypercholesterolemia (HoFH) patients, Frederick Raal, MBChB, said on March 30 in a video presentation of his research at the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.

Evinacumab is a human monoclonal antibody inhibitor of angiopoietin-like 3, a liver protein that boosts levels of LDL cholesterol and triglycerides (TG).

Another notable effect of the novel agent was that it was equally effective in the roughly one-third of patients with a minimal residual level of LDL receptor activity, patients know as having “null/null” mutations. “For the first time, we see HoFH patients getting to [lipid] targets that we never thought would be possible,” said Dr. Raal, professor and head of endocrinology and metabolism at the University of Witwatersrand in Johannesburg, South Africa. “This works in patients without residual LDL receptor function.” The drug was also generally very well tolerated, he said, causing no treatment-related serious adverse events during the brief treatment period of 24 weeks.

“One of the major, remarkable findings in this study was the effect on null/null patients,” which contrasts with the effects of other, more established drugs for treating dyslipidemia like statins and PCSK9 inhibitors, which work by increasing the number of LDL receptors on cells. The demonstrated efficacy and safety of evinacumab in null/null patients “is a definite advance,” commented Anne C. Goldberg, MD, a lipidologist and professor of medicine at Washington University in St. Louis.

The placebo-controlled trial randomized patients at 30 sites in 11 countries who were at least 12 years old and had documented mutations in both of their LDL receptor genes and a serum level of LDL cholesterol that was at least 500 mg/dL on no treatment. Patients averaged about 40 years of age; about 30% had null/null mutations, more than 90% were on statin treatment, and about three-quarters were receiving regular treatment with a PCSK9 inhibitor. At baseline, LDL cholesterol levels averaged about 250 mg/dL.

The study’s primary endpoint was the between-group percentage change in LDL cholesterol level after 24 weeks, which fell by 47% from baseline with evinacumab treatment and increased by an average of 2% among 22 patients who received placebo injections; so evinacumab cut this measure by 49%, compared with placebo after 24 weeks, a statistically significant difference. A cut of baseline LDL cholesterol by at least 50% occurred in 56% of the evinacumab-treated patients and in 5% of controls.

In addition to its LDL reduction, another notable effect of evinacumab was that it trimmed baseline triglyceride levels by half, consistent with prior reports of the drug’s effect on this measure, although average triglyceride levels in the enrolled patients fell within the normal range prior to treatment.

Evinacumab “will probably be very effective in treating patients with hypertriglyceridemia; those studies are ongoing,” noted Dr. Raal. But, he added, “this drug will probably be reserved for severe” dyslipidemia cases, not for “the garden variety of moderate hypertriglyceridemia or hypercholesterolemia.”

Dr. Dirk Blom

Evinacumab “may be a fairly broad-spectrum lipid-lowering drug, but it should be reserved for severe cases,” agreed Dirk Blom, MBChB, head of lipidology at the University of Capetown, South Africa. “This will likely remain a fairly expensive drug, and we wouldn’t want to use it across the board, but for difficult to treat patients with either severe hypercholesterolemia or hypertriglyceridemia, I think this will have very significant advantages,” he commented.

“Drugs that reduce triglycerides by large amounts may prove to have cardiovascular disease benefits, but that remains to be proven in large, long-term outcome trials,” commented Deepak Bhatt, MD, professor of medicine at Harvard Medical School and executive director of interventional cardiology programs at Brigham and Women’s Hospital, both in Boston. “But for right now, for most patients with more common forms of elevated LDL cholesterol, the treatment options include statins, ezetimibe [Zetia], and PCSK9 inhibitors, and for more common levels of elevated triglycerides, it’s icosapent ethyl [Vascepa],” Dr. Bhatt said.

Dr. Deepak L. Bhatt

The study was sponsored by Regeneron, the company developing evinacumab and which is partially owned by Sanofi. Dr. Raal has received personal fees and/or research funding from Regeneron, Sanofi Aventis, Amgen, and The Medicines Company. Dr. Goldberg has received research funding and/or consulting fees from Regeneron and Sanofi, Akcea, Amarin, Amgen, Esperion, Ionis, Merck, Novartis, and Pfizer. Dr. Blom has been a consultant to and/or received research funding from Regeneron, Sanofi, Aegerium, Akcea, Amgen, Amryt, AstraZeneca, Eli Lilly, Esperion, Gemphire, MSD, and Novo Nordisk. Dr. Bhatt has received research funding from many companies including Regeneron and Sanofi.

SOURCE: Raal F. ACC 20. Abstract 411-12.

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Outcomes-based measurement of TAVR program quality goes live

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Tue, 07/21/2020 - 14:33

 

The long-sought goal of measuring the quality of U.S. transcatheter aortic valve replacement (TAVR) programs by patient outcomes rather than by the surrogate measure of case volume is about to be realized.

Dr. Nimesh D. Desai

Starting more or less immediately, the U.S. national register for all TAVR cases that’s mandated by Food and Drug Administration labeling of these devices and run through a collaboration of the American College of Cardiology and the Society of Thoracic Surgeons will start applying a newly developed and validated five-item metric for measuring 30-day patient outcomes and designed to gauge the quality of TAVR programs.

At first, the only recipients of the data will be the programs themselves, but starting in about a year, by sometime in 2021, the STS/ACC TVT (transcatheter valve therapy) Registry will start to make its star-based rating of TAVR programs available to the public, Nimesh D. Desai, MD, said on March 29 at the joint scientific sessions of the ACC and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic. These societies already make star-based ratings of U.S. programs available to the public for several other types of cardiac interventions, including coronary artery bypass surgery and MI management.



The new, composite metric based on 30-day outcome data “is appropriate for high-stakes applications such as public reporting,” said Dr. Desai, a thoracic surgeon and director of thoracic aortic surgery research at the University of Pennsylvania in Philadelphia. “We’re confident this model can be used for public reporting. It’s undergone extensive testing of its validity.” The steering committee of the STS/ACC TVT Registry commissioned development of the metric, and it’s now “considered approved,” and ready for use, he explained.

To create the new metric, Dr. Desai and his associates used data from 52,561 patients who underwent transfemoral TAVR during 2015-2017 at any of 301 U.S. sites. These data came from a total pool of more than 114,000 patients at 556 sites, but data from many sites weren’t usable because they were not adequately complete. The researchers then identified the top four measures taken during the 30 days following intervention (hospitalization included) that best correlated with 1-year survival and patients’ quality-of-life scores on the Kansas City Cardiomyopathy Questionnaire: stroke; major, life-threatening, or disabling bleed; acute kidney injury (stage III); and moderate or severe paravalvular leak. These outcomes “matter most to patients,” Dr. Desai said.

They used these four outcomes plus 30-day mortality to calculate the programs’ ratings. Among the 52,561 patients, 14% had at least one of these adverse outcomes. The researchers then used a logistic regression model that adjusted for 46 measured variables to calculate how each program performed relative to the average performance of all the programs. Programs with outcomes that fell within the 95% confidence intervals of average performance were rated as performing as expected; those outside rated as performing either better or worse than expected. The results showed 34 centers (11%) had worse than expected outcomes and 25 (8%) had better than expected outcomes, Dr. Desai said.

Dr. Michael Mack

“This is a major step forward in measuring TAVR quality,” commented Michael Mack, MD, a cardiac surgeon with Baylor Scott & White Health in Dallas who has been very active in studying TAVR. “Until now, we used volume as a surrogate for quality, but the precision was not great. This is an extremely welcome metric.” The next step is to eventually use 1-year follow-up data instead of 30-day outcomes, he added.

“With the rapid expansion of TAVR over the past 6-8 years, we’re now at the point to start to do this. It’s an ethical obligation This will be one of the most high-fidelity, valid models for public reporting” of clinical outcomes,” said Joseph Cleveland, MD, a professor of surgery at the University of Colorado at Denver in Aurora. “It’s reassuring that about 90% of the program performed as expected or better than expected,” he added.

 

 


“Transparency and outcomes should drive how TAVR is delivered,” commented Ashish Pershad, MD, an interventional cardiologist at Banner-University Medicine Heart Institute in Phoenix who estimated that he performs about 150 TAVR procedures annually. “This is a step forward. I’ve been waiting for this for a long time. Until now, volume has been used as a surrogate outcome, but we know it’s not accurate. I’m confident that this model is a good starting point.” But Dr. Pershad also had concern that this new approach “can lend itself to some degree of gaming,” like a bleeding event getting classified as minor when it was really major, or outlier patients getting dropped from reports.

Dr. Ashish Pershad

The temptation to cut corners may be higher for TAVR than it’s been for the cardiac-disease metrics that already get publicly reported, like bypass surgery and myocardial infarction management, because of TAVR’s higher cost and higher profile, Dr. Pershad said. Existing measures “have not been as linked to financial disincentive as TAVR might be” because TAVR reimbursements can run as high as $50,000 per case. “The stakes with TAVR are higher,” he said.

Ultimately, the reliable examination of TAVR outcomes that this new metric allows may lead to a shake-up of TAVR programs, Dr. Pershad predicted. “This is clearly a step toward closing down some programs that [consistently] underperform.”

The STS/ACC TVT Registry receives no commercial funding. Dr. Desai has been a consultant to, speaker on behalf of, and received research funding from Gore, and he has also spoken on behalf of Cook, Medtronic, and Terumo Aortic. Dr. Cleveland, Dr. Mack, and Dr. Pershad had no disclosures.

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The long-sought goal of measuring the quality of U.S. transcatheter aortic valve replacement (TAVR) programs by patient outcomes rather than by the surrogate measure of case volume is about to be realized.

Dr. Nimesh D. Desai

Starting more or less immediately, the U.S. national register for all TAVR cases that’s mandated by Food and Drug Administration labeling of these devices and run through a collaboration of the American College of Cardiology and the Society of Thoracic Surgeons will start applying a newly developed and validated five-item metric for measuring 30-day patient outcomes and designed to gauge the quality of TAVR programs.

At first, the only recipients of the data will be the programs themselves, but starting in about a year, by sometime in 2021, the STS/ACC TVT (transcatheter valve therapy) Registry will start to make its star-based rating of TAVR programs available to the public, Nimesh D. Desai, MD, said on March 29 at the joint scientific sessions of the ACC and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic. These societies already make star-based ratings of U.S. programs available to the public for several other types of cardiac interventions, including coronary artery bypass surgery and MI management.



The new, composite metric based on 30-day outcome data “is appropriate for high-stakes applications such as public reporting,” said Dr. Desai, a thoracic surgeon and director of thoracic aortic surgery research at the University of Pennsylvania in Philadelphia. “We’re confident this model can be used for public reporting. It’s undergone extensive testing of its validity.” The steering committee of the STS/ACC TVT Registry commissioned development of the metric, and it’s now “considered approved,” and ready for use, he explained.

To create the new metric, Dr. Desai and his associates used data from 52,561 patients who underwent transfemoral TAVR during 2015-2017 at any of 301 U.S. sites. These data came from a total pool of more than 114,000 patients at 556 sites, but data from many sites weren’t usable because they were not adequately complete. The researchers then identified the top four measures taken during the 30 days following intervention (hospitalization included) that best correlated with 1-year survival and patients’ quality-of-life scores on the Kansas City Cardiomyopathy Questionnaire: stroke; major, life-threatening, or disabling bleed; acute kidney injury (stage III); and moderate or severe paravalvular leak. These outcomes “matter most to patients,” Dr. Desai said.

They used these four outcomes plus 30-day mortality to calculate the programs’ ratings. Among the 52,561 patients, 14% had at least one of these adverse outcomes. The researchers then used a logistic regression model that adjusted for 46 measured variables to calculate how each program performed relative to the average performance of all the programs. Programs with outcomes that fell within the 95% confidence intervals of average performance were rated as performing as expected; those outside rated as performing either better or worse than expected. The results showed 34 centers (11%) had worse than expected outcomes and 25 (8%) had better than expected outcomes, Dr. Desai said.

Dr. Michael Mack

“This is a major step forward in measuring TAVR quality,” commented Michael Mack, MD, a cardiac surgeon with Baylor Scott & White Health in Dallas who has been very active in studying TAVR. “Until now, we used volume as a surrogate for quality, but the precision was not great. This is an extremely welcome metric.” The next step is to eventually use 1-year follow-up data instead of 30-day outcomes, he added.

“With the rapid expansion of TAVR over the past 6-8 years, we’re now at the point to start to do this. It’s an ethical obligation This will be one of the most high-fidelity, valid models for public reporting” of clinical outcomes,” said Joseph Cleveland, MD, a professor of surgery at the University of Colorado at Denver in Aurora. “It’s reassuring that about 90% of the program performed as expected or better than expected,” he added.

 

 


“Transparency and outcomes should drive how TAVR is delivered,” commented Ashish Pershad, MD, an interventional cardiologist at Banner-University Medicine Heart Institute in Phoenix who estimated that he performs about 150 TAVR procedures annually. “This is a step forward. I’ve been waiting for this for a long time. Until now, volume has been used as a surrogate outcome, but we know it’s not accurate. I’m confident that this model is a good starting point.” But Dr. Pershad also had concern that this new approach “can lend itself to some degree of gaming,” like a bleeding event getting classified as minor when it was really major, or outlier patients getting dropped from reports.

Dr. Ashish Pershad

The temptation to cut corners may be higher for TAVR than it’s been for the cardiac-disease metrics that already get publicly reported, like bypass surgery and myocardial infarction management, because of TAVR’s higher cost and higher profile, Dr. Pershad said. Existing measures “have not been as linked to financial disincentive as TAVR might be” because TAVR reimbursements can run as high as $50,000 per case. “The stakes with TAVR are higher,” he said.

Ultimately, the reliable examination of TAVR outcomes that this new metric allows may lead to a shake-up of TAVR programs, Dr. Pershad predicted. “This is clearly a step toward closing down some programs that [consistently] underperform.”

The STS/ACC TVT Registry receives no commercial funding. Dr. Desai has been a consultant to, speaker on behalf of, and received research funding from Gore, and he has also spoken on behalf of Cook, Medtronic, and Terumo Aortic. Dr. Cleveland, Dr. Mack, and Dr. Pershad had no disclosures.

 

The long-sought goal of measuring the quality of U.S. transcatheter aortic valve replacement (TAVR) programs by patient outcomes rather than by the surrogate measure of case volume is about to be realized.

Dr. Nimesh D. Desai

Starting more or less immediately, the U.S. national register for all TAVR cases that’s mandated by Food and Drug Administration labeling of these devices and run through a collaboration of the American College of Cardiology and the Society of Thoracic Surgeons will start applying a newly developed and validated five-item metric for measuring 30-day patient outcomes and designed to gauge the quality of TAVR programs.

At first, the only recipients of the data will be the programs themselves, but starting in about a year, by sometime in 2021, the STS/ACC TVT (transcatheter valve therapy) Registry will start to make its star-based rating of TAVR programs available to the public, Nimesh D. Desai, MD, said on March 29 at the joint scientific sessions of the ACC and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic. These societies already make star-based ratings of U.S. programs available to the public for several other types of cardiac interventions, including coronary artery bypass surgery and MI management.



The new, composite metric based on 30-day outcome data “is appropriate for high-stakes applications such as public reporting,” said Dr. Desai, a thoracic surgeon and director of thoracic aortic surgery research at the University of Pennsylvania in Philadelphia. “We’re confident this model can be used for public reporting. It’s undergone extensive testing of its validity.” The steering committee of the STS/ACC TVT Registry commissioned development of the metric, and it’s now “considered approved,” and ready for use, he explained.

To create the new metric, Dr. Desai and his associates used data from 52,561 patients who underwent transfemoral TAVR during 2015-2017 at any of 301 U.S. sites. These data came from a total pool of more than 114,000 patients at 556 sites, but data from many sites weren’t usable because they were not adequately complete. The researchers then identified the top four measures taken during the 30 days following intervention (hospitalization included) that best correlated with 1-year survival and patients’ quality-of-life scores on the Kansas City Cardiomyopathy Questionnaire: stroke; major, life-threatening, or disabling bleed; acute kidney injury (stage III); and moderate or severe paravalvular leak. These outcomes “matter most to patients,” Dr. Desai said.

They used these four outcomes plus 30-day mortality to calculate the programs’ ratings. Among the 52,561 patients, 14% had at least one of these adverse outcomes. The researchers then used a logistic regression model that adjusted for 46 measured variables to calculate how each program performed relative to the average performance of all the programs. Programs with outcomes that fell within the 95% confidence intervals of average performance were rated as performing as expected; those outside rated as performing either better or worse than expected. The results showed 34 centers (11%) had worse than expected outcomes and 25 (8%) had better than expected outcomes, Dr. Desai said.

Dr. Michael Mack

“This is a major step forward in measuring TAVR quality,” commented Michael Mack, MD, a cardiac surgeon with Baylor Scott & White Health in Dallas who has been very active in studying TAVR. “Until now, we used volume as a surrogate for quality, but the precision was not great. This is an extremely welcome metric.” The next step is to eventually use 1-year follow-up data instead of 30-day outcomes, he added.

“With the rapid expansion of TAVR over the past 6-8 years, we’re now at the point to start to do this. It’s an ethical obligation This will be one of the most high-fidelity, valid models for public reporting” of clinical outcomes,” said Joseph Cleveland, MD, a professor of surgery at the University of Colorado at Denver in Aurora. “It’s reassuring that about 90% of the program performed as expected or better than expected,” he added.

 

 


“Transparency and outcomes should drive how TAVR is delivered,” commented Ashish Pershad, MD, an interventional cardiologist at Banner-University Medicine Heart Institute in Phoenix who estimated that he performs about 150 TAVR procedures annually. “This is a step forward. I’ve been waiting for this for a long time. Until now, volume has been used as a surrogate outcome, but we know it’s not accurate. I’m confident that this model is a good starting point.” But Dr. Pershad also had concern that this new approach “can lend itself to some degree of gaming,” like a bleeding event getting classified as minor when it was really major, or outlier patients getting dropped from reports.

Dr. Ashish Pershad

The temptation to cut corners may be higher for TAVR than it’s been for the cardiac-disease metrics that already get publicly reported, like bypass surgery and myocardial infarction management, because of TAVR’s higher cost and higher profile, Dr. Pershad said. Existing measures “have not been as linked to financial disincentive as TAVR might be” because TAVR reimbursements can run as high as $50,000 per case. “The stakes with TAVR are higher,” he said.

Ultimately, the reliable examination of TAVR outcomes that this new metric allows may lead to a shake-up of TAVR programs, Dr. Pershad predicted. “This is clearly a step toward closing down some programs that [consistently] underperform.”

The STS/ACC TVT Registry receives no commercial funding. Dr. Desai has been a consultant to, speaker on behalf of, and received research funding from Gore, and he has also spoken on behalf of Cook, Medtronic, and Terumo Aortic. Dr. Cleveland, Dr. Mack, and Dr. Pershad had no disclosures.

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Rivaroxaban plus aspirin safely benefits PAD patients after limb revascularization

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A combined antithrombotic regimen of rivaroxaban plus aspirin was safe and effective for reducing ischemic events in patients with symptomatic peripheral artery disease who had just undergone peripheral artery revascularization in VOYAGER PAD, a multicenter randomized trial with nearly 6,600 patients.

Dr. Mark P. Bonaca

The study and its results were a groundbreaking advance for this patient population, who until now have had no evidence-based treatment available, Mark P. Bonaca, MD, said on March 28 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

The study design excluded a small percentage of patients (about 2%) because of their very high bleeding-risk history. Among the treated patients, in those who received a combination of 2.5 mg rivaroxaban twice daily plus 100 mg of aspirin daily, bleeding events were more common, compared with control patients who received aspirin alone. But the patients who received both drugs showed no excess of fatal bleeds or intracranial hemorrhages, and the rate of ischemic events prevented by rivaroxaban plus aspirin exceeded the excess rate of bleeds by three- to sixfold, depending on how bleeding episodes were defined, noted Dr. Bonaca, executive director of CPC Clinical Research and CPC Community Health, an academic research organization affiliated with the University of Colorado at Denver in Aurora.

Dr. Mark A. Creager

“This was a much anticipated and important trial. Those of us who treat patients with lower-limb peripheral artery disease have not had much evidence on how to treat these patients, particularly those who have just undergone revascularization. This trial gives us the evidence,” commented Mark A. Creager, MD, professor of medicine and director of the Heart and Vascular Center at Dartmouth-Hitchcock Medical Center in Lebanon, N.H. “The bleeding risk [from adding rivaroxaban treatment] was substantially less than the benefit from preventing major adverse limb events and major adverse cardiovascular events,” producing a “favorable balance” of benefit, compared with risk, Dr. Creager said in an interview. “In the right patients, the benefit greatly outweighed the risk.”

Dr. Joshua A. Beckman

“This was an incredible trial that will advance care,” commented Joshua A. Beckman, MD, professor of medicine and director of Vascular Medicine at Vanderbilt University in Nashville, Tenn. “The treatment was beneficial for patients across a range of symptom severity, from claudication to critical limb ischemia,” and the results expand the range of patients proven to benefit from the rivaroxaban plus aspirin combination from the types of patients with peripheral artery disease (PAD) enrolled in the COMPASS trial. That pivotal trial showed similar benefit from the dual-antithrombotic regimen, but in patients who had both coronary artery disease as well as atherosclerotic disease in at least one additional vascular bed, such as lower-limb arteries (N Engl J Med. 2017 Oct 5;377[14]:1319-30). In addition to “bringing acute limb ischemia to the cardiovascular community,” the results also identified a very useful time point in the clinical presentation of these patients for starting a combined rivaroxaban plus aspirin regimen: when patients are hospitalized for their revascularization procedure, said Dr. Beckman, a designated discussant for the report.



Among the 6,564 patients randomized in the study, about two-thirds underwent endovascular revascularization within 10 days before starting their study treatment, and the remaining third had undergone surgical revascularization. The study focused on patients “with symptomatic PAD but without known coronary artery disease,” noted Dr. Bonaca.

 

 

VOYAGER PAD trial

The VOYAGER PAD (Vascular Outcomes Study of Acetylsalicylic Acid Along With Rivaroxaban in Endovascular Or Surgical Limb Revascularization for Peripheral Artery Disease) trial enrolled patients during 2015-2018 at 534 sites in 34 countries. The study’s primary endpoint was a composite of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes, and was reduced during a median follow-up of 28 months from 19.9% with aspirin alone to 17.3% on the combined regimen, a 2.6% absolute difference and a 15% relative risk reduction that was statistically significant, an endpoint primarily driven by a reduction in acute limb ischemia. The primary safety endpoint was the rate of TIMI (Thrombolysis in Myocardial Infarction) major bleeds, which was 0.8% higher in the patients who received the anticoagulant, a 43% relative increase that just missed statistical significance. But that result demonstrated the small but important increased risk for bleeding events that the dual regimen produced in these patients, Dr. Bonaca said. Simultaneously with his report the findings also appeared in an article published online (N Engl J Med. 2020 Mar 28. doi: 10.1056/NEJMoa2000052).

Dr. Bonaca cautioned that one limitation of his report on the primary outcome of VOYAGER PAD is that the results of an important subgroup analysis won’t be known until a second report during the ACC online sessions on March 29, which will examine the impact that treatment with the antiplatelet drug clopidogrel had on both the efficacy and safety outcomes. Half of the enrolled patients received clopidogrel at the discretion of their treating physicians; addition or exclusion of concurrent clopidogrel treatment was outside of the study’s design. “Is efficacy the same with or without clopidogrel, and what is the bleeding cost,” especially in patients who receive three antithrombotic drugs? “It will be very important to understand,” Dr. Bonaca said.

Dr. Roxana Mehran

“Until now, we had no idea of what was the best antithrombotic strategy for patients after a successful peripheral vascular intervention.” VOYAGER PAD was “an unprecedented vascular study that addressed an unmet patient need,” commented Roxana Mehran, MD, a designated discussant for the study and professor of medicine and director of Interventional Cardiovascular Research at Mount Sinai Medical Center in New York.

VOYAGER PAD was sponsored by Bayer and Janssen, the companies that market rivaroxaban (Xarelto). The institution that Dr. Bonaca directs has received research funding from Bayer and Janssen, and also from Amgen, Aralez, AstraZeneca, Merck, Novo Nordisk, Pfizer, and Sanofi. Dr. Creager had no disclosures. Dr. Beckman has served as a data safety monitor for Bayer and for Novartis, and has been a consultant to Amgen, AstraZeneca, JanOne and Sanofi. Dr. Mehran has received research funding from Bayer and has been a consultant to Janssen, and she has also received research funding or been a consultant to several other companies.

SOURCE: Bonaca MP et al. ACC 20, Abstract 402-10.

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A combined antithrombotic regimen of rivaroxaban plus aspirin was safe and effective for reducing ischemic events in patients with symptomatic peripheral artery disease who had just undergone peripheral artery revascularization in VOYAGER PAD, a multicenter randomized trial with nearly 6,600 patients.

Dr. Mark P. Bonaca

The study and its results were a groundbreaking advance for this patient population, who until now have had no evidence-based treatment available, Mark P. Bonaca, MD, said on March 28 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

The study design excluded a small percentage of patients (about 2%) because of their very high bleeding-risk history. Among the treated patients, in those who received a combination of 2.5 mg rivaroxaban twice daily plus 100 mg of aspirin daily, bleeding events were more common, compared with control patients who received aspirin alone. But the patients who received both drugs showed no excess of fatal bleeds or intracranial hemorrhages, and the rate of ischemic events prevented by rivaroxaban plus aspirin exceeded the excess rate of bleeds by three- to sixfold, depending on how bleeding episodes were defined, noted Dr. Bonaca, executive director of CPC Clinical Research and CPC Community Health, an academic research organization affiliated with the University of Colorado at Denver in Aurora.

Dr. Mark A. Creager

“This was a much anticipated and important trial. Those of us who treat patients with lower-limb peripheral artery disease have not had much evidence on how to treat these patients, particularly those who have just undergone revascularization. This trial gives us the evidence,” commented Mark A. Creager, MD, professor of medicine and director of the Heart and Vascular Center at Dartmouth-Hitchcock Medical Center in Lebanon, N.H. “The bleeding risk [from adding rivaroxaban treatment] was substantially less than the benefit from preventing major adverse limb events and major adverse cardiovascular events,” producing a “favorable balance” of benefit, compared with risk, Dr. Creager said in an interview. “In the right patients, the benefit greatly outweighed the risk.”

Dr. Joshua A. Beckman

“This was an incredible trial that will advance care,” commented Joshua A. Beckman, MD, professor of medicine and director of Vascular Medicine at Vanderbilt University in Nashville, Tenn. “The treatment was beneficial for patients across a range of symptom severity, from claudication to critical limb ischemia,” and the results expand the range of patients proven to benefit from the rivaroxaban plus aspirin combination from the types of patients with peripheral artery disease (PAD) enrolled in the COMPASS trial. That pivotal trial showed similar benefit from the dual-antithrombotic regimen, but in patients who had both coronary artery disease as well as atherosclerotic disease in at least one additional vascular bed, such as lower-limb arteries (N Engl J Med. 2017 Oct 5;377[14]:1319-30). In addition to “bringing acute limb ischemia to the cardiovascular community,” the results also identified a very useful time point in the clinical presentation of these patients for starting a combined rivaroxaban plus aspirin regimen: when patients are hospitalized for their revascularization procedure, said Dr. Beckman, a designated discussant for the report.



Among the 6,564 patients randomized in the study, about two-thirds underwent endovascular revascularization within 10 days before starting their study treatment, and the remaining third had undergone surgical revascularization. The study focused on patients “with symptomatic PAD but without known coronary artery disease,” noted Dr. Bonaca.

 

 

VOYAGER PAD trial

The VOYAGER PAD (Vascular Outcomes Study of Acetylsalicylic Acid Along With Rivaroxaban in Endovascular Or Surgical Limb Revascularization for Peripheral Artery Disease) trial enrolled patients during 2015-2018 at 534 sites in 34 countries. The study’s primary endpoint was a composite of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes, and was reduced during a median follow-up of 28 months from 19.9% with aspirin alone to 17.3% on the combined regimen, a 2.6% absolute difference and a 15% relative risk reduction that was statistically significant, an endpoint primarily driven by a reduction in acute limb ischemia. The primary safety endpoint was the rate of TIMI (Thrombolysis in Myocardial Infarction) major bleeds, which was 0.8% higher in the patients who received the anticoagulant, a 43% relative increase that just missed statistical significance. But that result demonstrated the small but important increased risk for bleeding events that the dual regimen produced in these patients, Dr. Bonaca said. Simultaneously with his report the findings also appeared in an article published online (N Engl J Med. 2020 Mar 28. doi: 10.1056/NEJMoa2000052).

Dr. Bonaca cautioned that one limitation of his report on the primary outcome of VOYAGER PAD is that the results of an important subgroup analysis won’t be known until a second report during the ACC online sessions on March 29, which will examine the impact that treatment with the antiplatelet drug clopidogrel had on both the efficacy and safety outcomes. Half of the enrolled patients received clopidogrel at the discretion of their treating physicians; addition or exclusion of concurrent clopidogrel treatment was outside of the study’s design. “Is efficacy the same with or without clopidogrel, and what is the bleeding cost,” especially in patients who receive three antithrombotic drugs? “It will be very important to understand,” Dr. Bonaca said.

Dr. Roxana Mehran

“Until now, we had no idea of what was the best antithrombotic strategy for patients after a successful peripheral vascular intervention.” VOYAGER PAD was “an unprecedented vascular study that addressed an unmet patient need,” commented Roxana Mehran, MD, a designated discussant for the study and professor of medicine and director of Interventional Cardiovascular Research at Mount Sinai Medical Center in New York.

VOYAGER PAD was sponsored by Bayer and Janssen, the companies that market rivaroxaban (Xarelto). The institution that Dr. Bonaca directs has received research funding from Bayer and Janssen, and also from Amgen, Aralez, AstraZeneca, Merck, Novo Nordisk, Pfizer, and Sanofi. Dr. Creager had no disclosures. Dr. Beckman has served as a data safety monitor for Bayer and for Novartis, and has been a consultant to Amgen, AstraZeneca, JanOne and Sanofi. Dr. Mehran has received research funding from Bayer and has been a consultant to Janssen, and she has also received research funding or been a consultant to several other companies.

SOURCE: Bonaca MP et al. ACC 20, Abstract 402-10.

 

A combined antithrombotic regimen of rivaroxaban plus aspirin was safe and effective for reducing ischemic events in patients with symptomatic peripheral artery disease who had just undergone peripheral artery revascularization in VOYAGER PAD, a multicenter randomized trial with nearly 6,600 patients.

Dr. Mark P. Bonaca

The study and its results were a groundbreaking advance for this patient population, who until now have had no evidence-based treatment available, Mark P. Bonaca, MD, said on March 28 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

The study design excluded a small percentage of patients (about 2%) because of their very high bleeding-risk history. Among the treated patients, in those who received a combination of 2.5 mg rivaroxaban twice daily plus 100 mg of aspirin daily, bleeding events were more common, compared with control patients who received aspirin alone. But the patients who received both drugs showed no excess of fatal bleeds or intracranial hemorrhages, and the rate of ischemic events prevented by rivaroxaban plus aspirin exceeded the excess rate of bleeds by three- to sixfold, depending on how bleeding episodes were defined, noted Dr. Bonaca, executive director of CPC Clinical Research and CPC Community Health, an academic research organization affiliated with the University of Colorado at Denver in Aurora.

Dr. Mark A. Creager

“This was a much anticipated and important trial. Those of us who treat patients with lower-limb peripheral artery disease have not had much evidence on how to treat these patients, particularly those who have just undergone revascularization. This trial gives us the evidence,” commented Mark A. Creager, MD, professor of medicine and director of the Heart and Vascular Center at Dartmouth-Hitchcock Medical Center in Lebanon, N.H. “The bleeding risk [from adding rivaroxaban treatment] was substantially less than the benefit from preventing major adverse limb events and major adverse cardiovascular events,” producing a “favorable balance” of benefit, compared with risk, Dr. Creager said in an interview. “In the right patients, the benefit greatly outweighed the risk.”

Dr. Joshua A. Beckman

“This was an incredible trial that will advance care,” commented Joshua A. Beckman, MD, professor of medicine and director of Vascular Medicine at Vanderbilt University in Nashville, Tenn. “The treatment was beneficial for patients across a range of symptom severity, from claudication to critical limb ischemia,” and the results expand the range of patients proven to benefit from the rivaroxaban plus aspirin combination from the types of patients with peripheral artery disease (PAD) enrolled in the COMPASS trial. That pivotal trial showed similar benefit from the dual-antithrombotic regimen, but in patients who had both coronary artery disease as well as atherosclerotic disease in at least one additional vascular bed, such as lower-limb arteries (N Engl J Med. 2017 Oct 5;377[14]:1319-30). In addition to “bringing acute limb ischemia to the cardiovascular community,” the results also identified a very useful time point in the clinical presentation of these patients for starting a combined rivaroxaban plus aspirin regimen: when patients are hospitalized for their revascularization procedure, said Dr. Beckman, a designated discussant for the report.



Among the 6,564 patients randomized in the study, about two-thirds underwent endovascular revascularization within 10 days before starting their study treatment, and the remaining third had undergone surgical revascularization. The study focused on patients “with symptomatic PAD but without known coronary artery disease,” noted Dr. Bonaca.

 

 

VOYAGER PAD trial

The VOYAGER PAD (Vascular Outcomes Study of Acetylsalicylic Acid Along With Rivaroxaban in Endovascular Or Surgical Limb Revascularization for Peripheral Artery Disease) trial enrolled patients during 2015-2018 at 534 sites in 34 countries. The study’s primary endpoint was a composite of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes, and was reduced during a median follow-up of 28 months from 19.9% with aspirin alone to 17.3% on the combined regimen, a 2.6% absolute difference and a 15% relative risk reduction that was statistically significant, an endpoint primarily driven by a reduction in acute limb ischemia. The primary safety endpoint was the rate of TIMI (Thrombolysis in Myocardial Infarction) major bleeds, which was 0.8% higher in the patients who received the anticoagulant, a 43% relative increase that just missed statistical significance. But that result demonstrated the small but important increased risk for bleeding events that the dual regimen produced in these patients, Dr. Bonaca said. Simultaneously with his report the findings also appeared in an article published online (N Engl J Med. 2020 Mar 28. doi: 10.1056/NEJMoa2000052).

Dr. Bonaca cautioned that one limitation of his report on the primary outcome of VOYAGER PAD is that the results of an important subgroup analysis won’t be known until a second report during the ACC online sessions on March 29, which will examine the impact that treatment with the antiplatelet drug clopidogrel had on both the efficacy and safety outcomes. Half of the enrolled patients received clopidogrel at the discretion of their treating physicians; addition or exclusion of concurrent clopidogrel treatment was outside of the study’s design. “Is efficacy the same with or without clopidogrel, and what is the bleeding cost,” especially in patients who receive three antithrombotic drugs? “It will be very important to understand,” Dr. Bonaca said.

Dr. Roxana Mehran

“Until now, we had no idea of what was the best antithrombotic strategy for patients after a successful peripheral vascular intervention.” VOYAGER PAD was “an unprecedented vascular study that addressed an unmet patient need,” commented Roxana Mehran, MD, a designated discussant for the study and professor of medicine and director of Interventional Cardiovascular Research at Mount Sinai Medical Center in New York.

VOYAGER PAD was sponsored by Bayer and Janssen, the companies that market rivaroxaban (Xarelto). The institution that Dr. Bonaca directs has received research funding from Bayer and Janssen, and also from Amgen, Aralez, AstraZeneca, Merck, Novo Nordisk, Pfizer, and Sanofi. Dr. Creager had no disclosures. Dr. Beckman has served as a data safety monitor for Bayer and for Novartis, and has been a consultant to Amgen, AstraZeneca, JanOne and Sanofi. Dr. Mehran has received research funding from Bayer and has been a consultant to Janssen, and she has also received research funding or been a consultant to several other companies.

SOURCE: Bonaca MP et al. ACC 20, Abstract 402-10.

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Key clinical point: Combined treatment with rivaroxaban plus aspirin safely reduced a composite measure of adverse ischemic events in PAD patients following lower-limb revascularization.

Major finding: The primary event outcome occurred in 17.3% of patients on rivaroxaban plus aspirin, and in 19.9% on aspirin alone.

Study details: VOYAGER PAD, a multicenter, international randomized trial with 6,564 patients.

Disclosures: VOYAGER PAD was sponsored by Bayer and Janssen, the companies that market rivaroxaban (Xarelto). The institution that Dr. Bonaca directs has received research funding from Bayer and Janssen, and also from Amgen, Aralez, AstraZeneca, Merck, Novo Nordisk, Pfizer, and Sanofi. Dr. Creager had no disclosures. Dr. Beckman has served as a data safety monitor for Bayer and for Novartis, and has been a consultant to Amgen, AstraZeneca, JanOne and Sanofi. Dr. Mehran has received research funding from Bayer and has been a consultant to Janssen, and she has also received research funding or been a consultant to several other companies.

Source: Bonaca MP. ACC 20, Abstract 402-10.

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Wuhan data link COVID-19 with myocardial damage

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The first data on myocardial injury linked with COVID-19 disease during the start of the pandemic in Wuhan, China serves as a “wake up call” for clinicians and the general public on what the United States and other Western countries can expect as the SARS-CoV-2 virus spreads and case numbers mount: a potentially “daunting” toll of deaths as an infection with a tendency to be most severe in patients with underlying cardiovascular disease hits populations that include large numbers of such patients.

Dr. Robert O. Bonow

“A consistent picture emerges” from two reports on a total of 603 COVID-19 patients treated at two academic hospitals in Wuhan, which described “remarkably similar characteristics of patients who develop myocardial injury” associated with their infection. “Patients who develop myocardial injury with COVID-19 have clinical evidence of higher acuity, with a higher incidence of acute respiratory distress syndrome and more frequent need for assisted ventilation than those without myocardial injury, and the patients who are more prone to have myocardial injury are “older patients with preexisting cardiovascular complications and diabetes,” Robert O. Bonow, MD, and coauthors wrote in an editorial published online (JAMA Cardiol. 2020 Mar 27. doi: 10.1001/jamacardio.2020.1105).

These new findings have special relevance to the United States and other Western countries because of their substantial numbers of elderly patients with cardiovascular diseases, said Dr. Bonow, professor of medicine at Northwestern University, Chicago, and coauthors.

One of the two reports cited in the editorial reviewed 416 patients hospitalized at Renmin Hospital in Wuhan during the period of Jan. 20 to Feb. 10, 2020, with confirmed COVID-19 disease, and found that 20% of the cohort had evidence of cardiac injury, defined as blood levels of the high-sensitivity troponin I cardiac biomarker above the 99th-percentile upper reference limit, regardless of new abnormalities in electrocardiography and echocardiography.

The analysis also showed that patients with myocardial injury had a significantly higher in-hospital mortality rate, 51%, compared with a 5% mortality rate among patients without myocardial injury, and among patients with myocardial injury those with elevated high-sensitivity troponin I had an even higher mortality rate (JAMA Cardiol. 2020 Mar 25. doi: 10.1001/jamacardio.2020.0950).

A second review of 187 confirmed COVID-19 cases at Seventh Hospital in Wuhan during the period of Jan. 23 to Feb. 23, 2020, showed similar findings, with a 28% prevalence of myocardial injury at admission based on an elevated level of plasma troponin T (TnT), and 35% had cardiovascular disease (CVD) including hypertension, coronary heart disease, and cardiomyopathy. Elevated TnT levels and CVD at entry each linked with substantially increased mortality. The incidence of death among patients with elevated TnT and no underlying CVD was 38% compared with 8% among patients without elevated TnT or underlying CVD. Among patients admitted with underlying CVD those who also had an elevated TnT had a 69% death rate during hospitalization compared with a 13% rate in those without TnT elevation (JAMA Cardiol. 2020 Mar 27. doi: 10.1001/jamacardio.2020.1017).



Dr. Bonow and coauthors noted that patients with chronic coronary artery disease have a heightened risk for developing acute coronary syndrome during acute infection, potentially resulting from a severe increase in myocardial demand during infection, or severe systemic inflammatory stress that could result in atherosclerotic plaque instability and rupture as well as vascular and myocardial inflammation.

In addition, patients with heart failure are prone to hemodynamic instability during severe infection. “Thus it is anticipated that patients with underlying cardiovascular diseases, which are more prevalent in older adults, would be susceptible to higher risks of adverse outcomes and death during the severe and aggressive inflammatory responses to COVID-19 than individuals who are younger and healthier,” they wrote.

They also cited the potential for acute or fulminant myocarditis as well as new-onset heart failure caused by the SARS-CoV-2 virus that causes COVID-19 disease based on experience with the related Middle East respiratory syndrome coronavirus. Another concerning observation is that the SARS-CoV-2 virus binds to the angiotensin-converting enzyme 2 protein on cell surfaces as its main entry receptor, “raising the possibility of direct viral infection of vascular endothelium and myocardium,” a process that itself could produce myocardial injury and myocarditis.

These new findings from COVID-19 patients in Wuhan represent early data from what has become a global pandemic, and raise questions about generalizability, but for the time being a key message from these early cases is that prevention of SARS-CoV-2 infection is paramount. “Until we know more, the populations described in these primary data reports should be most observant of strict hand hygiene, social distancing, and, where available, COVID-19 testing,” the authors said.

Dr. Bonow and coauthors had no disclosures.

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The first data on myocardial injury linked with COVID-19 disease during the start of the pandemic in Wuhan, China serves as a “wake up call” for clinicians and the general public on what the United States and other Western countries can expect as the SARS-CoV-2 virus spreads and case numbers mount: a potentially “daunting” toll of deaths as an infection with a tendency to be most severe in patients with underlying cardiovascular disease hits populations that include large numbers of such patients.

Dr. Robert O. Bonow

“A consistent picture emerges” from two reports on a total of 603 COVID-19 patients treated at two academic hospitals in Wuhan, which described “remarkably similar characteristics of patients who develop myocardial injury” associated with their infection. “Patients who develop myocardial injury with COVID-19 have clinical evidence of higher acuity, with a higher incidence of acute respiratory distress syndrome and more frequent need for assisted ventilation than those without myocardial injury, and the patients who are more prone to have myocardial injury are “older patients with preexisting cardiovascular complications and diabetes,” Robert O. Bonow, MD, and coauthors wrote in an editorial published online (JAMA Cardiol. 2020 Mar 27. doi: 10.1001/jamacardio.2020.1105).

These new findings have special relevance to the United States and other Western countries because of their substantial numbers of elderly patients with cardiovascular diseases, said Dr. Bonow, professor of medicine at Northwestern University, Chicago, and coauthors.

One of the two reports cited in the editorial reviewed 416 patients hospitalized at Renmin Hospital in Wuhan during the period of Jan. 20 to Feb. 10, 2020, with confirmed COVID-19 disease, and found that 20% of the cohort had evidence of cardiac injury, defined as blood levels of the high-sensitivity troponin I cardiac biomarker above the 99th-percentile upper reference limit, regardless of new abnormalities in electrocardiography and echocardiography.

The analysis also showed that patients with myocardial injury had a significantly higher in-hospital mortality rate, 51%, compared with a 5% mortality rate among patients without myocardial injury, and among patients with myocardial injury those with elevated high-sensitivity troponin I had an even higher mortality rate (JAMA Cardiol. 2020 Mar 25. doi: 10.1001/jamacardio.2020.0950).

A second review of 187 confirmed COVID-19 cases at Seventh Hospital in Wuhan during the period of Jan. 23 to Feb. 23, 2020, showed similar findings, with a 28% prevalence of myocardial injury at admission based on an elevated level of plasma troponin T (TnT), and 35% had cardiovascular disease (CVD) including hypertension, coronary heart disease, and cardiomyopathy. Elevated TnT levels and CVD at entry each linked with substantially increased mortality. The incidence of death among patients with elevated TnT and no underlying CVD was 38% compared with 8% among patients without elevated TnT or underlying CVD. Among patients admitted with underlying CVD those who also had an elevated TnT had a 69% death rate during hospitalization compared with a 13% rate in those without TnT elevation (JAMA Cardiol. 2020 Mar 27. doi: 10.1001/jamacardio.2020.1017).



Dr. Bonow and coauthors noted that patients with chronic coronary artery disease have a heightened risk for developing acute coronary syndrome during acute infection, potentially resulting from a severe increase in myocardial demand during infection, or severe systemic inflammatory stress that could result in atherosclerotic plaque instability and rupture as well as vascular and myocardial inflammation.

In addition, patients with heart failure are prone to hemodynamic instability during severe infection. “Thus it is anticipated that patients with underlying cardiovascular diseases, which are more prevalent in older adults, would be susceptible to higher risks of adverse outcomes and death during the severe and aggressive inflammatory responses to COVID-19 than individuals who are younger and healthier,” they wrote.

They also cited the potential for acute or fulminant myocarditis as well as new-onset heart failure caused by the SARS-CoV-2 virus that causes COVID-19 disease based on experience with the related Middle East respiratory syndrome coronavirus. Another concerning observation is that the SARS-CoV-2 virus binds to the angiotensin-converting enzyme 2 protein on cell surfaces as its main entry receptor, “raising the possibility of direct viral infection of vascular endothelium and myocardium,” a process that itself could produce myocardial injury and myocarditis.

These new findings from COVID-19 patients in Wuhan represent early data from what has become a global pandemic, and raise questions about generalizability, but for the time being a key message from these early cases is that prevention of SARS-CoV-2 infection is paramount. “Until we know more, the populations described in these primary data reports should be most observant of strict hand hygiene, social distancing, and, where available, COVID-19 testing,” the authors said.

Dr. Bonow and coauthors had no disclosures.

The first data on myocardial injury linked with COVID-19 disease during the start of the pandemic in Wuhan, China serves as a “wake up call” for clinicians and the general public on what the United States and other Western countries can expect as the SARS-CoV-2 virus spreads and case numbers mount: a potentially “daunting” toll of deaths as an infection with a tendency to be most severe in patients with underlying cardiovascular disease hits populations that include large numbers of such patients.

Dr. Robert O. Bonow

“A consistent picture emerges” from two reports on a total of 603 COVID-19 patients treated at two academic hospitals in Wuhan, which described “remarkably similar characteristics of patients who develop myocardial injury” associated with their infection. “Patients who develop myocardial injury with COVID-19 have clinical evidence of higher acuity, with a higher incidence of acute respiratory distress syndrome and more frequent need for assisted ventilation than those without myocardial injury, and the patients who are more prone to have myocardial injury are “older patients with preexisting cardiovascular complications and diabetes,” Robert O. Bonow, MD, and coauthors wrote in an editorial published online (JAMA Cardiol. 2020 Mar 27. doi: 10.1001/jamacardio.2020.1105).

These new findings have special relevance to the United States and other Western countries because of their substantial numbers of elderly patients with cardiovascular diseases, said Dr. Bonow, professor of medicine at Northwestern University, Chicago, and coauthors.

One of the two reports cited in the editorial reviewed 416 patients hospitalized at Renmin Hospital in Wuhan during the period of Jan. 20 to Feb. 10, 2020, with confirmed COVID-19 disease, and found that 20% of the cohort had evidence of cardiac injury, defined as blood levels of the high-sensitivity troponin I cardiac biomarker above the 99th-percentile upper reference limit, regardless of new abnormalities in electrocardiography and echocardiography.

The analysis also showed that patients with myocardial injury had a significantly higher in-hospital mortality rate, 51%, compared with a 5% mortality rate among patients without myocardial injury, and among patients with myocardial injury those with elevated high-sensitivity troponin I had an even higher mortality rate (JAMA Cardiol. 2020 Mar 25. doi: 10.1001/jamacardio.2020.0950).

A second review of 187 confirmed COVID-19 cases at Seventh Hospital in Wuhan during the period of Jan. 23 to Feb. 23, 2020, showed similar findings, with a 28% prevalence of myocardial injury at admission based on an elevated level of plasma troponin T (TnT), and 35% had cardiovascular disease (CVD) including hypertension, coronary heart disease, and cardiomyopathy. Elevated TnT levels and CVD at entry each linked with substantially increased mortality. The incidence of death among patients with elevated TnT and no underlying CVD was 38% compared with 8% among patients without elevated TnT or underlying CVD. Among patients admitted with underlying CVD those who also had an elevated TnT had a 69% death rate during hospitalization compared with a 13% rate in those without TnT elevation (JAMA Cardiol. 2020 Mar 27. doi: 10.1001/jamacardio.2020.1017).



Dr. Bonow and coauthors noted that patients with chronic coronary artery disease have a heightened risk for developing acute coronary syndrome during acute infection, potentially resulting from a severe increase in myocardial demand during infection, or severe systemic inflammatory stress that could result in atherosclerotic plaque instability and rupture as well as vascular and myocardial inflammation.

In addition, patients with heart failure are prone to hemodynamic instability during severe infection. “Thus it is anticipated that patients with underlying cardiovascular diseases, which are more prevalent in older adults, would be susceptible to higher risks of adverse outcomes and death during the severe and aggressive inflammatory responses to COVID-19 than individuals who are younger and healthier,” they wrote.

They also cited the potential for acute or fulminant myocarditis as well as new-onset heart failure caused by the SARS-CoV-2 virus that causes COVID-19 disease based on experience with the related Middle East respiratory syndrome coronavirus. Another concerning observation is that the SARS-CoV-2 virus binds to the angiotensin-converting enzyme 2 protein on cell surfaces as its main entry receptor, “raising the possibility of direct viral infection of vascular endothelium and myocardium,” a process that itself could produce myocardial injury and myocarditis.

These new findings from COVID-19 patients in Wuhan represent early data from what has become a global pandemic, and raise questions about generalizability, but for the time being a key message from these early cases is that prevention of SARS-CoV-2 infection is paramount. “Until we know more, the populations described in these primary data reports should be most observant of strict hand hygiene, social distancing, and, where available, COVID-19 testing,” the authors said.

Dr. Bonow and coauthors had no disclosures.

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COVID-19 critical care guideline offers support for frontline clinicians

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Changed
Thu, 08/26/2021 - 16:18

The Society of Critical Care Medicine released its first set of guidelines for managing critically ill patients with novel coronavirus disease (COVID-19) on March 20, 2020.

Dr. Mangala Narasimhan

The 49 recommendations and statements it included are geared to “support hospital clinicians managing critically ill adults with COVID-19 in the ICU. The target users of this guideline are frontline clinicians, allied health professionals, and policy makers involved in the care of patients with COVID-19 in the ICU,” said the document, written by a panel of 36 experts organized by the Surviving Sepsis Campaign, a joint program of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine.

The document divides the recommendations into four categories: infection control, which includes 3 “best-practice” statements and 5 “weak” recommendations; hemodynamics with 2 “strong” recommendations and 13 weak ones; ventilation, with 1 best-practice statement, 6 strong recommendations, and 12 weak recommendations; and therapy with 7 weak recommendations. The guidelines also included five management questions considered by the writing panel without arriving at a recommendation because of insufficient evidence.

 


 

Useful guide nonspecialists

Some critical care medicine physicians saw the new guidelines as offering no surprises, but providing a very useful resource to guide management, especially for clinicians who may become involved in caring for COVID-19 patients despite having little experience caring for patients with acute respiratory distress syndrome (ARDS).

“For those of us who manage ARDS patients all the time, this is not a lot of new information, but many critically ill COVID-19 patients are now being cared for by physicians who have not cared for these patients before,” commented Mangala Narasimhan, DO, FCCP, a critical care medicine physician at Long Island Jewish Medical Center in New Hyde Park, N.Y. In fact, Dr, Narasimhan and associates took the new guidelines soon after their release and used them to create a one-page summary sheet to give to all their colleagues who are now seeing COVID-19 patients, she said in an interview. “The guidelines are very important for clinicians who are suddenly taking care of a roomful of patients with ARDS.”

“A lot of people want to know this information,” agreed David M. Ferraro, MD, FCCP, a pulmonologist and critical care medicine physician at National Jewish Health in Denver.

Dr. David M. Ferraro


Perhaps the only potentially controversial aspect of the guidelines are a couple of weak recommendations that suggest using a high-flow nasal cannula (HFNC) rather than noninvasive positive pressure ventilation (NIPPV) in patients with acute hypoxemic respiratory failure who have not fully responded to conventional oxygen therapy. “This is controversial, and some of my colleagues are debating this,” said Dr. Narasimhan, but she noted that her clinic has decided to follow the recommended preference for HFNC, which seemed to have modest advantages over NIPPV in a recent meta-analysis (Intensive Care Med. 2019 May;45[5]:563-72).

Another issue with NIPPV is the higher risk for viral dispersion it seems to have, compared with a HFNC, said Dr. Ferraro. If a patient’s mask comes off during NIPPV, it creates a substantial risk for aerosolization of virus. That risk is likely lower with HFNC, especially a HFNC system that uses a small cannula without heating or humidification of the gas flow. “I’d recommend against NIPPV,” Dr. Ferraro said.



He also highlighted the value of quickly forgoing continued use of either of these ventilatory approaches in a declining patient and having a low threshold to switch to intubation. “Many clinicians now favor erring on the side of early intubation,” he noted, an approach that the new guidelines endorsed in a best-practice statement: “In adults with COVID-19 receiving NIPPV or HFNC we recommend close monitoring for worsening respiratory status and early intubation in a controlled setting if worsening occurs.”

One aspect of the COVID-19 pandemic that the new guidelines don’t address are some of the challenges being faced from skyrocketing numbers of patients and inadequate supplies and manpower to meet their acute clinical needs. “We need recommendations on how systems should manage when they are overwhelmed,” commented Dr. Ferraro, an omission that he also saw in the COVID-19 management guidance released on March 13, 2020, by the World Health Organization.

“Neither document gets into this in depth, but that wasn’t in their scope,” Dr. Ferraro acknowledged. He said that recommendations on how to deal with scarce resources, inadequate staffing, and the health of clinicians are probably best handled on a state or local level rather than trying to create recommendations that are applicable to the entire U.S. health system.

Dr. Narasimhan and Dr. Ferraro reported that they had no disclosures.

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The Society of Critical Care Medicine released its first set of guidelines for managing critically ill patients with novel coronavirus disease (COVID-19) on March 20, 2020.

Dr. Mangala Narasimhan

The 49 recommendations and statements it included are geared to “support hospital clinicians managing critically ill adults with COVID-19 in the ICU. The target users of this guideline are frontline clinicians, allied health professionals, and policy makers involved in the care of patients with COVID-19 in the ICU,” said the document, written by a panel of 36 experts organized by the Surviving Sepsis Campaign, a joint program of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine.

The document divides the recommendations into four categories: infection control, which includes 3 “best-practice” statements and 5 “weak” recommendations; hemodynamics with 2 “strong” recommendations and 13 weak ones; ventilation, with 1 best-practice statement, 6 strong recommendations, and 12 weak recommendations; and therapy with 7 weak recommendations. The guidelines also included five management questions considered by the writing panel without arriving at a recommendation because of insufficient evidence.

 


 

Useful guide nonspecialists

Some critical care medicine physicians saw the new guidelines as offering no surprises, but providing a very useful resource to guide management, especially for clinicians who may become involved in caring for COVID-19 patients despite having little experience caring for patients with acute respiratory distress syndrome (ARDS).

“For those of us who manage ARDS patients all the time, this is not a lot of new information, but many critically ill COVID-19 patients are now being cared for by physicians who have not cared for these patients before,” commented Mangala Narasimhan, DO, FCCP, a critical care medicine physician at Long Island Jewish Medical Center in New Hyde Park, N.Y. In fact, Dr, Narasimhan and associates took the new guidelines soon after their release and used them to create a one-page summary sheet to give to all their colleagues who are now seeing COVID-19 patients, she said in an interview. “The guidelines are very important for clinicians who are suddenly taking care of a roomful of patients with ARDS.”

“A lot of people want to know this information,” agreed David M. Ferraro, MD, FCCP, a pulmonologist and critical care medicine physician at National Jewish Health in Denver.

Dr. David M. Ferraro


Perhaps the only potentially controversial aspect of the guidelines are a couple of weak recommendations that suggest using a high-flow nasal cannula (HFNC) rather than noninvasive positive pressure ventilation (NIPPV) in patients with acute hypoxemic respiratory failure who have not fully responded to conventional oxygen therapy. “This is controversial, and some of my colleagues are debating this,” said Dr. Narasimhan, but she noted that her clinic has decided to follow the recommended preference for HFNC, which seemed to have modest advantages over NIPPV in a recent meta-analysis (Intensive Care Med. 2019 May;45[5]:563-72).

Another issue with NIPPV is the higher risk for viral dispersion it seems to have, compared with a HFNC, said Dr. Ferraro. If a patient’s mask comes off during NIPPV, it creates a substantial risk for aerosolization of virus. That risk is likely lower with HFNC, especially a HFNC system that uses a small cannula without heating or humidification of the gas flow. “I’d recommend against NIPPV,” Dr. Ferraro said.



He also highlighted the value of quickly forgoing continued use of either of these ventilatory approaches in a declining patient and having a low threshold to switch to intubation. “Many clinicians now favor erring on the side of early intubation,” he noted, an approach that the new guidelines endorsed in a best-practice statement: “In adults with COVID-19 receiving NIPPV or HFNC we recommend close monitoring for worsening respiratory status and early intubation in a controlled setting if worsening occurs.”

One aspect of the COVID-19 pandemic that the new guidelines don’t address are some of the challenges being faced from skyrocketing numbers of patients and inadequate supplies and manpower to meet their acute clinical needs. “We need recommendations on how systems should manage when they are overwhelmed,” commented Dr. Ferraro, an omission that he also saw in the COVID-19 management guidance released on March 13, 2020, by the World Health Organization.

“Neither document gets into this in depth, but that wasn’t in their scope,” Dr. Ferraro acknowledged. He said that recommendations on how to deal with scarce resources, inadequate staffing, and the health of clinicians are probably best handled on a state or local level rather than trying to create recommendations that are applicable to the entire U.S. health system.

Dr. Narasimhan and Dr. Ferraro reported that they had no disclosures.

The Society of Critical Care Medicine released its first set of guidelines for managing critically ill patients with novel coronavirus disease (COVID-19) on March 20, 2020.

Dr. Mangala Narasimhan

The 49 recommendations and statements it included are geared to “support hospital clinicians managing critically ill adults with COVID-19 in the ICU. The target users of this guideline are frontline clinicians, allied health professionals, and policy makers involved in the care of patients with COVID-19 in the ICU,” said the document, written by a panel of 36 experts organized by the Surviving Sepsis Campaign, a joint program of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine.

The document divides the recommendations into four categories: infection control, which includes 3 “best-practice” statements and 5 “weak” recommendations; hemodynamics with 2 “strong” recommendations and 13 weak ones; ventilation, with 1 best-practice statement, 6 strong recommendations, and 12 weak recommendations; and therapy with 7 weak recommendations. The guidelines also included five management questions considered by the writing panel without arriving at a recommendation because of insufficient evidence.

 


 

Useful guide nonspecialists

Some critical care medicine physicians saw the new guidelines as offering no surprises, but providing a very useful resource to guide management, especially for clinicians who may become involved in caring for COVID-19 patients despite having little experience caring for patients with acute respiratory distress syndrome (ARDS).

“For those of us who manage ARDS patients all the time, this is not a lot of new information, but many critically ill COVID-19 patients are now being cared for by physicians who have not cared for these patients before,” commented Mangala Narasimhan, DO, FCCP, a critical care medicine physician at Long Island Jewish Medical Center in New Hyde Park, N.Y. In fact, Dr, Narasimhan and associates took the new guidelines soon after their release and used them to create a one-page summary sheet to give to all their colleagues who are now seeing COVID-19 patients, she said in an interview. “The guidelines are very important for clinicians who are suddenly taking care of a roomful of patients with ARDS.”

“A lot of people want to know this information,” agreed David M. Ferraro, MD, FCCP, a pulmonologist and critical care medicine physician at National Jewish Health in Denver.

Dr. David M. Ferraro


Perhaps the only potentially controversial aspect of the guidelines are a couple of weak recommendations that suggest using a high-flow nasal cannula (HFNC) rather than noninvasive positive pressure ventilation (NIPPV) in patients with acute hypoxemic respiratory failure who have not fully responded to conventional oxygen therapy. “This is controversial, and some of my colleagues are debating this,” said Dr. Narasimhan, but she noted that her clinic has decided to follow the recommended preference for HFNC, which seemed to have modest advantages over NIPPV in a recent meta-analysis (Intensive Care Med. 2019 May;45[5]:563-72).

Another issue with NIPPV is the higher risk for viral dispersion it seems to have, compared with a HFNC, said Dr. Ferraro. If a patient’s mask comes off during NIPPV, it creates a substantial risk for aerosolization of virus. That risk is likely lower with HFNC, especially a HFNC system that uses a small cannula without heating or humidification of the gas flow. “I’d recommend against NIPPV,” Dr. Ferraro said.



He also highlighted the value of quickly forgoing continued use of either of these ventilatory approaches in a declining patient and having a low threshold to switch to intubation. “Many clinicians now favor erring on the side of early intubation,” he noted, an approach that the new guidelines endorsed in a best-practice statement: “In adults with COVID-19 receiving NIPPV or HFNC we recommend close monitoring for worsening respiratory status and early intubation in a controlled setting if worsening occurs.”

One aspect of the COVID-19 pandemic that the new guidelines don’t address are some of the challenges being faced from skyrocketing numbers of patients and inadequate supplies and manpower to meet their acute clinical needs. “We need recommendations on how systems should manage when they are overwhelmed,” commented Dr. Ferraro, an omission that he also saw in the COVID-19 management guidance released on March 13, 2020, by the World Health Organization.

“Neither document gets into this in depth, but that wasn’t in their scope,” Dr. Ferraro acknowledged. He said that recommendations on how to deal with scarce resources, inadequate staffing, and the health of clinicians are probably best handled on a state or local level rather than trying to create recommendations that are applicable to the entire U.S. health system.

Dr. Narasimhan and Dr. Ferraro reported that they had no disclosures.

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Intracranial artery stenting shows promising 1-year results

Article Type
Changed
Tue, 07/21/2020 - 14:33

Limiting intracranial artery stenting to stroke patients who fit the tightly defined labeling the device has may have minimized periprocedural complications, as shown in the WEAVE trial results reported in 2019, but 1-year follow-up of most of the WEAVE patients also showed that intracranial stenting remains plagued by another issue, frequent restenosis.

Mitchel L. Zoler/MDedge News
Dr. Michael J. Alexander

One-year after 129 patients received an intracranial stent that’s already on the U.S. market for treating severe atherosclerotic disease following an ischemic stroke, their incidence of death or repeat stroke was 9%, low enough to suggest benefit compared with historic control patients who were medically managed and had a 12% 1-year rate of death or stroke. This signal of incremental benefit from intracranial stenting may help spark renewed interest in an intervention that was largely forsaken in recent years because of safety concerns.
 

Assessing restenosis frequency

“Stenting seemed to confer some protection against severe or fatal strokes” in a study that provided “the largest 1-year follow-up of stenting” for intracranial atherosclerotic disease, the trigger for roughly 10% of all U.S. stroke cases, Michael J. Alexander, MD, said at the International Stroke Conference, sponsored by the American Heart Association.

What 1-year follow-up highlighted was the restenosis frequency, based on imaging follow-up for 107 of these 129 patients who had received a Wingspan nitinol, self-expanding stent. Seven patients developed symptomatic restenosis in the region of stent placement, and another 11 patients had asymptomatic restenosis that occluded at least 70% of the stented artery, a total 1-year restenosis rate of 18/107 (17%), reported Dr. Alexander, professor of neurosurgery and director of the Neurovascular Center at Cedars-Sinai Medical Center in Los Angeles. The mean time to detection of restenosis was 5 months, with a range of 1-11 months.
 

Intracranial stenting falls out of favor

The tested Wingspan stent first received Food and Drug Administration approval for intracranial artery placement in 2005, and then in August 2012 the agency tightened the labeled indication to a much smaller, more specifically defined group of patients: those 22-80 years old, with 70%-99% stenosis in a cerebral artery, with a history of at least two strokes, with stent placement timed more than 7 days following the most recent stroke, and refractory to medical therapy. This 2012 label change came in response to a concerning rate of periprocedural complications in patients who received intracrania artery stents as part of a study reported in 2011 that included many patients with clinical characteristics that fell outside the limits the agency later set in 2012. Results from the SAMMPRIS (Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) trial showed that among 451 randomized patients the 224 assigned to stenting had a 15% 30-day rate of death or stroke, compared with a 6% rate among control patients who did not receive a stent, a statistically significant difference that led to early stopping of the trial (New Engl J Med. 2011 Sep 15;365[11]:993-1003). At least half of the patients who received a stent in SAMMPRIS were 7 or fewer days out from their index event, a majority had either a single prior stroke or transient ischemic attack as their index event, and many had not been established as refractory to medical management.

Mitchel L. Zoler/MDedge News
Dr. Louise D. McCullough

The SAMMPRIS results and the subsequent relabeling of the Wingspan stent by the FDA had two consequences. First came a steep drop in the use of intracranial stenting. After SAMMPRIS, vascular neurologists “abandoned the stent; no one does intracranial stenting” today, commented Louise D. McCullough, MD, professor and chair of neurology at the University of Texas Health Science Center at Houston. The second consequence was an FDA mandate to run a new randomized study to reassess the periprocedural complications when clinicians placed the Wingspan intracranial stent in patients who fully matched the revised 2012 labeling.

That mandated study was the WEAVE (Post Market Surveillance Study of the Wingspan Stent System) trial, which enrolled 152 patients at 24 U.S. sites in a single-arm study, and found a 2.6% rate of death or stroke during the 30 days following intervention that beat the 4% benchmark rate prespecified in the trial’s design (Stroke. 2019 Apr;50[4]:889-94). The WEAVE findings provided even more evidence of the need for the tight labeling the device received in 2012. A safety communication from the FDA in April 2019 noted that an additional 46 patients received an intracranial artery stent during WEAVE despite falling outside the 2012 labeled indications, and this off-label group had a 24% incidence of periprocedural complications, compared with the 2.6% rate in the on-label group. The FDA’s statement reaffirmed the labeling restrictions and highlighted additional cautions and recommendations for using the device.
 

The WOVEN study

The 1-year follow-up of the WEAVE patients, an extension called the WOVEN (Wingspan One Year Vascular Imaging Events and Neurologic Outcomes) study, was investigator initiated with no commercial funding and included 129 of the original on-label patients (85%) at 15 of the original 24 participating centers.

In addition to the data collected in WOVEN on restenosis rates, follow-up tallied seven patients with a stroke in the vascular territory of the stent during the period that began 30 days after the procedure (when the WEAVE follow-up finished) and continued through 12 months, with no neurologic deaths. When combined with the 4 periprocedural events that occurred during WEAVE, the final WOVEN tally was 11 total events in 129 patients followed for 1 year (9%). Because WEAVE and WOVEN included no control patients, Dr. Alexander compared this 1-year incidence rate with the 12% rate among medically managed control patients in SAMMPRIS.



According to Dr. Alexander, the next step in the path to rehabilitating a clinical role for intracranial stenting is a new randomized study that compares stenting used exclusively to the 2012 labeling with medical management in high-risk patients, those with hemodynamic compromise.

Encouraging data, but is it compelling?

“There may be a benefit” from intracranial stenting, but “we need a larger trial to convince people” said Dr. McCullough. The WEAVE and new WOVEN findings provide a “signal that stenting may be better than medical therapy, but this was only in just over 100 patients. We’ll need a larger study,” she said in an interview. The findings also reinforced that restenosis remains a challenge for intracranial artery stenting.

“Intracranial atherosclerosis is very difficult to treat, and we need new strategies for these patients.” The WEAVE and WOVEN results “suggest that while the restenosis rate may be high, it may also be manageable.” Delaying stent placement to no sooner than 8 days after a stroke may be a key step for improving safety, but new approaches are also need to minimize the restenosis risk, Dr. McCullough noted.

WEAVE was sponsored by Stryker Neurovascular, the company that markets the Wingspan intracranial artery stent. WOVEN received no commercial funding. Dr. Alexander has been a consultant to Stryker Neurovascular. Dr. McCullough had no disclosures.

SOURCE: Alexander MJ et al. International Stroke Conference, Abstract LB4.

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Limiting intracranial artery stenting to stroke patients who fit the tightly defined labeling the device has may have minimized periprocedural complications, as shown in the WEAVE trial results reported in 2019, but 1-year follow-up of most of the WEAVE patients also showed that intracranial stenting remains plagued by another issue, frequent restenosis.

Mitchel L. Zoler/MDedge News
Dr. Michael J. Alexander

One-year after 129 patients received an intracranial stent that’s already on the U.S. market for treating severe atherosclerotic disease following an ischemic stroke, their incidence of death or repeat stroke was 9%, low enough to suggest benefit compared with historic control patients who were medically managed and had a 12% 1-year rate of death or stroke. This signal of incremental benefit from intracranial stenting may help spark renewed interest in an intervention that was largely forsaken in recent years because of safety concerns.
 

Assessing restenosis frequency

“Stenting seemed to confer some protection against severe or fatal strokes” in a study that provided “the largest 1-year follow-up of stenting” for intracranial atherosclerotic disease, the trigger for roughly 10% of all U.S. stroke cases, Michael J. Alexander, MD, said at the International Stroke Conference, sponsored by the American Heart Association.

What 1-year follow-up highlighted was the restenosis frequency, based on imaging follow-up for 107 of these 129 patients who had received a Wingspan nitinol, self-expanding stent. Seven patients developed symptomatic restenosis in the region of stent placement, and another 11 patients had asymptomatic restenosis that occluded at least 70% of the stented artery, a total 1-year restenosis rate of 18/107 (17%), reported Dr. Alexander, professor of neurosurgery and director of the Neurovascular Center at Cedars-Sinai Medical Center in Los Angeles. The mean time to detection of restenosis was 5 months, with a range of 1-11 months.
 

Intracranial stenting falls out of favor

The tested Wingspan stent first received Food and Drug Administration approval for intracranial artery placement in 2005, and then in August 2012 the agency tightened the labeled indication to a much smaller, more specifically defined group of patients: those 22-80 years old, with 70%-99% stenosis in a cerebral artery, with a history of at least two strokes, with stent placement timed more than 7 days following the most recent stroke, and refractory to medical therapy. This 2012 label change came in response to a concerning rate of periprocedural complications in patients who received intracrania artery stents as part of a study reported in 2011 that included many patients with clinical characteristics that fell outside the limits the agency later set in 2012. Results from the SAMMPRIS (Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) trial showed that among 451 randomized patients the 224 assigned to stenting had a 15% 30-day rate of death or stroke, compared with a 6% rate among control patients who did not receive a stent, a statistically significant difference that led to early stopping of the trial (New Engl J Med. 2011 Sep 15;365[11]:993-1003). At least half of the patients who received a stent in SAMMPRIS were 7 or fewer days out from their index event, a majority had either a single prior stroke or transient ischemic attack as their index event, and many had not been established as refractory to medical management.

Mitchel L. Zoler/MDedge News
Dr. Louise D. McCullough

The SAMMPRIS results and the subsequent relabeling of the Wingspan stent by the FDA had two consequences. First came a steep drop in the use of intracranial stenting. After SAMMPRIS, vascular neurologists “abandoned the stent; no one does intracranial stenting” today, commented Louise D. McCullough, MD, professor and chair of neurology at the University of Texas Health Science Center at Houston. The second consequence was an FDA mandate to run a new randomized study to reassess the periprocedural complications when clinicians placed the Wingspan intracranial stent in patients who fully matched the revised 2012 labeling.

That mandated study was the WEAVE (Post Market Surveillance Study of the Wingspan Stent System) trial, which enrolled 152 patients at 24 U.S. sites in a single-arm study, and found a 2.6% rate of death or stroke during the 30 days following intervention that beat the 4% benchmark rate prespecified in the trial’s design (Stroke. 2019 Apr;50[4]:889-94). The WEAVE findings provided even more evidence of the need for the tight labeling the device received in 2012. A safety communication from the FDA in April 2019 noted that an additional 46 patients received an intracranial artery stent during WEAVE despite falling outside the 2012 labeled indications, and this off-label group had a 24% incidence of periprocedural complications, compared with the 2.6% rate in the on-label group. The FDA’s statement reaffirmed the labeling restrictions and highlighted additional cautions and recommendations for using the device.
 

The WOVEN study

The 1-year follow-up of the WEAVE patients, an extension called the WOVEN (Wingspan One Year Vascular Imaging Events and Neurologic Outcomes) study, was investigator initiated with no commercial funding and included 129 of the original on-label patients (85%) at 15 of the original 24 participating centers.

In addition to the data collected in WOVEN on restenosis rates, follow-up tallied seven patients with a stroke in the vascular territory of the stent during the period that began 30 days after the procedure (when the WEAVE follow-up finished) and continued through 12 months, with no neurologic deaths. When combined with the 4 periprocedural events that occurred during WEAVE, the final WOVEN tally was 11 total events in 129 patients followed for 1 year (9%). Because WEAVE and WOVEN included no control patients, Dr. Alexander compared this 1-year incidence rate with the 12% rate among medically managed control patients in SAMMPRIS.



According to Dr. Alexander, the next step in the path to rehabilitating a clinical role for intracranial stenting is a new randomized study that compares stenting used exclusively to the 2012 labeling with medical management in high-risk patients, those with hemodynamic compromise.

Encouraging data, but is it compelling?

“There may be a benefit” from intracranial stenting, but “we need a larger trial to convince people” said Dr. McCullough. The WEAVE and new WOVEN findings provide a “signal that stenting may be better than medical therapy, but this was only in just over 100 patients. We’ll need a larger study,” she said in an interview. The findings also reinforced that restenosis remains a challenge for intracranial artery stenting.

“Intracranial atherosclerosis is very difficult to treat, and we need new strategies for these patients.” The WEAVE and WOVEN results “suggest that while the restenosis rate may be high, it may also be manageable.” Delaying stent placement to no sooner than 8 days after a stroke may be a key step for improving safety, but new approaches are also need to minimize the restenosis risk, Dr. McCullough noted.

WEAVE was sponsored by Stryker Neurovascular, the company that markets the Wingspan intracranial artery stent. WOVEN received no commercial funding. Dr. Alexander has been a consultant to Stryker Neurovascular. Dr. McCullough had no disclosures.

SOURCE: Alexander MJ et al. International Stroke Conference, Abstract LB4.

Limiting intracranial artery stenting to stroke patients who fit the tightly defined labeling the device has may have minimized periprocedural complications, as shown in the WEAVE trial results reported in 2019, but 1-year follow-up of most of the WEAVE patients also showed that intracranial stenting remains plagued by another issue, frequent restenosis.

Mitchel L. Zoler/MDedge News
Dr. Michael J. Alexander

One-year after 129 patients received an intracranial stent that’s already on the U.S. market for treating severe atherosclerotic disease following an ischemic stroke, their incidence of death or repeat stroke was 9%, low enough to suggest benefit compared with historic control patients who were medically managed and had a 12% 1-year rate of death or stroke. This signal of incremental benefit from intracranial stenting may help spark renewed interest in an intervention that was largely forsaken in recent years because of safety concerns.
 

Assessing restenosis frequency

“Stenting seemed to confer some protection against severe or fatal strokes” in a study that provided “the largest 1-year follow-up of stenting” for intracranial atherosclerotic disease, the trigger for roughly 10% of all U.S. stroke cases, Michael J. Alexander, MD, said at the International Stroke Conference, sponsored by the American Heart Association.

What 1-year follow-up highlighted was the restenosis frequency, based on imaging follow-up for 107 of these 129 patients who had received a Wingspan nitinol, self-expanding stent. Seven patients developed symptomatic restenosis in the region of stent placement, and another 11 patients had asymptomatic restenosis that occluded at least 70% of the stented artery, a total 1-year restenosis rate of 18/107 (17%), reported Dr. Alexander, professor of neurosurgery and director of the Neurovascular Center at Cedars-Sinai Medical Center in Los Angeles. The mean time to detection of restenosis was 5 months, with a range of 1-11 months.
 

Intracranial stenting falls out of favor

The tested Wingspan stent first received Food and Drug Administration approval for intracranial artery placement in 2005, and then in August 2012 the agency tightened the labeled indication to a much smaller, more specifically defined group of patients: those 22-80 years old, with 70%-99% stenosis in a cerebral artery, with a history of at least two strokes, with stent placement timed more than 7 days following the most recent stroke, and refractory to medical therapy. This 2012 label change came in response to a concerning rate of periprocedural complications in patients who received intracrania artery stents as part of a study reported in 2011 that included many patients with clinical characteristics that fell outside the limits the agency later set in 2012. Results from the SAMMPRIS (Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) trial showed that among 451 randomized patients the 224 assigned to stenting had a 15% 30-day rate of death or stroke, compared with a 6% rate among control patients who did not receive a stent, a statistically significant difference that led to early stopping of the trial (New Engl J Med. 2011 Sep 15;365[11]:993-1003). At least half of the patients who received a stent in SAMMPRIS were 7 or fewer days out from their index event, a majority had either a single prior stroke or transient ischemic attack as their index event, and many had not been established as refractory to medical management.

Mitchel L. Zoler/MDedge News
Dr. Louise D. McCullough

The SAMMPRIS results and the subsequent relabeling of the Wingspan stent by the FDA had two consequences. First came a steep drop in the use of intracranial stenting. After SAMMPRIS, vascular neurologists “abandoned the stent; no one does intracranial stenting” today, commented Louise D. McCullough, MD, professor and chair of neurology at the University of Texas Health Science Center at Houston. The second consequence was an FDA mandate to run a new randomized study to reassess the periprocedural complications when clinicians placed the Wingspan intracranial stent in patients who fully matched the revised 2012 labeling.

That mandated study was the WEAVE (Post Market Surveillance Study of the Wingspan Stent System) trial, which enrolled 152 patients at 24 U.S. sites in a single-arm study, and found a 2.6% rate of death or stroke during the 30 days following intervention that beat the 4% benchmark rate prespecified in the trial’s design (Stroke. 2019 Apr;50[4]:889-94). The WEAVE findings provided even more evidence of the need for the tight labeling the device received in 2012. A safety communication from the FDA in April 2019 noted that an additional 46 patients received an intracranial artery stent during WEAVE despite falling outside the 2012 labeled indications, and this off-label group had a 24% incidence of periprocedural complications, compared with the 2.6% rate in the on-label group. The FDA’s statement reaffirmed the labeling restrictions and highlighted additional cautions and recommendations for using the device.
 

The WOVEN study

The 1-year follow-up of the WEAVE patients, an extension called the WOVEN (Wingspan One Year Vascular Imaging Events and Neurologic Outcomes) study, was investigator initiated with no commercial funding and included 129 of the original on-label patients (85%) at 15 of the original 24 participating centers.

In addition to the data collected in WOVEN on restenosis rates, follow-up tallied seven patients with a stroke in the vascular territory of the stent during the period that began 30 days after the procedure (when the WEAVE follow-up finished) and continued through 12 months, with no neurologic deaths. When combined with the 4 periprocedural events that occurred during WEAVE, the final WOVEN tally was 11 total events in 129 patients followed for 1 year (9%). Because WEAVE and WOVEN included no control patients, Dr. Alexander compared this 1-year incidence rate with the 12% rate among medically managed control patients in SAMMPRIS.



According to Dr. Alexander, the next step in the path to rehabilitating a clinical role for intracranial stenting is a new randomized study that compares stenting used exclusively to the 2012 labeling with medical management in high-risk patients, those with hemodynamic compromise.

Encouraging data, but is it compelling?

“There may be a benefit” from intracranial stenting, but “we need a larger trial to convince people” said Dr. McCullough. The WEAVE and new WOVEN findings provide a “signal that stenting may be better than medical therapy, but this was only in just over 100 patients. We’ll need a larger study,” she said in an interview. The findings also reinforced that restenosis remains a challenge for intracranial artery stenting.

“Intracranial atherosclerosis is very difficult to treat, and we need new strategies for these patients.” The WEAVE and WOVEN results “suggest that while the restenosis rate may be high, it may also be manageable.” Delaying stent placement to no sooner than 8 days after a stroke may be a key step for improving safety, but new approaches are also need to minimize the restenosis risk, Dr. McCullough noted.

WEAVE was sponsored by Stryker Neurovascular, the company that markets the Wingspan intracranial artery stent. WOVEN received no commercial funding. Dr. Alexander has been a consultant to Stryker Neurovascular. Dr. McCullough had no disclosures.

SOURCE: Alexander MJ et al. International Stroke Conference, Abstract LB4.

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COVID-19: U.S. cardiology groups reaffirm continued use of RAAS-active drugs

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Thu, 08/26/2021 - 16:20

Controversy continued over the potential effect of drugs that interfere with the renin-angiotensin-aldosterone system via the angiotensin-converting enzymes (ACE) may have on exacerbating infection with the SARS-CoV-2 virus that causes COVID-19.

A joint statement from the American Heart Association, American College of Cardiology, and the Heart Failure Society of America on March 17 gave full, unqualified support to maintaining patients on drugs that work this way, specifically the ACE inhibitors and angiotensin-receptor blockers (ARBs), which together form a long-standing cornerstone of treatment for hypertension, heart failure, and ischemic heart disease.

The three societies “recommend continuation” of ACE inhibitors or ARBs “for all patients already prescribed.” The statement went on to say that patients already diagnosed with a COVID-19 infection “should be fully evaluated before adding or removing any treatments, and any changes to their treatment should be based on the latest scientific evidence and shared decision making with their physician and health care team.”

“We understand the concern – as it has become clear that people with cardiovascular disease are at much higher risk of serious complications including death from COVID-19. However, we have reviewed the latest research – the evidence does not confirm the need to discontinue ACE inhibitors or ARBs, and we strongly recommend all physicians to consider the individual needs of each patient before making any changes to ACE-inhibitor or ARB treatment regimens,” said Robert A. Harrington, MD, president of the American Heart Association and professor and chair of medicine at Stanford (Calif.) University, in the statement.

“There are no experimental or clinical data demonstrating beneficial or adverse outcomes among COVID-19 patients using ACE-inhibitor or ARB medications,” added Richard J. Kovacs, MD, president of the American College of Cardiology and professor of cardiology at Indiana University in Indianapolis.



The “latest research” referred to in the statement likely focuses on a report that had appeared less than a week earlier in a British journal that hypothesized a possible increase in the susceptibility of human epithelial cells of the lungs, intestine, kidneys, and blood vessels exposed to these or certain other drugs, like the thiazolidinedione oral diabetes drugs or ibuprofen, because they cause up-regulation of the ACE2 protein in cell membranes, and ACE2 is the primary cell-surface receptor that allows the SARS-CoV-2 virus to enter.

“We therefore hypothesize that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19,” wrote Michael Roth, MD, and his associates in their recent article (Lancet Resp Med. 2020 Mar 11. doi: 10.1016/S2213-2600[20]30116-8). While the potential clinical impact of an increase in the number of ACE2 molecules in a cell’s surface membrane remains uninvestigated, the risk this phenomenon poses should mean that patients taking these drugs should receive heightened monitoring for COVID-19 disease, suggested Dr. Roth, a professor of biomedicine who specializes in studying inflammatory lung diseases including asthma, and associates.

However, others who have considered the impact that ACE inhibitors and ARBs might have on ACE2 and COVID-19 infections have noted that the picture is not simple. “Higher ACE2 expression following chronically medicating SARS‐CoV‐2 infected patients with AT1R [angiotensin receptor 1] blockers, while seemingly paradoxical, may protect them against acute lung injury rather than putting them at higher risk to develop SARS. This may be accounted for by two complementary mechanisms: blocking the excessive angiotensin‐mediated AT1R activation caused by the viral infection, as well as up-regulating ACE2, thereby reducing angiotensin production by ACE and increasing the production” of a vasodilating form of angiotensin, wrote David Gurwitz, PhD, in a recently published editorial (Drug Dev Res. 2020 Mar 4. doi: 10.1002/ddr.21656). A data-mining approach may allow researchers to determine whether patients who received drugs that interfere with angiotensin 1 function prior to being diagnosed with a COVID-19 infection had a better disease outcome, suggested Dr. Gurwitz, a molecular geneticist at Tel Aviv University in Jerusalem.

The statement from the three U.S. cardiology societies came a few days following a similar statement of support for ongoing use of ACE inhibitors and ARBs from the European Society of Cardiology’s Council on Hypertension.

Dr. Harrington, Dr. Kovacs, Dr. Roth, and Dr. Gurwitz had no relevant disclosures.

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Controversy continued over the potential effect of drugs that interfere with the renin-angiotensin-aldosterone system via the angiotensin-converting enzymes (ACE) may have on exacerbating infection with the SARS-CoV-2 virus that causes COVID-19.

A joint statement from the American Heart Association, American College of Cardiology, and the Heart Failure Society of America on March 17 gave full, unqualified support to maintaining patients on drugs that work this way, specifically the ACE inhibitors and angiotensin-receptor blockers (ARBs), which together form a long-standing cornerstone of treatment for hypertension, heart failure, and ischemic heart disease.

The three societies “recommend continuation” of ACE inhibitors or ARBs “for all patients already prescribed.” The statement went on to say that patients already diagnosed with a COVID-19 infection “should be fully evaluated before adding or removing any treatments, and any changes to their treatment should be based on the latest scientific evidence and shared decision making with their physician and health care team.”

“We understand the concern – as it has become clear that people with cardiovascular disease are at much higher risk of serious complications including death from COVID-19. However, we have reviewed the latest research – the evidence does not confirm the need to discontinue ACE inhibitors or ARBs, and we strongly recommend all physicians to consider the individual needs of each patient before making any changes to ACE-inhibitor or ARB treatment regimens,” said Robert A. Harrington, MD, president of the American Heart Association and professor and chair of medicine at Stanford (Calif.) University, in the statement.

“There are no experimental or clinical data demonstrating beneficial or adverse outcomes among COVID-19 patients using ACE-inhibitor or ARB medications,” added Richard J. Kovacs, MD, president of the American College of Cardiology and professor of cardiology at Indiana University in Indianapolis.



The “latest research” referred to in the statement likely focuses on a report that had appeared less than a week earlier in a British journal that hypothesized a possible increase in the susceptibility of human epithelial cells of the lungs, intestine, kidneys, and blood vessels exposed to these or certain other drugs, like the thiazolidinedione oral diabetes drugs or ibuprofen, because they cause up-regulation of the ACE2 protein in cell membranes, and ACE2 is the primary cell-surface receptor that allows the SARS-CoV-2 virus to enter.

“We therefore hypothesize that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19,” wrote Michael Roth, MD, and his associates in their recent article (Lancet Resp Med. 2020 Mar 11. doi: 10.1016/S2213-2600[20]30116-8). While the potential clinical impact of an increase in the number of ACE2 molecules in a cell’s surface membrane remains uninvestigated, the risk this phenomenon poses should mean that patients taking these drugs should receive heightened monitoring for COVID-19 disease, suggested Dr. Roth, a professor of biomedicine who specializes in studying inflammatory lung diseases including asthma, and associates.

However, others who have considered the impact that ACE inhibitors and ARBs might have on ACE2 and COVID-19 infections have noted that the picture is not simple. “Higher ACE2 expression following chronically medicating SARS‐CoV‐2 infected patients with AT1R [angiotensin receptor 1] blockers, while seemingly paradoxical, may protect them against acute lung injury rather than putting them at higher risk to develop SARS. This may be accounted for by two complementary mechanisms: blocking the excessive angiotensin‐mediated AT1R activation caused by the viral infection, as well as up-regulating ACE2, thereby reducing angiotensin production by ACE and increasing the production” of a vasodilating form of angiotensin, wrote David Gurwitz, PhD, in a recently published editorial (Drug Dev Res. 2020 Mar 4. doi: 10.1002/ddr.21656). A data-mining approach may allow researchers to determine whether patients who received drugs that interfere with angiotensin 1 function prior to being diagnosed with a COVID-19 infection had a better disease outcome, suggested Dr. Gurwitz, a molecular geneticist at Tel Aviv University in Jerusalem.

The statement from the three U.S. cardiology societies came a few days following a similar statement of support for ongoing use of ACE inhibitors and ARBs from the European Society of Cardiology’s Council on Hypertension.

Dr. Harrington, Dr. Kovacs, Dr. Roth, and Dr. Gurwitz had no relevant disclosures.

Controversy continued over the potential effect of drugs that interfere with the renin-angiotensin-aldosterone system via the angiotensin-converting enzymes (ACE) may have on exacerbating infection with the SARS-CoV-2 virus that causes COVID-19.

A joint statement from the American Heart Association, American College of Cardiology, and the Heart Failure Society of America on March 17 gave full, unqualified support to maintaining patients on drugs that work this way, specifically the ACE inhibitors and angiotensin-receptor blockers (ARBs), which together form a long-standing cornerstone of treatment for hypertension, heart failure, and ischemic heart disease.

The three societies “recommend continuation” of ACE inhibitors or ARBs “for all patients already prescribed.” The statement went on to say that patients already diagnosed with a COVID-19 infection “should be fully evaluated before adding or removing any treatments, and any changes to their treatment should be based on the latest scientific evidence and shared decision making with their physician and health care team.”

“We understand the concern – as it has become clear that people with cardiovascular disease are at much higher risk of serious complications including death from COVID-19. However, we have reviewed the latest research – the evidence does not confirm the need to discontinue ACE inhibitors or ARBs, and we strongly recommend all physicians to consider the individual needs of each patient before making any changes to ACE-inhibitor or ARB treatment regimens,” said Robert A. Harrington, MD, president of the American Heart Association and professor and chair of medicine at Stanford (Calif.) University, in the statement.

“There are no experimental or clinical data demonstrating beneficial or adverse outcomes among COVID-19 patients using ACE-inhibitor or ARB medications,” added Richard J. Kovacs, MD, president of the American College of Cardiology and professor of cardiology at Indiana University in Indianapolis.



The “latest research” referred to in the statement likely focuses on a report that had appeared less than a week earlier in a British journal that hypothesized a possible increase in the susceptibility of human epithelial cells of the lungs, intestine, kidneys, and blood vessels exposed to these or certain other drugs, like the thiazolidinedione oral diabetes drugs or ibuprofen, because they cause up-regulation of the ACE2 protein in cell membranes, and ACE2 is the primary cell-surface receptor that allows the SARS-CoV-2 virus to enter.

“We therefore hypothesize that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19,” wrote Michael Roth, MD, and his associates in their recent article (Lancet Resp Med. 2020 Mar 11. doi: 10.1016/S2213-2600[20]30116-8). While the potential clinical impact of an increase in the number of ACE2 molecules in a cell’s surface membrane remains uninvestigated, the risk this phenomenon poses should mean that patients taking these drugs should receive heightened monitoring for COVID-19 disease, suggested Dr. Roth, a professor of biomedicine who specializes in studying inflammatory lung diseases including asthma, and associates.

However, others who have considered the impact that ACE inhibitors and ARBs might have on ACE2 and COVID-19 infections have noted that the picture is not simple. “Higher ACE2 expression following chronically medicating SARS‐CoV‐2 infected patients with AT1R [angiotensin receptor 1] blockers, while seemingly paradoxical, may protect them against acute lung injury rather than putting them at higher risk to develop SARS. This may be accounted for by two complementary mechanisms: blocking the excessive angiotensin‐mediated AT1R activation caused by the viral infection, as well as up-regulating ACE2, thereby reducing angiotensin production by ACE and increasing the production” of a vasodilating form of angiotensin, wrote David Gurwitz, PhD, in a recently published editorial (Drug Dev Res. 2020 Mar 4. doi: 10.1002/ddr.21656). A data-mining approach may allow researchers to determine whether patients who received drugs that interfere with angiotensin 1 function prior to being diagnosed with a COVID-19 infection had a better disease outcome, suggested Dr. Gurwitz, a molecular geneticist at Tel Aviv University in Jerusalem.

The statement from the three U.S. cardiology societies came a few days following a similar statement of support for ongoing use of ACE inhibitors and ARBs from the European Society of Cardiology’s Council on Hypertension.

Dr. Harrington, Dr. Kovacs, Dr. Roth, and Dr. Gurwitz had no relevant disclosures.

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