User login
Eat more dairy, less red meat to prevent type 2 diabetes
STOCKHOLM – Among animal protein foods, low-fat dairy consumption may minimize the risk of developing type 2 diabetes while red meat raises that risk, a new analysis finds.
“A plant-based dietary pattern with limited intake of meat, moderate intake of fish, eggs, and full-fat dairy, and habitual consumption of yogurt, milk, or low-fat dairy, might represent the most feasible, sustainable, and successful population strategy to optimize the prevention of type 2 diabetes,” lead author Annalisa Giosuè, MD, of the University of Naples (Italy) Federico II, told this news organization.
She presented the findings from an umbrella review of 13 dose-response meta-analyses of prospective cohort studies at the annual meeting of the European Association for the Study of Diabetes.
The study is believed to be the first comprehensive overview of the available evidence from all published meta-analyses on the relationship between well-defined amounts of animal-origin foods and the risk of type 2 diabetes.
Dr. Giosuè and colleagues focused on animal-based foods because they represent a gap in most guidelines for type 2 diabetes prevention, she explained.
“The existing evidence and dietary recommendations for type 2 diabetes prevention are mainly based on the appropriate consumption of plant foods: high amounts of the fiber-rich ones and low consumption of the refined ones as well as those rich in free sugars. And also on the adequate choice among fat sources – reduction of saturated fat sources like butter and cream and replacement with plant-based poly- and monounsaturated fat sources like nontropical vegetable oils. But not on the most suitable choices among different animal foods for the prevention of type 2 diabetes,” she explained.
The new findings are in line with the Mediterranean diet in that, while plant based, it also limits red-meat consumption, but not all animal-based foods, and has consistently been associated with a reduced risk of type 2 diabetes. Vegetarian diets have also been associated with a reduced risk of type 2 diabetes, but far less evidence is available for that, she said.
Asked for comment, session moderator Matthias Schulze, MD, head of the department of molecular epidemiology at the German Institute of Human Nutrition, Berlin, said: “Decreasing intake of red and processed meat is already a strong recommendation, and these data support that. You have to make choices for and against [certain] foods. So, if you decide to eat less red meat, then the question is what do you eat instead? This study shows that specifically other animal products, like dairy and ... fish or white meat sources ... are healthy among the animal-based foods. But you could also obviously look at plant-based foods as protein sources as well.”
And Dr. Schulze noted that the data suggest another dimension to type 2 diabetes prevention beyond simply focusing on weight loss.
“You can achieve weight loss with very different diets. Diet quality plays an important role. These data support that if you look at diabetes prevention, then you would focus on people with high intakes of specific animal-based foods, besides looking at overweight and obesity. Then you could intervene to reduce this intake, with potential substitutions with other animal foods like fish or white meat, or plant-based sources of proteins.”
Red meat damages, dairy protects
The 13 meta-analyses included 175 summary risk ratios for type 2 diabetes incidence for the consumption of total meat, red meat, white meat, processed meats, fish, total dairy, full-fat dairy, low-fat dairy, milk, cheese, yogurt, or eggs.
Significant increases in the risk of developing type 2 diabetes were found for consumption of 100 g/day of total meat (SRR, 1.20; 20% increase) and red meat (SRR, 1.22, 22% increase) and with 50 g/day of processed meats (SRR, 1.30; 30% increase). A borderline increased risk was also seen for 50 g/day of white meat (SRR, 1.04; 4% increase).
The opposite was found for dairy foods. Inverse associations for type 2 diabetes development were found for an intake of 200 g/day of total dairy (SRR, 0.95; 5% reduction), low-fat dairy (SRR, 0.96; 4% reduction), milk (SRR, 0.90; 10% reduction), and for 100 g/day of yogurt (SRR, 0.94, 6% reduction).
Neutral (nonsignificant) effects were found for 200 g/day of full-fat dairy (SRR, 0.98) and for 30 g/day of cheese (SRR, 0.97). Fish consumption also had a neutral association with type 2 diabetes risk (SRR, 1.04 for 100 g/day) as did one egg per day (SRR, 1.07), but evidence quality was low.
And, Dr. Giosuè noted during her presentation, these relationships could change with alterations in the amounts consumed.
Dr. Schulze commented: “Fish is more clearly related to reduced cardiovascular risk than for preventing type 2 diabetes, where we’ve had mixed results. They might not always be the same.”
What are the mechanisms?
The reasons for these positive and negative associations aren’t entirely clear, but Dr. Giosuè noted that dairy products contain several nutrients, vitamins, and other components, such as calcium and vitamin D, that have potential beneficial effects on glucose metabolism.
In particular, she said, “Whey proteins in milk have a well-known beneficial effect on the regulation of the rise of glucose levels in the blood after meals, and also on the control of appetite and body weight.”
Moreover, probiotics found in yogurt have been linked to protective effects against weight gain and obesity, which “may in part [explain] the beneficial role of yogurt in type 2 diabetes prevention.”
Meat, in contrast, is full of cholesterol, saturated fatty acids, and heme iron, which can promote subclinical inflammation and oxidative stress, which may in turn, affect insulin sensitivity, Dr. Giosuè explained. What’s more, “processed meats also contain nitrates, nitrites, and sodium that can contribute to pancreatic cell damage and vascular dysfunction, thus affecting insulin sensitivity.”
And white meat (poultry) has a lower fat content than red meats such as beef, lamb, and pork, as well as a more favorable fatty acid profile and a lower heme-iron content, she said in an interview.
What about vegan diets? The devil is in the details
Asked about the relative health benefits of diets that completely eliminate animal-based foods, Dr. Giosuè replied: “What is important to keep in mind when hearing about the potential of vegan diets to prevent, or manage, or induce the remission of type 2 diabetes, is that the inclusion in the diet of solely foods of plant origin does not mean ‘automatically’ to eat only foods that are good for diabetes prevention.”
“Just like the exclusion of all foods of animal origin is not equivalent to reduce the risk of type 2 diabetes ... Solid evidence has demonstrated that plant foods which are refined and/or rich in free sugars like white bread, biscuits, and sweetened beverages are as harmful as red and processed meats for diabetes incidence and progression.”
Dr. Giosuè and Dr. Schulze have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
STOCKHOLM – Among animal protein foods, low-fat dairy consumption may minimize the risk of developing type 2 diabetes while red meat raises that risk, a new analysis finds.
“A plant-based dietary pattern with limited intake of meat, moderate intake of fish, eggs, and full-fat dairy, and habitual consumption of yogurt, milk, or low-fat dairy, might represent the most feasible, sustainable, and successful population strategy to optimize the prevention of type 2 diabetes,” lead author Annalisa Giosuè, MD, of the University of Naples (Italy) Federico II, told this news organization.
She presented the findings from an umbrella review of 13 dose-response meta-analyses of prospective cohort studies at the annual meeting of the European Association for the Study of Diabetes.
The study is believed to be the first comprehensive overview of the available evidence from all published meta-analyses on the relationship between well-defined amounts of animal-origin foods and the risk of type 2 diabetes.
Dr. Giosuè and colleagues focused on animal-based foods because they represent a gap in most guidelines for type 2 diabetes prevention, she explained.
“The existing evidence and dietary recommendations for type 2 diabetes prevention are mainly based on the appropriate consumption of plant foods: high amounts of the fiber-rich ones and low consumption of the refined ones as well as those rich in free sugars. And also on the adequate choice among fat sources – reduction of saturated fat sources like butter and cream and replacement with plant-based poly- and monounsaturated fat sources like nontropical vegetable oils. But not on the most suitable choices among different animal foods for the prevention of type 2 diabetes,” she explained.
The new findings are in line with the Mediterranean diet in that, while plant based, it also limits red-meat consumption, but not all animal-based foods, and has consistently been associated with a reduced risk of type 2 diabetes. Vegetarian diets have also been associated with a reduced risk of type 2 diabetes, but far less evidence is available for that, she said.
Asked for comment, session moderator Matthias Schulze, MD, head of the department of molecular epidemiology at the German Institute of Human Nutrition, Berlin, said: “Decreasing intake of red and processed meat is already a strong recommendation, and these data support that. You have to make choices for and against [certain] foods. So, if you decide to eat less red meat, then the question is what do you eat instead? This study shows that specifically other animal products, like dairy and ... fish or white meat sources ... are healthy among the animal-based foods. But you could also obviously look at plant-based foods as protein sources as well.”
And Dr. Schulze noted that the data suggest another dimension to type 2 diabetes prevention beyond simply focusing on weight loss.
“You can achieve weight loss with very different diets. Diet quality plays an important role. These data support that if you look at diabetes prevention, then you would focus on people with high intakes of specific animal-based foods, besides looking at overweight and obesity. Then you could intervene to reduce this intake, with potential substitutions with other animal foods like fish or white meat, or plant-based sources of proteins.”
Red meat damages, dairy protects
The 13 meta-analyses included 175 summary risk ratios for type 2 diabetes incidence for the consumption of total meat, red meat, white meat, processed meats, fish, total dairy, full-fat dairy, low-fat dairy, milk, cheese, yogurt, or eggs.
Significant increases in the risk of developing type 2 diabetes were found for consumption of 100 g/day of total meat (SRR, 1.20; 20% increase) and red meat (SRR, 1.22, 22% increase) and with 50 g/day of processed meats (SRR, 1.30; 30% increase). A borderline increased risk was also seen for 50 g/day of white meat (SRR, 1.04; 4% increase).
The opposite was found for dairy foods. Inverse associations for type 2 diabetes development were found for an intake of 200 g/day of total dairy (SRR, 0.95; 5% reduction), low-fat dairy (SRR, 0.96; 4% reduction), milk (SRR, 0.90; 10% reduction), and for 100 g/day of yogurt (SRR, 0.94, 6% reduction).
Neutral (nonsignificant) effects were found for 200 g/day of full-fat dairy (SRR, 0.98) and for 30 g/day of cheese (SRR, 0.97). Fish consumption also had a neutral association with type 2 diabetes risk (SRR, 1.04 for 100 g/day) as did one egg per day (SRR, 1.07), but evidence quality was low.
And, Dr. Giosuè noted during her presentation, these relationships could change with alterations in the amounts consumed.
Dr. Schulze commented: “Fish is more clearly related to reduced cardiovascular risk than for preventing type 2 diabetes, where we’ve had mixed results. They might not always be the same.”
What are the mechanisms?
The reasons for these positive and negative associations aren’t entirely clear, but Dr. Giosuè noted that dairy products contain several nutrients, vitamins, and other components, such as calcium and vitamin D, that have potential beneficial effects on glucose metabolism.
In particular, she said, “Whey proteins in milk have a well-known beneficial effect on the regulation of the rise of glucose levels in the blood after meals, and also on the control of appetite and body weight.”
Moreover, probiotics found in yogurt have been linked to protective effects against weight gain and obesity, which “may in part [explain] the beneficial role of yogurt in type 2 diabetes prevention.”
Meat, in contrast, is full of cholesterol, saturated fatty acids, and heme iron, which can promote subclinical inflammation and oxidative stress, which may in turn, affect insulin sensitivity, Dr. Giosuè explained. What’s more, “processed meats also contain nitrates, nitrites, and sodium that can contribute to pancreatic cell damage and vascular dysfunction, thus affecting insulin sensitivity.”
And white meat (poultry) has a lower fat content than red meats such as beef, lamb, and pork, as well as a more favorable fatty acid profile and a lower heme-iron content, she said in an interview.
What about vegan diets? The devil is in the details
Asked about the relative health benefits of diets that completely eliminate animal-based foods, Dr. Giosuè replied: “What is important to keep in mind when hearing about the potential of vegan diets to prevent, or manage, or induce the remission of type 2 diabetes, is that the inclusion in the diet of solely foods of plant origin does not mean ‘automatically’ to eat only foods that are good for diabetes prevention.”
“Just like the exclusion of all foods of animal origin is not equivalent to reduce the risk of type 2 diabetes ... Solid evidence has demonstrated that plant foods which are refined and/or rich in free sugars like white bread, biscuits, and sweetened beverages are as harmful as red and processed meats for diabetes incidence and progression.”
Dr. Giosuè and Dr. Schulze have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
STOCKHOLM – Among animal protein foods, low-fat dairy consumption may minimize the risk of developing type 2 diabetes while red meat raises that risk, a new analysis finds.
“A plant-based dietary pattern with limited intake of meat, moderate intake of fish, eggs, and full-fat dairy, and habitual consumption of yogurt, milk, or low-fat dairy, might represent the most feasible, sustainable, and successful population strategy to optimize the prevention of type 2 diabetes,” lead author Annalisa Giosuè, MD, of the University of Naples (Italy) Federico II, told this news organization.
She presented the findings from an umbrella review of 13 dose-response meta-analyses of prospective cohort studies at the annual meeting of the European Association for the Study of Diabetes.
The study is believed to be the first comprehensive overview of the available evidence from all published meta-analyses on the relationship between well-defined amounts of animal-origin foods and the risk of type 2 diabetes.
Dr. Giosuè and colleagues focused on animal-based foods because they represent a gap in most guidelines for type 2 diabetes prevention, she explained.
“The existing evidence and dietary recommendations for type 2 diabetes prevention are mainly based on the appropriate consumption of plant foods: high amounts of the fiber-rich ones and low consumption of the refined ones as well as those rich in free sugars. And also on the adequate choice among fat sources – reduction of saturated fat sources like butter and cream and replacement with plant-based poly- and monounsaturated fat sources like nontropical vegetable oils. But not on the most suitable choices among different animal foods for the prevention of type 2 diabetes,” she explained.
The new findings are in line with the Mediterranean diet in that, while plant based, it also limits red-meat consumption, but not all animal-based foods, and has consistently been associated with a reduced risk of type 2 diabetes. Vegetarian diets have also been associated with a reduced risk of type 2 diabetes, but far less evidence is available for that, she said.
Asked for comment, session moderator Matthias Schulze, MD, head of the department of molecular epidemiology at the German Institute of Human Nutrition, Berlin, said: “Decreasing intake of red and processed meat is already a strong recommendation, and these data support that. You have to make choices for and against [certain] foods. So, if you decide to eat less red meat, then the question is what do you eat instead? This study shows that specifically other animal products, like dairy and ... fish or white meat sources ... are healthy among the animal-based foods. But you could also obviously look at plant-based foods as protein sources as well.”
And Dr. Schulze noted that the data suggest another dimension to type 2 diabetes prevention beyond simply focusing on weight loss.
“You can achieve weight loss with very different diets. Diet quality plays an important role. These data support that if you look at diabetes prevention, then you would focus on people with high intakes of specific animal-based foods, besides looking at overweight and obesity. Then you could intervene to reduce this intake, with potential substitutions with other animal foods like fish or white meat, or plant-based sources of proteins.”
Red meat damages, dairy protects
The 13 meta-analyses included 175 summary risk ratios for type 2 diabetes incidence for the consumption of total meat, red meat, white meat, processed meats, fish, total dairy, full-fat dairy, low-fat dairy, milk, cheese, yogurt, or eggs.
Significant increases in the risk of developing type 2 diabetes were found for consumption of 100 g/day of total meat (SRR, 1.20; 20% increase) and red meat (SRR, 1.22, 22% increase) and with 50 g/day of processed meats (SRR, 1.30; 30% increase). A borderline increased risk was also seen for 50 g/day of white meat (SRR, 1.04; 4% increase).
The opposite was found for dairy foods. Inverse associations for type 2 diabetes development were found for an intake of 200 g/day of total dairy (SRR, 0.95; 5% reduction), low-fat dairy (SRR, 0.96; 4% reduction), milk (SRR, 0.90; 10% reduction), and for 100 g/day of yogurt (SRR, 0.94, 6% reduction).
Neutral (nonsignificant) effects were found for 200 g/day of full-fat dairy (SRR, 0.98) and for 30 g/day of cheese (SRR, 0.97). Fish consumption also had a neutral association with type 2 diabetes risk (SRR, 1.04 for 100 g/day) as did one egg per day (SRR, 1.07), but evidence quality was low.
And, Dr. Giosuè noted during her presentation, these relationships could change with alterations in the amounts consumed.
Dr. Schulze commented: “Fish is more clearly related to reduced cardiovascular risk than for preventing type 2 diabetes, where we’ve had mixed results. They might not always be the same.”
What are the mechanisms?
The reasons for these positive and negative associations aren’t entirely clear, but Dr. Giosuè noted that dairy products contain several nutrients, vitamins, and other components, such as calcium and vitamin D, that have potential beneficial effects on glucose metabolism.
In particular, she said, “Whey proteins in milk have a well-known beneficial effect on the regulation of the rise of glucose levels in the blood after meals, and also on the control of appetite and body weight.”
Moreover, probiotics found in yogurt have been linked to protective effects against weight gain and obesity, which “may in part [explain] the beneficial role of yogurt in type 2 diabetes prevention.”
Meat, in contrast, is full of cholesterol, saturated fatty acids, and heme iron, which can promote subclinical inflammation and oxidative stress, which may in turn, affect insulin sensitivity, Dr. Giosuè explained. What’s more, “processed meats also contain nitrates, nitrites, and sodium that can contribute to pancreatic cell damage and vascular dysfunction, thus affecting insulin sensitivity.”
And white meat (poultry) has a lower fat content than red meats such as beef, lamb, and pork, as well as a more favorable fatty acid profile and a lower heme-iron content, she said in an interview.
What about vegan diets? The devil is in the details
Asked about the relative health benefits of diets that completely eliminate animal-based foods, Dr. Giosuè replied: “What is important to keep in mind when hearing about the potential of vegan diets to prevent, or manage, or induce the remission of type 2 diabetes, is that the inclusion in the diet of solely foods of plant origin does not mean ‘automatically’ to eat only foods that are good for diabetes prevention.”
“Just like the exclusion of all foods of animal origin is not equivalent to reduce the risk of type 2 diabetes ... Solid evidence has demonstrated that plant foods which are refined and/or rich in free sugars like white bread, biscuits, and sweetened beverages are as harmful as red and processed meats for diabetes incidence and progression.”
Dr. Giosuè and Dr. Schulze have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT EASD 2022
PASCAL for MV repair noninferior to MitraClip in CLASP IID; FDA took notice
A newly available transcatheter device for edge-to-edge mitral valve (MV) repair, named for a famed scientist-inventor, is similar to the long-available MitraClip (Abbott) for short-term efficacy and safety, suggests an interim but prespecified analysis from a randomized trial.
In its comparison with MitraClip, the PASCAL transcatheter valve repair system (Edwards Lifesciences) was noninferior with respect to 30-day major adverse events and to success at achieving mitral regurgitation (MR) of no more than moderate severity within 6 months. The trial had entered patients with significant, symptomatic degenerative MR considered too high-risk for surgical repair or replacement.
The interim analysis covers 180 of the 300 patients followed in the study, of whom 117 received the PASCAL device and 63 were given MitraClip. Both groups showed significant gains in functional class, symptom status, and quality of life over 6 months, reported D. Scott Lim, MD, University of Virginia Health System Hospital, Charlottesville, and Konstantinos Koulogiannis, MD, Morristown Medical Center, N.J., jointly on Sept. 17 at the Transcatheter Cardiovascular Therapeutics (TCT) 2022 annual meeting in Boston.
Dr. Lim, one of the trial’s principal investigators, is also lead author on its same-day publication in JACC: Cardiovascular Interventions.
Based largely on those results from the CLASP IID pivotal trial, the U.S. Food and Drug Administration recently approved the PASCAL system for use in patients with degenerative MR, Edwards announced on Sept. 15. The device was approved in the European Union on Aug. 17.
MitraClip has been available in various iterations in the United States since 2013 and in Europe since 2008.
“It’s good for the field to be able to say we have two devices that are comparable,” giving clinicians more options, Vinod H. Thourani, MD, Piedmont Heart Institute, Atlanta, told this news organization.
The current analysis shows that “we’ve yet to figure out what patient pathologies will be beneficial” for each of the devices, Dr. Thourani said. “The goal will be to find out if there are certain anatomical considerations where one device is better than the other.”
It will be necessary to study “more patients, a larger cohort, with longer follow-up to allow us to see their true benefits,” he said, as well as to conduct more subgroup analyses. For now, the choice of device will probably be “operator-specific, which they feel comfortable with.”
Dr. Thourani, not an author on the current study, is the U.S. principal investigator for the CLASP IIF study looking at clinical outcomes with the two devices and says he consults for both Edwards and Abbott.
The findings are “preliminary for now,” said Michael Young, MD, Dartmouth-Hitchcock Medical Center, Lebanon, N.H., in part because, like most randomized trials, CLASP IID entered a select, not broadly representative population.
“They want to make, as best as they could, an apples-to-apples comparison, without confounding that might make it more difficult to interpret it afterwards,” Dr. Young, not associated with the trial, told this news organization.
But CLASP IID “did enroll patients that we do see and treat, so undoubtedly it’s a compelling study. We now have another device that is shown to be safe and effective. How we’re going to extrapolate it to all the patients that are being referred to our practices will, I think, be under debate and deliberation.”
The PASCAL and MitraClip devices each may be more suitable for different patients with varying mitral valve pathologies because of differences in their designs, Dr. Lim said. The PASCAL’s relative flexibility might make it preferable in patients with smaller mitral valves, and its ability to elongate during delivery could make it more suitable for patients with chordal-dense areas around the valve, he speculated.
MitraClip, Dr. Lim told this news organization, has a mechanical closure system for anchoring that may make it more appropriate for “more complicated, thicker leaflets with calcium.”
CLASP IID enrolled patients with grade 3+ or 4+ degenerative MR considered to be “at prohibitive surgical risk” at 43 sites in North America and Europe. It randomly assigned them 2-to-1 to receive the PASCAL device or MitraClip.
Either of two PASCAL versions were used, the original device or the “smaller, narrower” PASCAL Ace, Dr. Lim observed. Both versions are covered by the PASCAL Precision System FDA approval. About 40% of patients assigned to MitraClip received older versions of the device and about 60%, more recent versions, as they were entered into practice.
The mean procedure times were 88 minutes for PASCAL and 79 minutes for MitraClip (P = .023), with much of the difference attributable to the earliest PASCAL procedures. Procedure times for the device declined with greater operator experience, the published report states.
Rates of the primary safety endpoint of major adverse events at 30 days were 3.4% for PASCAL and 4.8% for MitraClip. The endpoint was a composite of cardiovascular mortality, stroke, myocardial infarction, new need for renal replacement therapy, severe bleeding, or nonelective MV reintervention.
The proportion of patients with MR grade 2+ or lower at 6 months, the primary effectiveness endpoint, assessed at a core laboratory, was 96.5% for the PASCAL group over a median follow-up of 179.5 days and 96.8% over a median of 184.5 days for those who received MitraClip.
Comparisons for both primary endpoints met the prespecified criteria for PASCAL noninferiority.
In a secondary analysis, the proportion of PASCAL patients with MR grade 1+ or less held about steady from postprocedure discharge out to 6 months, at 87.2% and 83.7%, respectively (P = .317).
But whereas 88.5% of MitraClip patients had MR grade 1+ or better at discharge, 71.2% were at that grade by 6 months (P = .003). That apparent hemodynamic deterioration raised some eyebrows at the TCT sessions as a potential sign that PASCAL functional results are more durable.
That sort of judgment is premature, offered Anita W. Asgar, MD, MSc, Montreal Heart Institute, Quebec City, as an invited discussant after the CLASP IID trial’s formal presentation at the meeting, which was sponsored by the Cardiovascular Research Foundation.
The trial is notable in part for “showing how safe this procedure is and how successful it is for these patients – this is phenomenal,” she said, but “I would caution comparing one device being better than another with such a small number of patients.”
MitraClip, Dr. Young observed, “has been, up to this point, our only option for edge-to-edge repair of the mitral valve. And many of us have years of experience and a lot of patients that we treat with that device.” His center hasn’t yet used PASCAL, but that may change as the field gains more familiarity with the device. Operators may use either device in different cases, he said.
“Depending on the program, and depending on the volume of mitral patients that you see and edge-to-edge repair that you do, it could be that you stick with one, or switch to another, or you integrate both of them and try to decide which patients might be better suited for one or the other.”
CLASP IID was sponsored by Edwards Lifesciences. Dr. Lim discloses consulting for Philips, Venus, and Valgen and receiving research grants from Abbott, Boston Scientific, Edwards Lifesciences, and Medtronic. Dr. Koulogiannis discloses consulting and serving on an advisory board for Edwards Lifesciences and as a speaker for Abbott and discloses holding equity, stocks, or stock options in 4C. Dr. Thourani discloses serving as a consultant to both Abbott and Edwards Lifesciences. Dr. Young discloses receiving consulting fees or honoraria or serving on a speaker’s bureau for Medtronic. Dr. Asgar discloses receiving research support from or holding a research contract with Abbott Vascular and receiving consulting fees or honoraria or serving on a speaker’s bureau for Medtronic, Edwards Lifesciences, and W. Gore & Associates.
A version of this article first appeared on Medscape.com.
A newly available transcatheter device for edge-to-edge mitral valve (MV) repair, named for a famed scientist-inventor, is similar to the long-available MitraClip (Abbott) for short-term efficacy and safety, suggests an interim but prespecified analysis from a randomized trial.
In its comparison with MitraClip, the PASCAL transcatheter valve repair system (Edwards Lifesciences) was noninferior with respect to 30-day major adverse events and to success at achieving mitral regurgitation (MR) of no more than moderate severity within 6 months. The trial had entered patients with significant, symptomatic degenerative MR considered too high-risk for surgical repair or replacement.
The interim analysis covers 180 of the 300 patients followed in the study, of whom 117 received the PASCAL device and 63 were given MitraClip. Both groups showed significant gains in functional class, symptom status, and quality of life over 6 months, reported D. Scott Lim, MD, University of Virginia Health System Hospital, Charlottesville, and Konstantinos Koulogiannis, MD, Morristown Medical Center, N.J., jointly on Sept. 17 at the Transcatheter Cardiovascular Therapeutics (TCT) 2022 annual meeting in Boston.
Dr. Lim, one of the trial’s principal investigators, is also lead author on its same-day publication in JACC: Cardiovascular Interventions.
Based largely on those results from the CLASP IID pivotal trial, the U.S. Food and Drug Administration recently approved the PASCAL system for use in patients with degenerative MR, Edwards announced on Sept. 15. The device was approved in the European Union on Aug. 17.
MitraClip has been available in various iterations in the United States since 2013 and in Europe since 2008.
“It’s good for the field to be able to say we have two devices that are comparable,” giving clinicians more options, Vinod H. Thourani, MD, Piedmont Heart Institute, Atlanta, told this news organization.
The current analysis shows that “we’ve yet to figure out what patient pathologies will be beneficial” for each of the devices, Dr. Thourani said. “The goal will be to find out if there are certain anatomical considerations where one device is better than the other.”
It will be necessary to study “more patients, a larger cohort, with longer follow-up to allow us to see their true benefits,” he said, as well as to conduct more subgroup analyses. For now, the choice of device will probably be “operator-specific, which they feel comfortable with.”
Dr. Thourani, not an author on the current study, is the U.S. principal investigator for the CLASP IIF study looking at clinical outcomes with the two devices and says he consults for both Edwards and Abbott.
The findings are “preliminary for now,” said Michael Young, MD, Dartmouth-Hitchcock Medical Center, Lebanon, N.H., in part because, like most randomized trials, CLASP IID entered a select, not broadly representative population.
“They want to make, as best as they could, an apples-to-apples comparison, without confounding that might make it more difficult to interpret it afterwards,” Dr. Young, not associated with the trial, told this news organization.
But CLASP IID “did enroll patients that we do see and treat, so undoubtedly it’s a compelling study. We now have another device that is shown to be safe and effective. How we’re going to extrapolate it to all the patients that are being referred to our practices will, I think, be under debate and deliberation.”
The PASCAL and MitraClip devices each may be more suitable for different patients with varying mitral valve pathologies because of differences in their designs, Dr. Lim said. The PASCAL’s relative flexibility might make it preferable in patients with smaller mitral valves, and its ability to elongate during delivery could make it more suitable for patients with chordal-dense areas around the valve, he speculated.
MitraClip, Dr. Lim told this news organization, has a mechanical closure system for anchoring that may make it more appropriate for “more complicated, thicker leaflets with calcium.”
CLASP IID enrolled patients with grade 3+ or 4+ degenerative MR considered to be “at prohibitive surgical risk” at 43 sites in North America and Europe. It randomly assigned them 2-to-1 to receive the PASCAL device or MitraClip.
Either of two PASCAL versions were used, the original device or the “smaller, narrower” PASCAL Ace, Dr. Lim observed. Both versions are covered by the PASCAL Precision System FDA approval. About 40% of patients assigned to MitraClip received older versions of the device and about 60%, more recent versions, as they were entered into practice.
The mean procedure times were 88 minutes for PASCAL and 79 minutes for MitraClip (P = .023), with much of the difference attributable to the earliest PASCAL procedures. Procedure times for the device declined with greater operator experience, the published report states.
Rates of the primary safety endpoint of major adverse events at 30 days were 3.4% for PASCAL and 4.8% for MitraClip. The endpoint was a composite of cardiovascular mortality, stroke, myocardial infarction, new need for renal replacement therapy, severe bleeding, or nonelective MV reintervention.
The proportion of patients with MR grade 2+ or lower at 6 months, the primary effectiveness endpoint, assessed at a core laboratory, was 96.5% for the PASCAL group over a median follow-up of 179.5 days and 96.8% over a median of 184.5 days for those who received MitraClip.
Comparisons for both primary endpoints met the prespecified criteria for PASCAL noninferiority.
In a secondary analysis, the proportion of PASCAL patients with MR grade 1+ or less held about steady from postprocedure discharge out to 6 months, at 87.2% and 83.7%, respectively (P = .317).
But whereas 88.5% of MitraClip patients had MR grade 1+ or better at discharge, 71.2% were at that grade by 6 months (P = .003). That apparent hemodynamic deterioration raised some eyebrows at the TCT sessions as a potential sign that PASCAL functional results are more durable.
That sort of judgment is premature, offered Anita W. Asgar, MD, MSc, Montreal Heart Institute, Quebec City, as an invited discussant after the CLASP IID trial’s formal presentation at the meeting, which was sponsored by the Cardiovascular Research Foundation.
The trial is notable in part for “showing how safe this procedure is and how successful it is for these patients – this is phenomenal,” she said, but “I would caution comparing one device being better than another with such a small number of patients.”
MitraClip, Dr. Young observed, “has been, up to this point, our only option for edge-to-edge repair of the mitral valve. And many of us have years of experience and a lot of patients that we treat with that device.” His center hasn’t yet used PASCAL, but that may change as the field gains more familiarity with the device. Operators may use either device in different cases, he said.
“Depending on the program, and depending on the volume of mitral patients that you see and edge-to-edge repair that you do, it could be that you stick with one, or switch to another, or you integrate both of them and try to decide which patients might be better suited for one or the other.”
CLASP IID was sponsored by Edwards Lifesciences. Dr. Lim discloses consulting for Philips, Venus, and Valgen and receiving research grants from Abbott, Boston Scientific, Edwards Lifesciences, and Medtronic. Dr. Koulogiannis discloses consulting and serving on an advisory board for Edwards Lifesciences and as a speaker for Abbott and discloses holding equity, stocks, or stock options in 4C. Dr. Thourani discloses serving as a consultant to both Abbott and Edwards Lifesciences. Dr. Young discloses receiving consulting fees or honoraria or serving on a speaker’s bureau for Medtronic. Dr. Asgar discloses receiving research support from or holding a research contract with Abbott Vascular and receiving consulting fees or honoraria or serving on a speaker’s bureau for Medtronic, Edwards Lifesciences, and W. Gore & Associates.
A version of this article first appeared on Medscape.com.
A newly available transcatheter device for edge-to-edge mitral valve (MV) repair, named for a famed scientist-inventor, is similar to the long-available MitraClip (Abbott) for short-term efficacy and safety, suggests an interim but prespecified analysis from a randomized trial.
In its comparison with MitraClip, the PASCAL transcatheter valve repair system (Edwards Lifesciences) was noninferior with respect to 30-day major adverse events and to success at achieving mitral regurgitation (MR) of no more than moderate severity within 6 months. The trial had entered patients with significant, symptomatic degenerative MR considered too high-risk for surgical repair or replacement.
The interim analysis covers 180 of the 300 patients followed in the study, of whom 117 received the PASCAL device and 63 were given MitraClip. Both groups showed significant gains in functional class, symptom status, and quality of life over 6 months, reported D. Scott Lim, MD, University of Virginia Health System Hospital, Charlottesville, and Konstantinos Koulogiannis, MD, Morristown Medical Center, N.J., jointly on Sept. 17 at the Transcatheter Cardiovascular Therapeutics (TCT) 2022 annual meeting in Boston.
Dr. Lim, one of the trial’s principal investigators, is also lead author on its same-day publication in JACC: Cardiovascular Interventions.
Based largely on those results from the CLASP IID pivotal trial, the U.S. Food and Drug Administration recently approved the PASCAL system for use in patients with degenerative MR, Edwards announced on Sept. 15. The device was approved in the European Union on Aug. 17.
MitraClip has been available in various iterations in the United States since 2013 and in Europe since 2008.
“It’s good for the field to be able to say we have two devices that are comparable,” giving clinicians more options, Vinod H. Thourani, MD, Piedmont Heart Institute, Atlanta, told this news organization.
The current analysis shows that “we’ve yet to figure out what patient pathologies will be beneficial” for each of the devices, Dr. Thourani said. “The goal will be to find out if there are certain anatomical considerations where one device is better than the other.”
It will be necessary to study “more patients, a larger cohort, with longer follow-up to allow us to see their true benefits,” he said, as well as to conduct more subgroup analyses. For now, the choice of device will probably be “operator-specific, which they feel comfortable with.”
Dr. Thourani, not an author on the current study, is the U.S. principal investigator for the CLASP IIF study looking at clinical outcomes with the two devices and says he consults for both Edwards and Abbott.
The findings are “preliminary for now,” said Michael Young, MD, Dartmouth-Hitchcock Medical Center, Lebanon, N.H., in part because, like most randomized trials, CLASP IID entered a select, not broadly representative population.
“They want to make, as best as they could, an apples-to-apples comparison, without confounding that might make it more difficult to interpret it afterwards,” Dr. Young, not associated with the trial, told this news organization.
But CLASP IID “did enroll patients that we do see and treat, so undoubtedly it’s a compelling study. We now have another device that is shown to be safe and effective. How we’re going to extrapolate it to all the patients that are being referred to our practices will, I think, be under debate and deliberation.”
The PASCAL and MitraClip devices each may be more suitable for different patients with varying mitral valve pathologies because of differences in their designs, Dr. Lim said. The PASCAL’s relative flexibility might make it preferable in patients with smaller mitral valves, and its ability to elongate during delivery could make it more suitable for patients with chordal-dense areas around the valve, he speculated.
MitraClip, Dr. Lim told this news organization, has a mechanical closure system for anchoring that may make it more appropriate for “more complicated, thicker leaflets with calcium.”
CLASP IID enrolled patients with grade 3+ or 4+ degenerative MR considered to be “at prohibitive surgical risk” at 43 sites in North America and Europe. It randomly assigned them 2-to-1 to receive the PASCAL device or MitraClip.
Either of two PASCAL versions were used, the original device or the “smaller, narrower” PASCAL Ace, Dr. Lim observed. Both versions are covered by the PASCAL Precision System FDA approval. About 40% of patients assigned to MitraClip received older versions of the device and about 60%, more recent versions, as they were entered into practice.
The mean procedure times were 88 minutes for PASCAL and 79 minutes for MitraClip (P = .023), with much of the difference attributable to the earliest PASCAL procedures. Procedure times for the device declined with greater operator experience, the published report states.
Rates of the primary safety endpoint of major adverse events at 30 days were 3.4% for PASCAL and 4.8% for MitraClip. The endpoint was a composite of cardiovascular mortality, stroke, myocardial infarction, new need for renal replacement therapy, severe bleeding, or nonelective MV reintervention.
The proportion of patients with MR grade 2+ or lower at 6 months, the primary effectiveness endpoint, assessed at a core laboratory, was 96.5% for the PASCAL group over a median follow-up of 179.5 days and 96.8% over a median of 184.5 days for those who received MitraClip.
Comparisons for both primary endpoints met the prespecified criteria for PASCAL noninferiority.
In a secondary analysis, the proportion of PASCAL patients with MR grade 1+ or less held about steady from postprocedure discharge out to 6 months, at 87.2% and 83.7%, respectively (P = .317).
But whereas 88.5% of MitraClip patients had MR grade 1+ or better at discharge, 71.2% were at that grade by 6 months (P = .003). That apparent hemodynamic deterioration raised some eyebrows at the TCT sessions as a potential sign that PASCAL functional results are more durable.
That sort of judgment is premature, offered Anita W. Asgar, MD, MSc, Montreal Heart Institute, Quebec City, as an invited discussant after the CLASP IID trial’s formal presentation at the meeting, which was sponsored by the Cardiovascular Research Foundation.
The trial is notable in part for “showing how safe this procedure is and how successful it is for these patients – this is phenomenal,” she said, but “I would caution comparing one device being better than another with such a small number of patients.”
MitraClip, Dr. Young observed, “has been, up to this point, our only option for edge-to-edge repair of the mitral valve. And many of us have years of experience and a lot of patients that we treat with that device.” His center hasn’t yet used PASCAL, but that may change as the field gains more familiarity with the device. Operators may use either device in different cases, he said.
“Depending on the program, and depending on the volume of mitral patients that you see and edge-to-edge repair that you do, it could be that you stick with one, or switch to another, or you integrate both of them and try to decide which patients might be better suited for one or the other.”
CLASP IID was sponsored by Edwards Lifesciences. Dr. Lim discloses consulting for Philips, Venus, and Valgen and receiving research grants from Abbott, Boston Scientific, Edwards Lifesciences, and Medtronic. Dr. Koulogiannis discloses consulting and serving on an advisory board for Edwards Lifesciences and as a speaker for Abbott and discloses holding equity, stocks, or stock options in 4C. Dr. Thourani discloses serving as a consultant to both Abbott and Edwards Lifesciences. Dr. Young discloses receiving consulting fees or honoraria or serving on a speaker’s bureau for Medtronic. Dr. Asgar discloses receiving research support from or holding a research contract with Abbott Vascular and receiving consulting fees or honoraria or serving on a speaker’s bureau for Medtronic, Edwards Lifesciences, and W. Gore & Associates.
A version of this article first appeared on Medscape.com.
FROM TCT 2022
Waist-hip ratio beats BMI for predicting obesity’s mortality risk
STOCKHOLM – New evidence continues to show that alternative measures of adiposity than body mass index, such as waist-to-hip ratio, work better for predicting the risk a person with overweight or obesity faces from their excess weight.
A direct comparison of waist-to-hip ratio (WHR), body mass index (BMI), and fat mass index (FMI) in a total of more than 380,000 United Kingdom residents included in the UK Biobank showed that WHR had the strongest and most consistent relationship to all-cause death, compared with the other two measures, indicating that clinicians should pay more attention to adiposity distribution than they do to BMI when prioritizing obesity interventions, Irfan Khan said at the annual meeting of the European Association for the Study of Diabetes.
Although it’s likely “way too early” to fully replace BMI as a measure of adiposity, because it is so established in guidelines and in practice, it is now time to “use WHR as an adjunct to BMI” suggested Mr. Khan in an interview.
“A lot of work still needs to be done to translate WHR into practice, but I think it’s getting closer,” said Mr. Khan, a medical student at McMaster University, Hamilton, Ont., who performed his analyses in collaboration with a research team based primarily at McMaster.
Moving away from BMI-centric obesity
“This is a timely topic, because guidelines for treating people with obesity have depended so much on BMI. We want to go from a BMI-centric view to a view of obesity that depends more on disease burden,” commented Matthias Blüher, MD, professor of molecular endocrinology and head of the Obesity Outpatient Clinic for Adults at the University of Leipzig (Germany).
For example, the 2016 obesity management guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology called for a “complications-centric” approach to assessing and intervening in people with obesity rather than a “BMI-centric” approach.
But Dr. Blüher went a step further in an interview, adding that “waist-to-hip ratio is now outdated,” with adjusted measures of WHR such as waist-to-height ratio “considered a better proxy for all-cause death.” He also gave high marks to the Edmonton Obesity Staging System, which independently added to BMI as well as to a diagnosis of metabolic syndrome for predicting mortality in a sample from the U.S. National Health and Nutrition Examination Survey (NHANES). The Edmonton System also surpassed BMI for disease-severity staging using data from more than 23,000 Canadians with a BMI that denoted obesity.
1 standard deviation increase in WHR linked with a 41% increased mortality
The study reported by Mr. Khan used both epidemiologic and Mendelian randomization analyses on data collected from more than 380,000 U.K. residents included in the UK Biobank database to examine the statistical associations between BMI, FMI, and WHR and all-cause death. This showed that while BMI and FMI both had significant, independent associations with all-cause mortality, with hazard ratios of 1.14 for each 1 standard deviation increase in BMI and of 1.17 for each standard deviation increase in FMI, the link was a stronger 1.41 per standard deviation increase in WHR, he said.
Another analysis that divided the entire UK Biobank study cohort into 20 roughly similar subgroups by their BMI showed that WHR had the most consistent association across the BMI spectrum.
Further analyses showed that WHR also strongly and significantly linked with cardiovascular disease death and with other causes of death that were not cardiovascular, cancer-related, or associated with respiratory diseases. And the WHR link to all-cause mortality was strongest in men, and much less robust in women, likely because visceral adiposity is much more common among men, even compared with the postmenopausal women who predominate in the UK Biobank cohort.
One more feature of WHR that makes it an attractive metric is its relative ease of measurement, about as easy as BMI, Mr. Khan said.
The study received no commercial funding, and Mr. Khan had no disclosures. Dr. Blüher has been a consultant to or speaker on behalf of Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk, and Sanofi.
STOCKHOLM – New evidence continues to show that alternative measures of adiposity than body mass index, such as waist-to-hip ratio, work better for predicting the risk a person with overweight or obesity faces from their excess weight.
A direct comparison of waist-to-hip ratio (WHR), body mass index (BMI), and fat mass index (FMI) in a total of more than 380,000 United Kingdom residents included in the UK Biobank showed that WHR had the strongest and most consistent relationship to all-cause death, compared with the other two measures, indicating that clinicians should pay more attention to adiposity distribution than they do to BMI when prioritizing obesity interventions, Irfan Khan said at the annual meeting of the European Association for the Study of Diabetes.
Although it’s likely “way too early” to fully replace BMI as a measure of adiposity, because it is so established in guidelines and in practice, it is now time to “use WHR as an adjunct to BMI” suggested Mr. Khan in an interview.
“A lot of work still needs to be done to translate WHR into practice, but I think it’s getting closer,” said Mr. Khan, a medical student at McMaster University, Hamilton, Ont., who performed his analyses in collaboration with a research team based primarily at McMaster.
Moving away from BMI-centric obesity
“This is a timely topic, because guidelines for treating people with obesity have depended so much on BMI. We want to go from a BMI-centric view to a view of obesity that depends more on disease burden,” commented Matthias Blüher, MD, professor of molecular endocrinology and head of the Obesity Outpatient Clinic for Adults at the University of Leipzig (Germany).
For example, the 2016 obesity management guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology called for a “complications-centric” approach to assessing and intervening in people with obesity rather than a “BMI-centric” approach.
But Dr. Blüher went a step further in an interview, adding that “waist-to-hip ratio is now outdated,” with adjusted measures of WHR such as waist-to-height ratio “considered a better proxy for all-cause death.” He also gave high marks to the Edmonton Obesity Staging System, which independently added to BMI as well as to a diagnosis of metabolic syndrome for predicting mortality in a sample from the U.S. National Health and Nutrition Examination Survey (NHANES). The Edmonton System also surpassed BMI for disease-severity staging using data from more than 23,000 Canadians with a BMI that denoted obesity.
1 standard deviation increase in WHR linked with a 41% increased mortality
The study reported by Mr. Khan used both epidemiologic and Mendelian randomization analyses on data collected from more than 380,000 U.K. residents included in the UK Biobank database to examine the statistical associations between BMI, FMI, and WHR and all-cause death. This showed that while BMI and FMI both had significant, independent associations with all-cause mortality, with hazard ratios of 1.14 for each 1 standard deviation increase in BMI and of 1.17 for each standard deviation increase in FMI, the link was a stronger 1.41 per standard deviation increase in WHR, he said.
Another analysis that divided the entire UK Biobank study cohort into 20 roughly similar subgroups by their BMI showed that WHR had the most consistent association across the BMI spectrum.
Further analyses showed that WHR also strongly and significantly linked with cardiovascular disease death and with other causes of death that were not cardiovascular, cancer-related, or associated with respiratory diseases. And the WHR link to all-cause mortality was strongest in men, and much less robust in women, likely because visceral adiposity is much more common among men, even compared with the postmenopausal women who predominate in the UK Biobank cohort.
One more feature of WHR that makes it an attractive metric is its relative ease of measurement, about as easy as BMI, Mr. Khan said.
The study received no commercial funding, and Mr. Khan had no disclosures. Dr. Blüher has been a consultant to or speaker on behalf of Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk, and Sanofi.
STOCKHOLM – New evidence continues to show that alternative measures of adiposity than body mass index, such as waist-to-hip ratio, work better for predicting the risk a person with overweight or obesity faces from their excess weight.
A direct comparison of waist-to-hip ratio (WHR), body mass index (BMI), and fat mass index (FMI) in a total of more than 380,000 United Kingdom residents included in the UK Biobank showed that WHR had the strongest and most consistent relationship to all-cause death, compared with the other two measures, indicating that clinicians should pay more attention to adiposity distribution than they do to BMI when prioritizing obesity interventions, Irfan Khan said at the annual meeting of the European Association for the Study of Diabetes.
Although it’s likely “way too early” to fully replace BMI as a measure of adiposity, because it is so established in guidelines and in practice, it is now time to “use WHR as an adjunct to BMI” suggested Mr. Khan in an interview.
“A lot of work still needs to be done to translate WHR into practice, but I think it’s getting closer,” said Mr. Khan, a medical student at McMaster University, Hamilton, Ont., who performed his analyses in collaboration with a research team based primarily at McMaster.
Moving away from BMI-centric obesity
“This is a timely topic, because guidelines for treating people with obesity have depended so much on BMI. We want to go from a BMI-centric view to a view of obesity that depends more on disease burden,” commented Matthias Blüher, MD, professor of molecular endocrinology and head of the Obesity Outpatient Clinic for Adults at the University of Leipzig (Germany).
For example, the 2016 obesity management guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology called for a “complications-centric” approach to assessing and intervening in people with obesity rather than a “BMI-centric” approach.
But Dr. Blüher went a step further in an interview, adding that “waist-to-hip ratio is now outdated,” with adjusted measures of WHR such as waist-to-height ratio “considered a better proxy for all-cause death.” He also gave high marks to the Edmonton Obesity Staging System, which independently added to BMI as well as to a diagnosis of metabolic syndrome for predicting mortality in a sample from the U.S. National Health and Nutrition Examination Survey (NHANES). The Edmonton System also surpassed BMI for disease-severity staging using data from more than 23,000 Canadians with a BMI that denoted obesity.
1 standard deviation increase in WHR linked with a 41% increased mortality
The study reported by Mr. Khan used both epidemiologic and Mendelian randomization analyses on data collected from more than 380,000 U.K. residents included in the UK Biobank database to examine the statistical associations between BMI, FMI, and WHR and all-cause death. This showed that while BMI and FMI both had significant, independent associations with all-cause mortality, with hazard ratios of 1.14 for each 1 standard deviation increase in BMI and of 1.17 for each standard deviation increase in FMI, the link was a stronger 1.41 per standard deviation increase in WHR, he said.
Another analysis that divided the entire UK Biobank study cohort into 20 roughly similar subgroups by their BMI showed that WHR had the most consistent association across the BMI spectrum.
Further analyses showed that WHR also strongly and significantly linked with cardiovascular disease death and with other causes of death that were not cardiovascular, cancer-related, or associated with respiratory diseases. And the WHR link to all-cause mortality was strongest in men, and much less robust in women, likely because visceral adiposity is much more common among men, even compared with the postmenopausal women who predominate in the UK Biobank cohort.
One more feature of WHR that makes it an attractive metric is its relative ease of measurement, about as easy as BMI, Mr. Khan said.
The study received no commercial funding, and Mr. Khan had no disclosures. Dr. Blüher has been a consultant to or speaker on behalf of Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk, and Sanofi.
AT EASD 2022
A week of anticoagulation halves post-PCI radial occlusion rate
Serious bleeding is not increased
BOSTON – Following transradial access for angiography or a percutaneous coronary intervention (PCI), a low dose of the factor Xa inhibitor rivaroxaban for 7 days reduces the risk of an access-site occlusion by 50%, according to results of the randomized RIVARAD trial.
Of two multicenter, randomized trials to address this question it is the larger, according to Rania Hammami, MD, who presented the results at the Transcatheter Cardiovascular Therapeutics annual meeting.
In the open-label RIVARAD trial, 538 patients were randomized to 10 mg rivaroxaban or standard care alone. Standard care at the beginning of the procedure included unfractionated heparin in a dose of 50 IU/kg for angiography and up to 100 IU/kg for PCI. Manual compression was applied at the end of the procedure followed by an evaluation for complications, such as hematoma or aneurysm.
For the primary outcome of radial access occlusion at 30 days, the lower rate in the rivaroxaban arm (6.9% vs. 13.0%) translated into a statistically significant 50% reduction (odds ratio, 0.50; P = .011).
Rivaroxaban preserves radial pulse
Rivaroxaban was also favored for the endpoint of inability at 30 days to find a radial pulse (5.8% vs. 12.2%; P = .01). Interestingly, there was some disparity for this endpoint for clinical examination and ultrasound.
“In 12 patients, we were able to palpate a radial pulse, but the ultrasound showed an occlusion of the vessel, while in 7 patients we could not find a radial pulse even though the radial artery was patent on ultrasound,” Dr. Hammami, of the department of cardiology, Hedi Chaker Hospital, Sfax, Tunisia, said at the meeting, sponsored by the Cardiovascular Research Foundation.
The incidence of hemorrhagic complications was higher in the rivaroxaban group (2.7% vs. 1.9%), but the difference did not approach statistical significance (OR, 1.5; P = .54). Moreover, all of the bleeding complications were minor (Bleeding Academic Research Consortium level 1), and none of the bleeding complications were observed in patients receiving rivaroxaban alone. Rather, all patients with bleeding were taking one or more antiplatelet drugs along with rivaroxaban.
On univariate analysis, several baseline characteristics were associated with subsequent radial occlusion, including female sex (P = .02), current smoking (P = .03), renal failure (P = .004), and PCI for acute coronary syndrome (P = .02). On multivariate analysis, female sex (P = .001) and current smoking (P < .0001) became even stronger predictors of occlusion on a statistical basis, while a prior procedure involving radial access was also a significant predictor (P = .029).
“One woman out of two developed radial access occlusion if she had a history of smoking and had a history of a transradial puncture,” Dr. Hammami reported.
In a subgroup analysis, relative protection from radial artery occlusion from a 7-day course of rivaroxaban was particularly pronounced in those with diabetes, renal failure, or hypertension relative to those without these conditions, but the protective effect appeared to be about the same regardless of body mass index, age, sheath size, or current use of statins.
These findings are consistent with other studies evaluating the risk of radial access occlusion, according to Dr. Hammami. While different studies she cited reported incidences ranging from less than 1% to more than 30%, the risk has typically been highest in populations with increased susceptibility for thrombus formation, such as smokers and patients with diabetes.
Preventing radial artery occlusion has several benefits, not least of which is preserving this access point for future interventions, according to Dr. Hammami.
RIVARAD is the largest study to evaluate an anticoagulant for the prevention of radial artery occlusion, but it is not the first. Earlier in 2022, a Chinese trial called RESTORE was published in Circulation: Cardiovascular Interventions. In that placebo-controlled study of 382 patients, 7 days of 10 mg rivaroxaban was also linked to a significant reduction in radial artery occlusion at 30 days (3.8% vs. 11.5%; P = .011).
“We don’t know if a higher dose of rivaroxaban would be more effective and equally safe,” said Dr. Hammami, but added that a Canadian trial called CAPITAL RAPTOR will test this premise. In this trial, there is a planned enrollment of 1,800 patients who will be randomized to 15 mg rivaroxaban or standard treatment.
Occlusion risk appears underappreciated
The risk of radial artery occlusion might be underappreciated. According to data cited by Dr. Hammami, only about half of interventionalists in the United States and fewer than 10% outside of the United States routinely assess radial artery patency in conjunction with radial-access PCI. The data from this trial suggest that the risk can be substantially reduced, particularly in high-risk patients, with anticoagulant therapy.
Agreeing that this is a potentially avoidable complication, Roxanna Mehran, MD, director of interventional cardiovascular research and clinical trials, Icahn School of Medicine at Mount Sinai, New York, called the RIVARAD study “a clinically meaningful trial,” and valuable for identifying risk factors as well as for showing a treatment effect and acceptable safety from a short course of a factor Xa inhibitor.
“This is very important work,” said Dr. Mehran, who praised the quality of the study and the contribution it makes for considering how and when prophylaxis is needed.
Dr. Hammami reported no potential conflicts of interest. Dr. Mehran has financial relationships with more than 25 pharmaceutical companies but none with the sponsor of this trial, which was funded by Philadelphia Pharma, a drug company based in Tunisia.
Serious bleeding is not increased
Serious bleeding is not increased
BOSTON – Following transradial access for angiography or a percutaneous coronary intervention (PCI), a low dose of the factor Xa inhibitor rivaroxaban for 7 days reduces the risk of an access-site occlusion by 50%, according to results of the randomized RIVARAD trial.
Of two multicenter, randomized trials to address this question it is the larger, according to Rania Hammami, MD, who presented the results at the Transcatheter Cardiovascular Therapeutics annual meeting.
In the open-label RIVARAD trial, 538 patients were randomized to 10 mg rivaroxaban or standard care alone. Standard care at the beginning of the procedure included unfractionated heparin in a dose of 50 IU/kg for angiography and up to 100 IU/kg for PCI. Manual compression was applied at the end of the procedure followed by an evaluation for complications, such as hematoma or aneurysm.
For the primary outcome of radial access occlusion at 30 days, the lower rate in the rivaroxaban arm (6.9% vs. 13.0%) translated into a statistically significant 50% reduction (odds ratio, 0.50; P = .011).
Rivaroxaban preserves radial pulse
Rivaroxaban was also favored for the endpoint of inability at 30 days to find a radial pulse (5.8% vs. 12.2%; P = .01). Interestingly, there was some disparity for this endpoint for clinical examination and ultrasound.
“In 12 patients, we were able to palpate a radial pulse, but the ultrasound showed an occlusion of the vessel, while in 7 patients we could not find a radial pulse even though the radial artery was patent on ultrasound,” Dr. Hammami, of the department of cardiology, Hedi Chaker Hospital, Sfax, Tunisia, said at the meeting, sponsored by the Cardiovascular Research Foundation.
The incidence of hemorrhagic complications was higher in the rivaroxaban group (2.7% vs. 1.9%), but the difference did not approach statistical significance (OR, 1.5; P = .54). Moreover, all of the bleeding complications were minor (Bleeding Academic Research Consortium level 1), and none of the bleeding complications were observed in patients receiving rivaroxaban alone. Rather, all patients with bleeding were taking one or more antiplatelet drugs along with rivaroxaban.
On univariate analysis, several baseline characteristics were associated with subsequent radial occlusion, including female sex (P = .02), current smoking (P = .03), renal failure (P = .004), and PCI for acute coronary syndrome (P = .02). On multivariate analysis, female sex (P = .001) and current smoking (P < .0001) became even stronger predictors of occlusion on a statistical basis, while a prior procedure involving radial access was also a significant predictor (P = .029).
“One woman out of two developed radial access occlusion if she had a history of smoking and had a history of a transradial puncture,” Dr. Hammami reported.
In a subgroup analysis, relative protection from radial artery occlusion from a 7-day course of rivaroxaban was particularly pronounced in those with diabetes, renal failure, or hypertension relative to those without these conditions, but the protective effect appeared to be about the same regardless of body mass index, age, sheath size, or current use of statins.
These findings are consistent with other studies evaluating the risk of radial access occlusion, according to Dr. Hammami. While different studies she cited reported incidences ranging from less than 1% to more than 30%, the risk has typically been highest in populations with increased susceptibility for thrombus formation, such as smokers and patients with diabetes.
Preventing radial artery occlusion has several benefits, not least of which is preserving this access point for future interventions, according to Dr. Hammami.
RIVARAD is the largest study to evaluate an anticoagulant for the prevention of radial artery occlusion, but it is not the first. Earlier in 2022, a Chinese trial called RESTORE was published in Circulation: Cardiovascular Interventions. In that placebo-controlled study of 382 patients, 7 days of 10 mg rivaroxaban was also linked to a significant reduction in radial artery occlusion at 30 days (3.8% vs. 11.5%; P = .011).
“We don’t know if a higher dose of rivaroxaban would be more effective and equally safe,” said Dr. Hammami, but added that a Canadian trial called CAPITAL RAPTOR will test this premise. In this trial, there is a planned enrollment of 1,800 patients who will be randomized to 15 mg rivaroxaban or standard treatment.
Occlusion risk appears underappreciated
The risk of radial artery occlusion might be underappreciated. According to data cited by Dr. Hammami, only about half of interventionalists in the United States and fewer than 10% outside of the United States routinely assess radial artery patency in conjunction with radial-access PCI. The data from this trial suggest that the risk can be substantially reduced, particularly in high-risk patients, with anticoagulant therapy.
Agreeing that this is a potentially avoidable complication, Roxanna Mehran, MD, director of interventional cardiovascular research and clinical trials, Icahn School of Medicine at Mount Sinai, New York, called the RIVARAD study “a clinically meaningful trial,” and valuable for identifying risk factors as well as for showing a treatment effect and acceptable safety from a short course of a factor Xa inhibitor.
“This is very important work,” said Dr. Mehran, who praised the quality of the study and the contribution it makes for considering how and when prophylaxis is needed.
Dr. Hammami reported no potential conflicts of interest. Dr. Mehran has financial relationships with more than 25 pharmaceutical companies but none with the sponsor of this trial, which was funded by Philadelphia Pharma, a drug company based in Tunisia.
BOSTON – Following transradial access for angiography or a percutaneous coronary intervention (PCI), a low dose of the factor Xa inhibitor rivaroxaban for 7 days reduces the risk of an access-site occlusion by 50%, according to results of the randomized RIVARAD trial.
Of two multicenter, randomized trials to address this question it is the larger, according to Rania Hammami, MD, who presented the results at the Transcatheter Cardiovascular Therapeutics annual meeting.
In the open-label RIVARAD trial, 538 patients were randomized to 10 mg rivaroxaban or standard care alone. Standard care at the beginning of the procedure included unfractionated heparin in a dose of 50 IU/kg for angiography and up to 100 IU/kg for PCI. Manual compression was applied at the end of the procedure followed by an evaluation for complications, such as hematoma or aneurysm.
For the primary outcome of radial access occlusion at 30 days, the lower rate in the rivaroxaban arm (6.9% vs. 13.0%) translated into a statistically significant 50% reduction (odds ratio, 0.50; P = .011).
Rivaroxaban preserves radial pulse
Rivaroxaban was also favored for the endpoint of inability at 30 days to find a radial pulse (5.8% vs. 12.2%; P = .01). Interestingly, there was some disparity for this endpoint for clinical examination and ultrasound.
“In 12 patients, we were able to palpate a radial pulse, but the ultrasound showed an occlusion of the vessel, while in 7 patients we could not find a radial pulse even though the radial artery was patent on ultrasound,” Dr. Hammami, of the department of cardiology, Hedi Chaker Hospital, Sfax, Tunisia, said at the meeting, sponsored by the Cardiovascular Research Foundation.
The incidence of hemorrhagic complications was higher in the rivaroxaban group (2.7% vs. 1.9%), but the difference did not approach statistical significance (OR, 1.5; P = .54). Moreover, all of the bleeding complications were minor (Bleeding Academic Research Consortium level 1), and none of the bleeding complications were observed in patients receiving rivaroxaban alone. Rather, all patients with bleeding were taking one or more antiplatelet drugs along with rivaroxaban.
On univariate analysis, several baseline characteristics were associated with subsequent radial occlusion, including female sex (P = .02), current smoking (P = .03), renal failure (P = .004), and PCI for acute coronary syndrome (P = .02). On multivariate analysis, female sex (P = .001) and current smoking (P < .0001) became even stronger predictors of occlusion on a statistical basis, while a prior procedure involving radial access was also a significant predictor (P = .029).
“One woman out of two developed radial access occlusion if she had a history of smoking and had a history of a transradial puncture,” Dr. Hammami reported.
In a subgroup analysis, relative protection from radial artery occlusion from a 7-day course of rivaroxaban was particularly pronounced in those with diabetes, renal failure, or hypertension relative to those without these conditions, but the protective effect appeared to be about the same regardless of body mass index, age, sheath size, or current use of statins.
These findings are consistent with other studies evaluating the risk of radial access occlusion, according to Dr. Hammami. While different studies she cited reported incidences ranging from less than 1% to more than 30%, the risk has typically been highest in populations with increased susceptibility for thrombus formation, such as smokers and patients with diabetes.
Preventing radial artery occlusion has several benefits, not least of which is preserving this access point for future interventions, according to Dr. Hammami.
RIVARAD is the largest study to evaluate an anticoagulant for the prevention of radial artery occlusion, but it is not the first. Earlier in 2022, a Chinese trial called RESTORE was published in Circulation: Cardiovascular Interventions. In that placebo-controlled study of 382 patients, 7 days of 10 mg rivaroxaban was also linked to a significant reduction in radial artery occlusion at 30 days (3.8% vs. 11.5%; P = .011).
“We don’t know if a higher dose of rivaroxaban would be more effective and equally safe,” said Dr. Hammami, but added that a Canadian trial called CAPITAL RAPTOR will test this premise. In this trial, there is a planned enrollment of 1,800 patients who will be randomized to 15 mg rivaroxaban or standard treatment.
Occlusion risk appears underappreciated
The risk of radial artery occlusion might be underappreciated. According to data cited by Dr. Hammami, only about half of interventionalists in the United States and fewer than 10% outside of the United States routinely assess radial artery patency in conjunction with radial-access PCI. The data from this trial suggest that the risk can be substantially reduced, particularly in high-risk patients, with anticoagulant therapy.
Agreeing that this is a potentially avoidable complication, Roxanna Mehran, MD, director of interventional cardiovascular research and clinical trials, Icahn School of Medicine at Mount Sinai, New York, called the RIVARAD study “a clinically meaningful trial,” and valuable for identifying risk factors as well as for showing a treatment effect and acceptable safety from a short course of a factor Xa inhibitor.
“This is very important work,” said Dr. Mehran, who praised the quality of the study and the contribution it makes for considering how and when prophylaxis is needed.
Dr. Hammami reported no potential conflicts of interest. Dr. Mehran has financial relationships with more than 25 pharmaceutical companies but none with the sponsor of this trial, which was funded by Philadelphia Pharma, a drug company based in Tunisia.
AT TCT 2022
Is acetaminophen really safer than NSAIDs in heart disease?
New research calls into question the assumption that acetaminophen is safer than NSAIDs for patients with known cardiovascular disease (CVD) or CVD risk factors.
The analysis found a significant correlation between the use of acetaminophen and elevated systolic blood pressure.
While acetaminophen may still be safer than NSAIDs from a bleeding risk standpoint, or in patients with known kidney disease, “the gap may not be as large as once thought,” Rahul Gupta, MD, cardiologist with Lehigh Valley Health Network, Allentown, Pa., said in an interview.
“Cautious use is recommended over the long term, especially in patients with pre-existing hypertension or cardiovascular risk factors,” Dr. Gupta said.
The study was presented at the Hypertension Scientific Sessions, San Diego, sponsored by the American Heart Association.
Acetaminophen is one of the most widely used over-the-counter medications, as it is considered a safer medication for long-term use since it lacks the anti-inflammatory effects of NSAIDs, Dr. Gupta explained.
NSAIDs have been known to raise blood pressure, but the effect of acetaminophen in this regard has not been well studied. Observational studies have shown contradictory results in terms of its effect on blood pressure, he noted.
To investigate further, Dr. Gupta and colleagues did a meta-analysis of three studies that compared the effect of acetaminophen (3-4 g/day) versus placebo on systolic and diastolic ambulatory blood pressure in patients with heart disease or hypertension. Together, the studies included 172 adults (mean age, 60 years; 73% male).
They found that patients receiving acetaminophen had significantly higher systolic blood pressure, compared with those receiving placebo (standard mean difference [SMD] = 0.35; 95% confidence interval, 0.08-0.63; P = .01).
Subgroup analysis of the effect on hypertensive patients showed significant change in systolic blood pressure as well (SMD = 0.38; 95% CI, 0.05-0.71; P = .02).
“Interestingly, there was no significant difference in the effect on diastolic blood pressure,” Dr. Gupta commented.
Reached for comment, Timothy S. Anderson, MD, clinical investigator in the Division of General Medicine at Beth Israel Deaconess Medical Center and assistant professor of medicine at the Harvard Medical School, both in Boston, said this is “an interesting and not particularly well-known issue.”
“However, most of the trials look at very high doses of acetaminophen use (for example, six to eight of the 500 mg pills each day) so we don’t really know whether the more common patterns of using one to two acetaminophen pills every once in a while is problematic,” Dr. Anderson told this news organization.
“We also don’t have data showing a direct harm from these medications with regards to strokes or heart attacks or other downstream consequences of high blood pressure. Ideally we would need a head-to-head trial comparing ibuprofen-type medications to acetaminophen-type medications,” Dr. Anderson said.
The study had no specific funding. Dr. Gupta and Dr. Anderson reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
New research calls into question the assumption that acetaminophen is safer than NSAIDs for patients with known cardiovascular disease (CVD) or CVD risk factors.
The analysis found a significant correlation between the use of acetaminophen and elevated systolic blood pressure.
While acetaminophen may still be safer than NSAIDs from a bleeding risk standpoint, or in patients with known kidney disease, “the gap may not be as large as once thought,” Rahul Gupta, MD, cardiologist with Lehigh Valley Health Network, Allentown, Pa., said in an interview.
“Cautious use is recommended over the long term, especially in patients with pre-existing hypertension or cardiovascular risk factors,” Dr. Gupta said.
The study was presented at the Hypertension Scientific Sessions, San Diego, sponsored by the American Heart Association.
Acetaminophen is one of the most widely used over-the-counter medications, as it is considered a safer medication for long-term use since it lacks the anti-inflammatory effects of NSAIDs, Dr. Gupta explained.
NSAIDs have been known to raise blood pressure, but the effect of acetaminophen in this regard has not been well studied. Observational studies have shown contradictory results in terms of its effect on blood pressure, he noted.
To investigate further, Dr. Gupta and colleagues did a meta-analysis of three studies that compared the effect of acetaminophen (3-4 g/day) versus placebo on systolic and diastolic ambulatory blood pressure in patients with heart disease or hypertension. Together, the studies included 172 adults (mean age, 60 years; 73% male).
They found that patients receiving acetaminophen had significantly higher systolic blood pressure, compared with those receiving placebo (standard mean difference [SMD] = 0.35; 95% confidence interval, 0.08-0.63; P = .01).
Subgroup analysis of the effect on hypertensive patients showed significant change in systolic blood pressure as well (SMD = 0.38; 95% CI, 0.05-0.71; P = .02).
“Interestingly, there was no significant difference in the effect on diastolic blood pressure,” Dr. Gupta commented.
Reached for comment, Timothy S. Anderson, MD, clinical investigator in the Division of General Medicine at Beth Israel Deaconess Medical Center and assistant professor of medicine at the Harvard Medical School, both in Boston, said this is “an interesting and not particularly well-known issue.”
“However, most of the trials look at very high doses of acetaminophen use (for example, six to eight of the 500 mg pills each day) so we don’t really know whether the more common patterns of using one to two acetaminophen pills every once in a while is problematic,” Dr. Anderson told this news organization.
“We also don’t have data showing a direct harm from these medications with regards to strokes or heart attacks or other downstream consequences of high blood pressure. Ideally we would need a head-to-head trial comparing ibuprofen-type medications to acetaminophen-type medications,” Dr. Anderson said.
The study had no specific funding. Dr. Gupta and Dr. Anderson reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
New research calls into question the assumption that acetaminophen is safer than NSAIDs for patients with known cardiovascular disease (CVD) or CVD risk factors.
The analysis found a significant correlation between the use of acetaminophen and elevated systolic blood pressure.
While acetaminophen may still be safer than NSAIDs from a bleeding risk standpoint, or in patients with known kidney disease, “the gap may not be as large as once thought,” Rahul Gupta, MD, cardiologist with Lehigh Valley Health Network, Allentown, Pa., said in an interview.
“Cautious use is recommended over the long term, especially in patients with pre-existing hypertension or cardiovascular risk factors,” Dr. Gupta said.
The study was presented at the Hypertension Scientific Sessions, San Diego, sponsored by the American Heart Association.
Acetaminophen is one of the most widely used over-the-counter medications, as it is considered a safer medication for long-term use since it lacks the anti-inflammatory effects of NSAIDs, Dr. Gupta explained.
NSAIDs have been known to raise blood pressure, but the effect of acetaminophen in this regard has not been well studied. Observational studies have shown contradictory results in terms of its effect on blood pressure, he noted.
To investigate further, Dr. Gupta and colleagues did a meta-analysis of three studies that compared the effect of acetaminophen (3-4 g/day) versus placebo on systolic and diastolic ambulatory blood pressure in patients with heart disease or hypertension. Together, the studies included 172 adults (mean age, 60 years; 73% male).
They found that patients receiving acetaminophen had significantly higher systolic blood pressure, compared with those receiving placebo (standard mean difference [SMD] = 0.35; 95% confidence interval, 0.08-0.63; P = .01).
Subgroup analysis of the effect on hypertensive patients showed significant change in systolic blood pressure as well (SMD = 0.38; 95% CI, 0.05-0.71; P = .02).
“Interestingly, there was no significant difference in the effect on diastolic blood pressure,” Dr. Gupta commented.
Reached for comment, Timothy S. Anderson, MD, clinical investigator in the Division of General Medicine at Beth Israel Deaconess Medical Center and assistant professor of medicine at the Harvard Medical School, both in Boston, said this is “an interesting and not particularly well-known issue.”
“However, most of the trials look at very high doses of acetaminophen use (for example, six to eight of the 500 mg pills each day) so we don’t really know whether the more common patterns of using one to two acetaminophen pills every once in a while is problematic,” Dr. Anderson told this news organization.
“We also don’t have data showing a direct harm from these medications with regards to strokes or heart attacks or other downstream consequences of high blood pressure. Ideally we would need a head-to-head trial comparing ibuprofen-type medications to acetaminophen-type medications,” Dr. Anderson said.
The study had no specific funding. Dr. Gupta and Dr. Anderson reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM HYPERTENSION 2022
TAVR now used in almost 50% of younger severe aortic stenosis patients
Among patients with severe isolated aortic stenosis younger than 65, the rate of transcatheter aortic valve replacement (TAVR) now almost matches that of surgical aortic valve replacement (SAVR), despite guideline recommendations to the contrary, a study in a national U.S. population shows.
The 2020 American Heart Association/American College of Cardiology (AHA/ACC) valve guideline recommends SAVR for patients younger than 65 with severe aortic stenosis, the researchers note, but their study showed “near equal utilization between TAVR and SAVR in these younger patients by 2021,” at 48% and 52% respectively.
Toishi Sharma, MD, and colleagues presented these findings in an oral poster session at Transcatheter Cardiovascular Therapeutics 2022, and the study was simultaneously published as a Research Letter in the Journal of the American College of Cardiology (JACC).
“To our knowledge, the current findings represent the first national temporal trends study stratifying [aortic stenosis] therapies according to guideline-recommended age groups: our observations demonstrate the dramatic growth of TAVR in all age groups, including young patients,” the researchers conclude.
They analyzed changes in rates of TAVR and SAVR in a U.S. sample stratified by age: younger than 65 years, 65-80, and older than 80 years.
These findings have implications for lifetime management of younger patients who undergo TAVR, they write, “including issues related to lifetime coronary access, valve durability, and the potential for subsequent TAVR procedures over time.”
Three age groups
In a study published in JACC, this group examined changes in uptake of TAVR versus SAVR in 4,161 patients with aortic stenosis in Vermont, New Hampshire, and Maine, senior author Harold L. Dauerman, MD, said in an interview.
The greatest rate of rise of TAVR was in the group younger than 65, but that study ended in 2019, said Dr. Dauerman, from the University of Vermont Health Network, Burlington.
The 2020 guideline stratifies TAVR and SAVR recommendations such that “less than 65 should primarily be a surgical approach and greater than 80 primarily a TAVR approach, while 65 to 80 is a gray zone, and shared decision-making becomes important,” he noted.
The group hypothesized that recent trials and technology have led to a national increase in TAVR in people younger than 65.
From the Vizient clinical database, including more than 250 U.S. academic centers that perform both TAVR and SAVR, the researchers identified 142,953 patients who underwent TAVR or SAVR for isolated aortic stenosis from Oct. 1, 2015, to Dec. 31, 2021. From 2015 to 2021, the valve replacement rates in the three age groups changed as follows:
- Age less than 65: TAVR rose from 17% to 48%; SAVR fell from 83% to 52%.
- Age 65-80: TAVR rose from 46% to 87%; SAVR fell from 54% to 12%.
- Age greater than 80: TAVR rose from 83% to 99%; SAVR fell from 16% to 1%.
“All ages have grown in the last 7 years in TAVR,” Dr. Dauerman summarized. “The one that’s surprising, and in contradiction to the guideline, is the growth of TAVR in young patients less than 65.”
Among patients younger than 65, prior bypass surgery and congestive heart failure predicted the use of TAVR instead of surgery, whereas bicuspid aortic valve disease was the biggest predictor of surgery instead of TAVR.
Most studies on TAVR valve durability are limited to patients in the randomized trials who were primarily in their mid-70s to mid-80s, some of whom died before a 10-year follow-up, Dr. Dauerman noted.
European guidelines recommend surgery for patients younger than 70, and it would be interesting to see if clinicians there follow this recommendation or if TAVR is now the preferred approach, he added.
There is a need for further, longer study of TAVR in younger patients, he said, to determine whether there are long-term clinical issues of concern.
Strategy depends on more than age
The “findings are not too surprising,” John Carroll, MD, who was not involved in this research, said in an email.
“Age is only one of multiple patient characteristics that enter into consideration of TAVR versus SAVR,” said Dr. Carroll, from Anschutz Medical Campus, University of Colorado, Aurora.
“As the article reports,” he noted, “those less than 65 having TAVR are more likely to have comorbid conditions that likely made the risk of SAVR higher.”
Dr. Carroll was lead author of a review article published in 2020 based on data from the ACC–Society of Thoracic Surgeons (STS)–Transcatheter Valve Therapy (TVT) registry on 276,316 patients who had TAVR in the United States from 2011-2019.
He pointed out that Figure 2 in that review shows that “SAVR is often performed in conjunction with other surgical procedures – another major reason why SAVR remains an important treatment for valvular heart disease.”
“We are awaiting long-term data comparing TAVR to SAVR durability,” Dr. Carroll added, echoing Dr. Dauerman. “So far [there are] no major differences, but it remains a key need to fully understand TAVR and the various models in commercial use.”
“Both TAVR and SAVR used in adults are tissue valves (SAVR with mechanical valves is used in younger patients),” Dr. Carroll noted, “and all tissue valves will eventually fail if the patient lives long enough.”
Patient management strategies need to consider what treatment options exist when the first valve fails. “If the first valve is SAVR, there is now extensive experience with placing a TAVR valve inside a failing SAVR valve, so called Valve-in-Valve or TAVR-in-SAVR. This is the preferred treatment in most patients with failing SAVR valves,” he said.
“On the other hand,” he continued, “we are just beginning to see more and more patients with failing TAVR valves, and the TAVR-in-TAVR procedure is less well understood.”
“Issues such as acute coronary occlusion and long-term difficulty in accessing coronary arteries are being encountered in some patients having TAVR-in-TAVR,” Dr. Carroll noted, which he discusses in a recent editorial he coauthored about the complexities of redo TAVR, published in JACC: Cardiovascular Interventions.
The study received no funding. Dr. Dauerman has research grants and is a consultant for Medtronic and Boston Scientific. Dr. Carroll is a local principal investigator in trials sponsored by Medtronic, Abbott, and Edwards Lifesciences.
A version of this article first appeared on Medscape.com.
Among patients with severe isolated aortic stenosis younger than 65, the rate of transcatheter aortic valve replacement (TAVR) now almost matches that of surgical aortic valve replacement (SAVR), despite guideline recommendations to the contrary, a study in a national U.S. population shows.
The 2020 American Heart Association/American College of Cardiology (AHA/ACC) valve guideline recommends SAVR for patients younger than 65 with severe aortic stenosis, the researchers note, but their study showed “near equal utilization between TAVR and SAVR in these younger patients by 2021,” at 48% and 52% respectively.
Toishi Sharma, MD, and colleagues presented these findings in an oral poster session at Transcatheter Cardiovascular Therapeutics 2022, and the study was simultaneously published as a Research Letter in the Journal of the American College of Cardiology (JACC).
“To our knowledge, the current findings represent the first national temporal trends study stratifying [aortic stenosis] therapies according to guideline-recommended age groups: our observations demonstrate the dramatic growth of TAVR in all age groups, including young patients,” the researchers conclude.
They analyzed changes in rates of TAVR and SAVR in a U.S. sample stratified by age: younger than 65 years, 65-80, and older than 80 years.
These findings have implications for lifetime management of younger patients who undergo TAVR, they write, “including issues related to lifetime coronary access, valve durability, and the potential for subsequent TAVR procedures over time.”
Three age groups
In a study published in JACC, this group examined changes in uptake of TAVR versus SAVR in 4,161 patients with aortic stenosis in Vermont, New Hampshire, and Maine, senior author Harold L. Dauerman, MD, said in an interview.
The greatest rate of rise of TAVR was in the group younger than 65, but that study ended in 2019, said Dr. Dauerman, from the University of Vermont Health Network, Burlington.
The 2020 guideline stratifies TAVR and SAVR recommendations such that “less than 65 should primarily be a surgical approach and greater than 80 primarily a TAVR approach, while 65 to 80 is a gray zone, and shared decision-making becomes important,” he noted.
The group hypothesized that recent trials and technology have led to a national increase in TAVR in people younger than 65.
From the Vizient clinical database, including more than 250 U.S. academic centers that perform both TAVR and SAVR, the researchers identified 142,953 patients who underwent TAVR or SAVR for isolated aortic stenosis from Oct. 1, 2015, to Dec. 31, 2021. From 2015 to 2021, the valve replacement rates in the three age groups changed as follows:
- Age less than 65: TAVR rose from 17% to 48%; SAVR fell from 83% to 52%.
- Age 65-80: TAVR rose from 46% to 87%; SAVR fell from 54% to 12%.
- Age greater than 80: TAVR rose from 83% to 99%; SAVR fell from 16% to 1%.
“All ages have grown in the last 7 years in TAVR,” Dr. Dauerman summarized. “The one that’s surprising, and in contradiction to the guideline, is the growth of TAVR in young patients less than 65.”
Among patients younger than 65, prior bypass surgery and congestive heart failure predicted the use of TAVR instead of surgery, whereas bicuspid aortic valve disease was the biggest predictor of surgery instead of TAVR.
Most studies on TAVR valve durability are limited to patients in the randomized trials who were primarily in their mid-70s to mid-80s, some of whom died before a 10-year follow-up, Dr. Dauerman noted.
European guidelines recommend surgery for patients younger than 70, and it would be interesting to see if clinicians there follow this recommendation or if TAVR is now the preferred approach, he added.
There is a need for further, longer study of TAVR in younger patients, he said, to determine whether there are long-term clinical issues of concern.
Strategy depends on more than age
The “findings are not too surprising,” John Carroll, MD, who was not involved in this research, said in an email.
“Age is only one of multiple patient characteristics that enter into consideration of TAVR versus SAVR,” said Dr. Carroll, from Anschutz Medical Campus, University of Colorado, Aurora.
“As the article reports,” he noted, “those less than 65 having TAVR are more likely to have comorbid conditions that likely made the risk of SAVR higher.”
Dr. Carroll was lead author of a review article published in 2020 based on data from the ACC–Society of Thoracic Surgeons (STS)–Transcatheter Valve Therapy (TVT) registry on 276,316 patients who had TAVR in the United States from 2011-2019.
He pointed out that Figure 2 in that review shows that “SAVR is often performed in conjunction with other surgical procedures – another major reason why SAVR remains an important treatment for valvular heart disease.”
“We are awaiting long-term data comparing TAVR to SAVR durability,” Dr. Carroll added, echoing Dr. Dauerman. “So far [there are] no major differences, but it remains a key need to fully understand TAVR and the various models in commercial use.”
“Both TAVR and SAVR used in adults are tissue valves (SAVR with mechanical valves is used in younger patients),” Dr. Carroll noted, “and all tissue valves will eventually fail if the patient lives long enough.”
Patient management strategies need to consider what treatment options exist when the first valve fails. “If the first valve is SAVR, there is now extensive experience with placing a TAVR valve inside a failing SAVR valve, so called Valve-in-Valve or TAVR-in-SAVR. This is the preferred treatment in most patients with failing SAVR valves,” he said.
“On the other hand,” he continued, “we are just beginning to see more and more patients with failing TAVR valves, and the TAVR-in-TAVR procedure is less well understood.”
“Issues such as acute coronary occlusion and long-term difficulty in accessing coronary arteries are being encountered in some patients having TAVR-in-TAVR,” Dr. Carroll noted, which he discusses in a recent editorial he coauthored about the complexities of redo TAVR, published in JACC: Cardiovascular Interventions.
The study received no funding. Dr. Dauerman has research grants and is a consultant for Medtronic and Boston Scientific. Dr. Carroll is a local principal investigator in trials sponsored by Medtronic, Abbott, and Edwards Lifesciences.
A version of this article first appeared on Medscape.com.
Among patients with severe isolated aortic stenosis younger than 65, the rate of transcatheter aortic valve replacement (TAVR) now almost matches that of surgical aortic valve replacement (SAVR), despite guideline recommendations to the contrary, a study in a national U.S. population shows.
The 2020 American Heart Association/American College of Cardiology (AHA/ACC) valve guideline recommends SAVR for patients younger than 65 with severe aortic stenosis, the researchers note, but their study showed “near equal utilization between TAVR and SAVR in these younger patients by 2021,” at 48% and 52% respectively.
Toishi Sharma, MD, and colleagues presented these findings in an oral poster session at Transcatheter Cardiovascular Therapeutics 2022, and the study was simultaneously published as a Research Letter in the Journal of the American College of Cardiology (JACC).
“To our knowledge, the current findings represent the first national temporal trends study stratifying [aortic stenosis] therapies according to guideline-recommended age groups: our observations demonstrate the dramatic growth of TAVR in all age groups, including young patients,” the researchers conclude.
They analyzed changes in rates of TAVR and SAVR in a U.S. sample stratified by age: younger than 65 years, 65-80, and older than 80 years.
These findings have implications for lifetime management of younger patients who undergo TAVR, they write, “including issues related to lifetime coronary access, valve durability, and the potential for subsequent TAVR procedures over time.”
Three age groups
In a study published in JACC, this group examined changes in uptake of TAVR versus SAVR in 4,161 patients with aortic stenosis in Vermont, New Hampshire, and Maine, senior author Harold L. Dauerman, MD, said in an interview.
The greatest rate of rise of TAVR was in the group younger than 65, but that study ended in 2019, said Dr. Dauerman, from the University of Vermont Health Network, Burlington.
The 2020 guideline stratifies TAVR and SAVR recommendations such that “less than 65 should primarily be a surgical approach and greater than 80 primarily a TAVR approach, while 65 to 80 is a gray zone, and shared decision-making becomes important,” he noted.
The group hypothesized that recent trials and technology have led to a national increase in TAVR in people younger than 65.
From the Vizient clinical database, including more than 250 U.S. academic centers that perform both TAVR and SAVR, the researchers identified 142,953 patients who underwent TAVR or SAVR for isolated aortic stenosis from Oct. 1, 2015, to Dec. 31, 2021. From 2015 to 2021, the valve replacement rates in the three age groups changed as follows:
- Age less than 65: TAVR rose from 17% to 48%; SAVR fell from 83% to 52%.
- Age 65-80: TAVR rose from 46% to 87%; SAVR fell from 54% to 12%.
- Age greater than 80: TAVR rose from 83% to 99%; SAVR fell from 16% to 1%.
“All ages have grown in the last 7 years in TAVR,” Dr. Dauerman summarized. “The one that’s surprising, and in contradiction to the guideline, is the growth of TAVR in young patients less than 65.”
Among patients younger than 65, prior bypass surgery and congestive heart failure predicted the use of TAVR instead of surgery, whereas bicuspid aortic valve disease was the biggest predictor of surgery instead of TAVR.
Most studies on TAVR valve durability are limited to patients in the randomized trials who were primarily in their mid-70s to mid-80s, some of whom died before a 10-year follow-up, Dr. Dauerman noted.
European guidelines recommend surgery for patients younger than 70, and it would be interesting to see if clinicians there follow this recommendation or if TAVR is now the preferred approach, he added.
There is a need for further, longer study of TAVR in younger patients, he said, to determine whether there are long-term clinical issues of concern.
Strategy depends on more than age
The “findings are not too surprising,” John Carroll, MD, who was not involved in this research, said in an email.
“Age is only one of multiple patient characteristics that enter into consideration of TAVR versus SAVR,” said Dr. Carroll, from Anschutz Medical Campus, University of Colorado, Aurora.
“As the article reports,” he noted, “those less than 65 having TAVR are more likely to have comorbid conditions that likely made the risk of SAVR higher.”
Dr. Carroll was lead author of a review article published in 2020 based on data from the ACC–Society of Thoracic Surgeons (STS)–Transcatheter Valve Therapy (TVT) registry on 276,316 patients who had TAVR in the United States from 2011-2019.
He pointed out that Figure 2 in that review shows that “SAVR is often performed in conjunction with other surgical procedures – another major reason why SAVR remains an important treatment for valvular heart disease.”
“We are awaiting long-term data comparing TAVR to SAVR durability,” Dr. Carroll added, echoing Dr. Dauerman. “So far [there are] no major differences, but it remains a key need to fully understand TAVR and the various models in commercial use.”
“Both TAVR and SAVR used in adults are tissue valves (SAVR with mechanical valves is used in younger patients),” Dr. Carroll noted, “and all tissue valves will eventually fail if the patient lives long enough.”
Patient management strategies need to consider what treatment options exist when the first valve fails. “If the first valve is SAVR, there is now extensive experience with placing a TAVR valve inside a failing SAVR valve, so called Valve-in-Valve or TAVR-in-SAVR. This is the preferred treatment in most patients with failing SAVR valves,” he said.
“On the other hand,” he continued, “we are just beginning to see more and more patients with failing TAVR valves, and the TAVR-in-TAVR procedure is less well understood.”
“Issues such as acute coronary occlusion and long-term difficulty in accessing coronary arteries are being encountered in some patients having TAVR-in-TAVR,” Dr. Carroll noted, which he discusses in a recent editorial he coauthored about the complexities of redo TAVR, published in JACC: Cardiovascular Interventions.
The study received no funding. Dr. Dauerman has research grants and is a consultant for Medtronic and Boston Scientific. Dr. Carroll is a local principal investigator in trials sponsored by Medtronic, Abbott, and Edwards Lifesciences.
A version of this article first appeared on Medscape.com.
FROM TCT 2022
In cardiogenic shock, edge-to-edge mitral valve repair improves outcome
In patients with severe mitral regurgitation (MR) and cardiogenic shock, successful transcatheter edge-to-edge repair (TEER) is associated with a substantial reduction in all-cause mortality and lower morbidity at 1 year, according to an analysis of registry data.
The data from this analysis also confirm that “successful reduction of MR is achievable with TEER in most patients with cardiogenic shock,” reported Mohamad A. Alkhouli, MD, an interventional cardiologist and professor of medicine at the Mayo Clinic, Rochester, Minn.
In those with device success, achieved in 85.6% of patients, all-cause mortality was about 21% lower (34.6% vs. 55.5%; P < .001) at 1 year than in those who were not successfully repaired, according to Dr. Alkhouli, who presented the findings at the Transcatheter Cardiovascular Therapeutics annual meeting in Boston. This translated into a reduction in the hazard ratio for death of nearly 50% (hazard ratio, 0.52; 95% confidence interval, 0.43-0.63).
A similar relative benefit was found for the composite endpoint of mortality and heart failure admissions at 1 year. Whether unadjusted (HR, 0.54; 95% CI, 0.45-0.66) or adjusted (HR, 0.51; 95% CI, 0.42-0.62), risk reductions with successful MR reduction, defined as greater than or equal to 1 grade improvement and a final MR grade of less than or equal to 2+, indicated that major adverse outcomes are reduced by about half.
STS/ACC TCT registry data queried
Drawn from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry, 3,797 patients with cardiogenic shock underwent MR repair between November 2013 and December 2021. Outcomes at 1 year were evaluable in 2,773 of these patients. For inclusion, all had to meet at least one of the definitions of cardiogenic shock, such as inotrope use or mechanical circulatory support.
At baseline, 94.5% had a MR severity of at least 3+, and most of these had 4+. Thirty days after treatment, 88.8% had MR severity of 2+ or less, the majority of which had a severity of 1+.
These data address an important question not previously well studied, according to Dr. Alkhouli. In MR patients, cardiogenic shock is associated with a high risk of death, but there has been little evidence that valve repair does not exacerbate, let alone modify, this risk.
These data support the value of intervention, which was performed in almost all patients with MitraClipä (Abbott), the only device available for most of the period in which the registry was queried. However, Dr. Alkhouli cautioned that his data are best considered “hypothesis generating.”
“We need a randomized trial,” he said at the meeting sponsored by the Cardiovascular Research Foundation. He pointed out that this is a complex population for which multiple variables might have skewed results when data are analyzed retrospectively. Not least, those MR patients with cardiogenic shock in the database considered for TEER might well have been relatively healthy and not representative of an unselected population with both MR and cardiogenic shock.
The question might be better answered by the multicenter Canadian trial CAPITAL MINOS, which has just started. Described in an article in the American Heart Journal, it has a planned enrollment of about 150 MR patients with cardiogenic shock randomized to TEER or medical therapy. Results are expected in about 1 year, according to Dr. Alkhouli.
But regarding the present analysis, Dr. Alkhouli did note that sensitivity analyses conducted within his data across risk factors, such as degenerative versus nondegenerative MR, low (< 30%) versus higher left ventricular ejection fraction (LVEF), and presence or absence of an acute coronary syndrome (ACS), consistently supported a benefit from intervention.
Also, cardiogenic shock did not appear to be a factor in device failure, according to Dr. Alkhouli, addressing a potential criticism that cardiogenic shock was an underlying reason for device failure.
More than 90% in NYHA class III or IV heart failure
In this study, the mean age was 73 years. More than 90% were in class III or IV heart failure in the 2 weeks prior to TEER. More than half had established coronary artery disease. Other concomitant cardiovascular morbidities, including atrial fibrillation or flutter (65%), prior MI (39%), and prior stroke or transient ischemic attach (> 10%) were well represented.
When those with device success were compared with those with device failure, the risk profile was comparable. The predicted STS (Society of Thoracic Surgeons) mortality for mitral valve repair among these two groups was 14.8% versus 15% (P = 0.97), respectively.
However, those with device failure did have a lower baseline left ventricular ejection fraction (40.7% vs. 42.9%; P = .009) and a greater prevalence of moderate-to-severe or severe MR (96.1% vs. 84.9%; P < 0.001).
The growing experience with TEER means that benefit has now been shown in several complicated MR groups, such as those with severe ventricular dysfunction, renal insufficiency, and obstructive lung disease. This was a rationale for looking at the impact or repairing MR in patients with cardiogenic shock.
It is a pressing question, according to Dr. Alkhouli. He cited studies suggesting that up to 20% of patients hospitalized for cardiogenic shock have at least moderate-to-severe MR. Conversely, cardiogenic shock is not an uncommon finding in patients with MR.
While Dr. Alkhouli acknowledged that the many variables influencing outcome in patients with MR and cardiogenic shock will make a randomized trial “challenging,” many experts echoed this concern and even expressed some skepticism about the potential for an unbiased trial.
Data confirm MR repair is safe during shock
“These data do show that repair of MR is safe in patients safe in patients with cardiogenic shock,” said Anita W. Asgar, MD, an interventional cardiologist associated with the Montreal Heart Institute. She noted that there was a 5- to 6-day delay among the cardiogenic shock patients prior to undergoing MR repair in this analysis, potentially reflecting an elimination of those at very high risk. Similarly, she suggested that many interventionalists are likely to consider multiple variables before proceeding.
As a result, MR repair may not be amenable to randomization in a cardiogenic shock population, given that this decision is not typically undertaken out of the context of multiple variables.
“I am not sure that a clinical trial is ethical,” she said. She would expect that clinicians enrolling patients would only do so on a selective basis.
Alexandra J. Lansky, MD, Director of the Yale Heart and Vascular Research Program, Yale University, New Haven, Conn., also emphasized the difficulty of controlling for variables, such as the duration of cardiogenic shock, that influence decision-making.
Nevertheless, she called the data “very important” in that they at least lend some objective data for deciding whether to intervene a group of “challenging” patients not uncommonly faced in clinical practice.
Dr. Alkhouli reports financial relationships with Abbott Vascular, Boston Scientific, Johnson & Johnson, and Phillips. Dr. Asgar reports financial relationships with Abbott Vascular, Edwards Lifesciences, W.L. Gore & Associates, and Medtronic. Dr. Lasky reports no potential conflicts of interest.
A version of this article first appeared on Medscape.com.
In patients with severe mitral regurgitation (MR) and cardiogenic shock, successful transcatheter edge-to-edge repair (TEER) is associated with a substantial reduction in all-cause mortality and lower morbidity at 1 year, according to an analysis of registry data.
The data from this analysis also confirm that “successful reduction of MR is achievable with TEER in most patients with cardiogenic shock,” reported Mohamad A. Alkhouli, MD, an interventional cardiologist and professor of medicine at the Mayo Clinic, Rochester, Minn.
In those with device success, achieved in 85.6% of patients, all-cause mortality was about 21% lower (34.6% vs. 55.5%; P < .001) at 1 year than in those who were not successfully repaired, according to Dr. Alkhouli, who presented the findings at the Transcatheter Cardiovascular Therapeutics annual meeting in Boston. This translated into a reduction in the hazard ratio for death of nearly 50% (hazard ratio, 0.52; 95% confidence interval, 0.43-0.63).
A similar relative benefit was found for the composite endpoint of mortality and heart failure admissions at 1 year. Whether unadjusted (HR, 0.54; 95% CI, 0.45-0.66) or adjusted (HR, 0.51; 95% CI, 0.42-0.62), risk reductions with successful MR reduction, defined as greater than or equal to 1 grade improvement and a final MR grade of less than or equal to 2+, indicated that major adverse outcomes are reduced by about half.
STS/ACC TCT registry data queried
Drawn from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry, 3,797 patients with cardiogenic shock underwent MR repair between November 2013 and December 2021. Outcomes at 1 year were evaluable in 2,773 of these patients. For inclusion, all had to meet at least one of the definitions of cardiogenic shock, such as inotrope use or mechanical circulatory support.
At baseline, 94.5% had a MR severity of at least 3+, and most of these had 4+. Thirty days after treatment, 88.8% had MR severity of 2+ or less, the majority of which had a severity of 1+.
These data address an important question not previously well studied, according to Dr. Alkhouli. In MR patients, cardiogenic shock is associated with a high risk of death, but there has been little evidence that valve repair does not exacerbate, let alone modify, this risk.
These data support the value of intervention, which was performed in almost all patients with MitraClipä (Abbott), the only device available for most of the period in which the registry was queried. However, Dr. Alkhouli cautioned that his data are best considered “hypothesis generating.”
“We need a randomized trial,” he said at the meeting sponsored by the Cardiovascular Research Foundation. He pointed out that this is a complex population for which multiple variables might have skewed results when data are analyzed retrospectively. Not least, those MR patients with cardiogenic shock in the database considered for TEER might well have been relatively healthy and not representative of an unselected population with both MR and cardiogenic shock.
The question might be better answered by the multicenter Canadian trial CAPITAL MINOS, which has just started. Described in an article in the American Heart Journal, it has a planned enrollment of about 150 MR patients with cardiogenic shock randomized to TEER or medical therapy. Results are expected in about 1 year, according to Dr. Alkhouli.
But regarding the present analysis, Dr. Alkhouli did note that sensitivity analyses conducted within his data across risk factors, such as degenerative versus nondegenerative MR, low (< 30%) versus higher left ventricular ejection fraction (LVEF), and presence or absence of an acute coronary syndrome (ACS), consistently supported a benefit from intervention.
Also, cardiogenic shock did not appear to be a factor in device failure, according to Dr. Alkhouli, addressing a potential criticism that cardiogenic shock was an underlying reason for device failure.
More than 90% in NYHA class III or IV heart failure
In this study, the mean age was 73 years. More than 90% were in class III or IV heart failure in the 2 weeks prior to TEER. More than half had established coronary artery disease. Other concomitant cardiovascular morbidities, including atrial fibrillation or flutter (65%), prior MI (39%), and prior stroke or transient ischemic attach (> 10%) were well represented.
When those with device success were compared with those with device failure, the risk profile was comparable. The predicted STS (Society of Thoracic Surgeons) mortality for mitral valve repair among these two groups was 14.8% versus 15% (P = 0.97), respectively.
However, those with device failure did have a lower baseline left ventricular ejection fraction (40.7% vs. 42.9%; P = .009) and a greater prevalence of moderate-to-severe or severe MR (96.1% vs. 84.9%; P < 0.001).
The growing experience with TEER means that benefit has now been shown in several complicated MR groups, such as those with severe ventricular dysfunction, renal insufficiency, and obstructive lung disease. This was a rationale for looking at the impact or repairing MR in patients with cardiogenic shock.
It is a pressing question, according to Dr. Alkhouli. He cited studies suggesting that up to 20% of patients hospitalized for cardiogenic shock have at least moderate-to-severe MR. Conversely, cardiogenic shock is not an uncommon finding in patients with MR.
While Dr. Alkhouli acknowledged that the many variables influencing outcome in patients with MR and cardiogenic shock will make a randomized trial “challenging,” many experts echoed this concern and even expressed some skepticism about the potential for an unbiased trial.
Data confirm MR repair is safe during shock
“These data do show that repair of MR is safe in patients safe in patients with cardiogenic shock,” said Anita W. Asgar, MD, an interventional cardiologist associated with the Montreal Heart Institute. She noted that there was a 5- to 6-day delay among the cardiogenic shock patients prior to undergoing MR repair in this analysis, potentially reflecting an elimination of those at very high risk. Similarly, she suggested that many interventionalists are likely to consider multiple variables before proceeding.
As a result, MR repair may not be amenable to randomization in a cardiogenic shock population, given that this decision is not typically undertaken out of the context of multiple variables.
“I am not sure that a clinical trial is ethical,” she said. She would expect that clinicians enrolling patients would only do so on a selective basis.
Alexandra J. Lansky, MD, Director of the Yale Heart and Vascular Research Program, Yale University, New Haven, Conn., also emphasized the difficulty of controlling for variables, such as the duration of cardiogenic shock, that influence decision-making.
Nevertheless, she called the data “very important” in that they at least lend some objective data for deciding whether to intervene a group of “challenging” patients not uncommonly faced in clinical practice.
Dr. Alkhouli reports financial relationships with Abbott Vascular, Boston Scientific, Johnson & Johnson, and Phillips. Dr. Asgar reports financial relationships with Abbott Vascular, Edwards Lifesciences, W.L. Gore & Associates, and Medtronic. Dr. Lasky reports no potential conflicts of interest.
A version of this article first appeared on Medscape.com.
In patients with severe mitral regurgitation (MR) and cardiogenic shock, successful transcatheter edge-to-edge repair (TEER) is associated with a substantial reduction in all-cause mortality and lower morbidity at 1 year, according to an analysis of registry data.
The data from this analysis also confirm that “successful reduction of MR is achievable with TEER in most patients with cardiogenic shock,” reported Mohamad A. Alkhouli, MD, an interventional cardiologist and professor of medicine at the Mayo Clinic, Rochester, Minn.
In those with device success, achieved in 85.6% of patients, all-cause mortality was about 21% lower (34.6% vs. 55.5%; P < .001) at 1 year than in those who were not successfully repaired, according to Dr. Alkhouli, who presented the findings at the Transcatheter Cardiovascular Therapeutics annual meeting in Boston. This translated into a reduction in the hazard ratio for death of nearly 50% (hazard ratio, 0.52; 95% confidence interval, 0.43-0.63).
A similar relative benefit was found for the composite endpoint of mortality and heart failure admissions at 1 year. Whether unadjusted (HR, 0.54; 95% CI, 0.45-0.66) or adjusted (HR, 0.51; 95% CI, 0.42-0.62), risk reductions with successful MR reduction, defined as greater than or equal to 1 grade improvement and a final MR grade of less than or equal to 2+, indicated that major adverse outcomes are reduced by about half.
STS/ACC TCT registry data queried
Drawn from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry, 3,797 patients with cardiogenic shock underwent MR repair between November 2013 and December 2021. Outcomes at 1 year were evaluable in 2,773 of these patients. For inclusion, all had to meet at least one of the definitions of cardiogenic shock, such as inotrope use or mechanical circulatory support.
At baseline, 94.5% had a MR severity of at least 3+, and most of these had 4+. Thirty days after treatment, 88.8% had MR severity of 2+ or less, the majority of which had a severity of 1+.
These data address an important question not previously well studied, according to Dr. Alkhouli. In MR patients, cardiogenic shock is associated with a high risk of death, but there has been little evidence that valve repair does not exacerbate, let alone modify, this risk.
These data support the value of intervention, which was performed in almost all patients with MitraClipä (Abbott), the only device available for most of the period in which the registry was queried. However, Dr. Alkhouli cautioned that his data are best considered “hypothesis generating.”
“We need a randomized trial,” he said at the meeting sponsored by the Cardiovascular Research Foundation. He pointed out that this is a complex population for which multiple variables might have skewed results when data are analyzed retrospectively. Not least, those MR patients with cardiogenic shock in the database considered for TEER might well have been relatively healthy and not representative of an unselected population with both MR and cardiogenic shock.
The question might be better answered by the multicenter Canadian trial CAPITAL MINOS, which has just started. Described in an article in the American Heart Journal, it has a planned enrollment of about 150 MR patients with cardiogenic shock randomized to TEER or medical therapy. Results are expected in about 1 year, according to Dr. Alkhouli.
But regarding the present analysis, Dr. Alkhouli did note that sensitivity analyses conducted within his data across risk factors, such as degenerative versus nondegenerative MR, low (< 30%) versus higher left ventricular ejection fraction (LVEF), and presence or absence of an acute coronary syndrome (ACS), consistently supported a benefit from intervention.
Also, cardiogenic shock did not appear to be a factor in device failure, according to Dr. Alkhouli, addressing a potential criticism that cardiogenic shock was an underlying reason for device failure.
More than 90% in NYHA class III or IV heart failure
In this study, the mean age was 73 years. More than 90% were in class III or IV heart failure in the 2 weeks prior to TEER. More than half had established coronary artery disease. Other concomitant cardiovascular morbidities, including atrial fibrillation or flutter (65%), prior MI (39%), and prior stroke or transient ischemic attach (> 10%) were well represented.
When those with device success were compared with those with device failure, the risk profile was comparable. The predicted STS (Society of Thoracic Surgeons) mortality for mitral valve repair among these two groups was 14.8% versus 15% (P = 0.97), respectively.
However, those with device failure did have a lower baseline left ventricular ejection fraction (40.7% vs. 42.9%; P = .009) and a greater prevalence of moderate-to-severe or severe MR (96.1% vs. 84.9%; P < 0.001).
The growing experience with TEER means that benefit has now been shown in several complicated MR groups, such as those with severe ventricular dysfunction, renal insufficiency, and obstructive lung disease. This was a rationale for looking at the impact or repairing MR in patients with cardiogenic shock.
It is a pressing question, according to Dr. Alkhouli. He cited studies suggesting that up to 20% of patients hospitalized for cardiogenic shock have at least moderate-to-severe MR. Conversely, cardiogenic shock is not an uncommon finding in patients with MR.
While Dr. Alkhouli acknowledged that the many variables influencing outcome in patients with MR and cardiogenic shock will make a randomized trial “challenging,” many experts echoed this concern and even expressed some skepticism about the potential for an unbiased trial.
Data confirm MR repair is safe during shock
“These data do show that repair of MR is safe in patients safe in patients with cardiogenic shock,” said Anita W. Asgar, MD, an interventional cardiologist associated with the Montreal Heart Institute. She noted that there was a 5- to 6-day delay among the cardiogenic shock patients prior to undergoing MR repair in this analysis, potentially reflecting an elimination of those at very high risk. Similarly, she suggested that many interventionalists are likely to consider multiple variables before proceeding.
As a result, MR repair may not be amenable to randomization in a cardiogenic shock population, given that this decision is not typically undertaken out of the context of multiple variables.
“I am not sure that a clinical trial is ethical,” she said. She would expect that clinicians enrolling patients would only do so on a selective basis.
Alexandra J. Lansky, MD, Director of the Yale Heart and Vascular Research Program, Yale University, New Haven, Conn., also emphasized the difficulty of controlling for variables, such as the duration of cardiogenic shock, that influence decision-making.
Nevertheless, she called the data “very important” in that they at least lend some objective data for deciding whether to intervene a group of “challenging” patients not uncommonly faced in clinical practice.
Dr. Alkhouli reports financial relationships with Abbott Vascular, Boston Scientific, Johnson & Johnson, and Phillips. Dr. Asgar reports financial relationships with Abbott Vascular, Edwards Lifesciences, W.L. Gore & Associates, and Medtronic. Dr. Lasky reports no potential conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM TCT 2022
Walking intensity and step count are linked to health benefits
Each additional 2,000 steps per day – up to 10,000 – was associated with 8% to 11% fewer deaths and less heart disease and cancer, the researchers found. Walking quickly had an even stronger link to lower health risks.
The findings were reported in JAMA Internal Medicine. In a separate paper, published in JAMA Neurology, the researchers reported associations between walking and reduced risk of dementia.
Moving faster provides a health ‘bonus’
The findings expand on evidence in smaller studies of middle-aged individuals and older women that suggested health benefits from covering less than the widely promoted target of 10,000 steps a day.
The new study supports the ideas that “every step counts” and moving faster provides a health “bonus,” said one of its co-lead authors, Borja del Pozo Cruz, PhD, an associate professor at the University of Southern Denmark, Odense, and a senior researcher in health at the University of Cadiz, Spain.
Dr. Del Pozo Cruz and his coauthors analyzed median daily step counts for 78,500 adults aged 40-79 years in the U.K. Biobank database who agreed to wear an accelerometer for 1 week. Participants’ average age was 61. Fifty-five percent were women and 97% were White.
Steps were categorized as “incidental,” defined as a pace of less than 40 per minute, and “purposeful,” ones taken at the pace of 40 or more per minute. Researchers also calculated peak 30-minute cadence, the average of an individual’s 30 most active minutes in a day.
Participants’ health records were reviewed after 7 years. Each additional 2,000 steps taken was associated with lower all-cause mortality (mean rate of change [MRC] in the hazard ratio, –0.08; 95% confidence interval, –0.11 to –0.06); cardiovascular mortality (MRC, –0.10; 95% CI, –0.15 to –0.06), and cancer mortality (MRC, –0.11; 95% CI, –0.15 to –0.06).
Similar incremental reductions were observed in the incidence of heart disease, defined as fatal and nonfatal coronary heart disease, stroke, and heart failure; and a composite cancer outcome of 13 sites shown to be associated with low physical activity.
Both incidental and purposeful steps were linked to lower rates of mortality and disease. Particularly encouraging, the researchers said, was the benefit associated with incidental steps, which might be more feasible for some individuals than a planned walk.
The association with better outcomes was especially strong for peak-30 cadence, with individuals in the top fifth of intensity having a 34% lower mortality rate compared with those in the bottom fifth – an observation that researchers wrote “reflects the importance of the natural best effort relative to the individual’s capability.”
The analysis adjusted for a variety of factors including age, sex, race, smoking, alcohol use, fruit and vegetable consumption, medication use, family history of cardiovascular disease or cancer, and sleep quality. It also excluded participants who had deaths and illnesses within 2 years of a step assessment to minimize the problem of reverse causation, in which existing health problems cause participants to move less.
Data contribute evidence toward step count recommendations
The data are observational and do not prove cause and effect, the researchers noted. Still, the authors said the study “contributes critical evidence toward step count–based recommendations” for physical activity.
Guidelines of the United States and the World Health Organization recommend 150 minutes of moderately intense activity or 75 minutes of vigorous activity weekly plus strength training twice a week.
Given the proliferation of activity trackers in phones and watches, recommendations based on steps could be especially useful for individuals who don’t intentionally record their physical activity, the researchers wrote.
“It’s nice to have a study that puts some science behind steps counts,” cardiologist Nieca Goldberg, MD, a clinical associate professor of medicine at New York University, and a spokesperson for the American Heart Association, said of the findings.
Particularly important, said Dr. Goldberg, who was not involved in the study, is the lack of a minimum threshold for health benefits, since the 10,000-step target may be daunting for some individuals.
Only one in five participants in this latest study achieved 10,000 steps per day, according to the paper.
The authors wrote that promotion of lower step targets “may provide a more realistic and achievable goal for the general adult population,” and longevity gains “may be maximized simply by shifting away from the least-active end of the step-count distribution.”
Dr. Goldberg put it this way: “Take a walk. Try to aspire to 10,000 steps. But if you can only do 6,000 or 8,000, you get benefit there, too.”
Cathy Handy Marshall, MD, MPH, an assistant professor of oncology at Johns Hopkins University, Baltimore, who was not involved in the new study, said the findings can be used to guide “exercise prescriptions,” but more research is needed to tailor recommendations, particularly for individuals who cannot achieve high step counts.
Dr. Del Pozo Cruz said the findings need to be replicated in other populations.
The study authors, Dr. Goldberg, and Dr. Handy Marshall reported no relevant competing interests.
Each additional 2,000 steps per day – up to 10,000 – was associated with 8% to 11% fewer deaths and less heart disease and cancer, the researchers found. Walking quickly had an even stronger link to lower health risks.
The findings were reported in JAMA Internal Medicine. In a separate paper, published in JAMA Neurology, the researchers reported associations between walking and reduced risk of dementia.
Moving faster provides a health ‘bonus’
The findings expand on evidence in smaller studies of middle-aged individuals and older women that suggested health benefits from covering less than the widely promoted target of 10,000 steps a day.
The new study supports the ideas that “every step counts” and moving faster provides a health “bonus,” said one of its co-lead authors, Borja del Pozo Cruz, PhD, an associate professor at the University of Southern Denmark, Odense, and a senior researcher in health at the University of Cadiz, Spain.
Dr. Del Pozo Cruz and his coauthors analyzed median daily step counts for 78,500 adults aged 40-79 years in the U.K. Biobank database who agreed to wear an accelerometer for 1 week. Participants’ average age was 61. Fifty-five percent were women and 97% were White.
Steps were categorized as “incidental,” defined as a pace of less than 40 per minute, and “purposeful,” ones taken at the pace of 40 or more per minute. Researchers also calculated peak 30-minute cadence, the average of an individual’s 30 most active minutes in a day.
Participants’ health records were reviewed after 7 years. Each additional 2,000 steps taken was associated with lower all-cause mortality (mean rate of change [MRC] in the hazard ratio, –0.08; 95% confidence interval, –0.11 to –0.06); cardiovascular mortality (MRC, –0.10; 95% CI, –0.15 to –0.06), and cancer mortality (MRC, –0.11; 95% CI, –0.15 to –0.06).
Similar incremental reductions were observed in the incidence of heart disease, defined as fatal and nonfatal coronary heart disease, stroke, and heart failure; and a composite cancer outcome of 13 sites shown to be associated with low physical activity.
Both incidental and purposeful steps were linked to lower rates of mortality and disease. Particularly encouraging, the researchers said, was the benefit associated with incidental steps, which might be more feasible for some individuals than a planned walk.
The association with better outcomes was especially strong for peak-30 cadence, with individuals in the top fifth of intensity having a 34% lower mortality rate compared with those in the bottom fifth – an observation that researchers wrote “reflects the importance of the natural best effort relative to the individual’s capability.”
The analysis adjusted for a variety of factors including age, sex, race, smoking, alcohol use, fruit and vegetable consumption, medication use, family history of cardiovascular disease or cancer, and sleep quality. It also excluded participants who had deaths and illnesses within 2 years of a step assessment to minimize the problem of reverse causation, in which existing health problems cause participants to move less.
Data contribute evidence toward step count recommendations
The data are observational and do not prove cause and effect, the researchers noted. Still, the authors said the study “contributes critical evidence toward step count–based recommendations” for physical activity.
Guidelines of the United States and the World Health Organization recommend 150 minutes of moderately intense activity or 75 minutes of vigorous activity weekly plus strength training twice a week.
Given the proliferation of activity trackers in phones and watches, recommendations based on steps could be especially useful for individuals who don’t intentionally record their physical activity, the researchers wrote.
“It’s nice to have a study that puts some science behind steps counts,” cardiologist Nieca Goldberg, MD, a clinical associate professor of medicine at New York University, and a spokesperson for the American Heart Association, said of the findings.
Particularly important, said Dr. Goldberg, who was not involved in the study, is the lack of a minimum threshold for health benefits, since the 10,000-step target may be daunting for some individuals.
Only one in five participants in this latest study achieved 10,000 steps per day, according to the paper.
The authors wrote that promotion of lower step targets “may provide a more realistic and achievable goal for the general adult population,” and longevity gains “may be maximized simply by shifting away from the least-active end of the step-count distribution.”
Dr. Goldberg put it this way: “Take a walk. Try to aspire to 10,000 steps. But if you can only do 6,000 or 8,000, you get benefit there, too.”
Cathy Handy Marshall, MD, MPH, an assistant professor of oncology at Johns Hopkins University, Baltimore, who was not involved in the new study, said the findings can be used to guide “exercise prescriptions,” but more research is needed to tailor recommendations, particularly for individuals who cannot achieve high step counts.
Dr. Del Pozo Cruz said the findings need to be replicated in other populations.
The study authors, Dr. Goldberg, and Dr. Handy Marshall reported no relevant competing interests.
Each additional 2,000 steps per day – up to 10,000 – was associated with 8% to 11% fewer deaths and less heart disease and cancer, the researchers found. Walking quickly had an even stronger link to lower health risks.
The findings were reported in JAMA Internal Medicine. In a separate paper, published in JAMA Neurology, the researchers reported associations between walking and reduced risk of dementia.
Moving faster provides a health ‘bonus’
The findings expand on evidence in smaller studies of middle-aged individuals and older women that suggested health benefits from covering less than the widely promoted target of 10,000 steps a day.
The new study supports the ideas that “every step counts” and moving faster provides a health “bonus,” said one of its co-lead authors, Borja del Pozo Cruz, PhD, an associate professor at the University of Southern Denmark, Odense, and a senior researcher in health at the University of Cadiz, Spain.
Dr. Del Pozo Cruz and his coauthors analyzed median daily step counts for 78,500 adults aged 40-79 years in the U.K. Biobank database who agreed to wear an accelerometer for 1 week. Participants’ average age was 61. Fifty-five percent were women and 97% were White.
Steps were categorized as “incidental,” defined as a pace of less than 40 per minute, and “purposeful,” ones taken at the pace of 40 or more per minute. Researchers also calculated peak 30-minute cadence, the average of an individual’s 30 most active minutes in a day.
Participants’ health records were reviewed after 7 years. Each additional 2,000 steps taken was associated with lower all-cause mortality (mean rate of change [MRC] in the hazard ratio, –0.08; 95% confidence interval, –0.11 to –0.06); cardiovascular mortality (MRC, –0.10; 95% CI, –0.15 to –0.06), and cancer mortality (MRC, –0.11; 95% CI, –0.15 to –0.06).
Similar incremental reductions were observed in the incidence of heart disease, defined as fatal and nonfatal coronary heart disease, stroke, and heart failure; and a composite cancer outcome of 13 sites shown to be associated with low physical activity.
Both incidental and purposeful steps were linked to lower rates of mortality and disease. Particularly encouraging, the researchers said, was the benefit associated with incidental steps, which might be more feasible for some individuals than a planned walk.
The association with better outcomes was especially strong for peak-30 cadence, with individuals in the top fifth of intensity having a 34% lower mortality rate compared with those in the bottom fifth – an observation that researchers wrote “reflects the importance of the natural best effort relative to the individual’s capability.”
The analysis adjusted for a variety of factors including age, sex, race, smoking, alcohol use, fruit and vegetable consumption, medication use, family history of cardiovascular disease or cancer, and sleep quality. It also excluded participants who had deaths and illnesses within 2 years of a step assessment to minimize the problem of reverse causation, in which existing health problems cause participants to move less.
Data contribute evidence toward step count recommendations
The data are observational and do not prove cause and effect, the researchers noted. Still, the authors said the study “contributes critical evidence toward step count–based recommendations” for physical activity.
Guidelines of the United States and the World Health Organization recommend 150 minutes of moderately intense activity or 75 minutes of vigorous activity weekly plus strength training twice a week.
Given the proliferation of activity trackers in phones and watches, recommendations based on steps could be especially useful for individuals who don’t intentionally record their physical activity, the researchers wrote.
“It’s nice to have a study that puts some science behind steps counts,” cardiologist Nieca Goldberg, MD, a clinical associate professor of medicine at New York University, and a spokesperson for the American Heart Association, said of the findings.
Particularly important, said Dr. Goldberg, who was not involved in the study, is the lack of a minimum threshold for health benefits, since the 10,000-step target may be daunting for some individuals.
Only one in five participants in this latest study achieved 10,000 steps per day, according to the paper.
The authors wrote that promotion of lower step targets “may provide a more realistic and achievable goal for the general adult population,” and longevity gains “may be maximized simply by shifting away from the least-active end of the step-count distribution.”
Dr. Goldberg put it this way: “Take a walk. Try to aspire to 10,000 steps. But if you can only do 6,000 or 8,000, you get benefit there, too.”
Cathy Handy Marshall, MD, MPH, an assistant professor of oncology at Johns Hopkins University, Baltimore, who was not involved in the new study, said the findings can be used to guide “exercise prescriptions,” but more research is needed to tailor recommendations, particularly for individuals who cannot achieve high step counts.
Dr. Del Pozo Cruz said the findings need to be replicated in other populations.
The study authors, Dr. Goldberg, and Dr. Handy Marshall reported no relevant competing interests.
FROM JAMA INTERNAL MEDICINE
TBI is an unrecognized risk factor for cardiovascular disease
(CVD). More severe TBI is associated with higher risk of CVD, new research shows.
Given the relatively young age of post-9/11–era veterans with TBI, there may be an increased burden of heart disease in the future as these veterans age and develop traditional risk factors for CVD, the investigators, led by Ian J. Stewart, MD, with Uniformed Services University, Bethesda, Md., wrote.
The study was published online in JAMA Neurology.
Novel data
Since Sept. 11, 2001, 4.5 million people have served in the U.S. military, with their time in service defined by the long-running wars in Iraq and Afghanistan. Estimates suggest that up to 20% of post-9/11 veterans sustained a TBI.
While some evidence suggests that TBI increases the risk of CVD, prior reports have focused mainly on cerebrovascular outcomes. Until now, the potential association of TBI with CVD has not been comprehensively examined in post-9/11–era veterans.
The retrospective cohort study included 1,559,928 predominantly male post-9/11 veterans, including 301,169 (19.3%) with a history of TBI and 1,258,759 (81%) with no TBI history.
In fully adjusted models, compared with veterans with no TBI history, a history of mild, moderate/severe, or penetrating TBI was associated with increased risk of developing the composite CVD endpoint (coronary artery disease, stroke, peripheral artery disease, and CVD death).
TBIs of all severities were associated with the individual components of the composite outcome, except penetrating TBI and CVD death.
“The association of TBI with subsequent CVD was not attenuated in multivariable models, suggesting that TBI may be accounting for risk that is independent from the other variables,” Dr. Stewart and colleagues wrote.
They noted that the risk was highest shortly after injury, but TBI remained significantly associated with CVD for years after the initial insult.
Why TBI may raise the risk of subsequent CVD remains unclear.
It’s possible that patients with TBI develop more traditional risk factors for CVD through time than do patients without TBI. A study in mice found that TBI led to increased rates of atherosclerosis, the researchers said.
An additional mechanism may be disruption of autonomic regulation, which has been known to occur after TBI.
Another potential pathway is through mental health diagnoses, such as posttraumatic stress disorder; a large body of work has identified associations between PTSD and CVD, including among post-9/11 veterans.
Further work is needed to determine how this risk can be modified to improve outcomes for post-9/11–era veterans, the researchers write.
Unrecognized CVD risk factor?
Reached for comment, Shaheen E. Lakhan, MD, PhD, a neurologist and researcher from Boston who wasn’t involved in the study, said the effects of TBI on heart health are “very underreported, and most clinicians would not make the link.”
“When the brain suffers a traumatic injury, it activates a cascade of neuro-inflammation that goes haywire in an attempt to protect further brain damage. Oftentimes, these inflammatory by-products leak into the body, especially in trauma, when the barriers are broken between brain and body, and can cause systemic body inflammation, which is well associated with heart disease,” Dr. Lakhan said.
In addition, Dr. Lakhan said, “TBI itself localized to just the brain can negatively affect good health habits, leading to worsening heart health, too.”
“Research like this brings light where not much exists and underscores the importance of protecting our brains from physical trauma,” he said.
The study was supported by the assistant secretary of defense for health affairs, endorsed by the Department of Defense through the Psychological Health/Traumatic Brain Injury Research Program Long-Term Impact of Military-Relevant Brain Injury Consortium, and by the U.S. Department of Veterans Affairs. Dr. Stewart and Dr. Lakhan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(CVD). More severe TBI is associated with higher risk of CVD, new research shows.
Given the relatively young age of post-9/11–era veterans with TBI, there may be an increased burden of heart disease in the future as these veterans age and develop traditional risk factors for CVD, the investigators, led by Ian J. Stewart, MD, with Uniformed Services University, Bethesda, Md., wrote.
The study was published online in JAMA Neurology.
Novel data
Since Sept. 11, 2001, 4.5 million people have served in the U.S. military, with their time in service defined by the long-running wars in Iraq and Afghanistan. Estimates suggest that up to 20% of post-9/11 veterans sustained a TBI.
While some evidence suggests that TBI increases the risk of CVD, prior reports have focused mainly on cerebrovascular outcomes. Until now, the potential association of TBI with CVD has not been comprehensively examined in post-9/11–era veterans.
The retrospective cohort study included 1,559,928 predominantly male post-9/11 veterans, including 301,169 (19.3%) with a history of TBI and 1,258,759 (81%) with no TBI history.
In fully adjusted models, compared with veterans with no TBI history, a history of mild, moderate/severe, or penetrating TBI was associated with increased risk of developing the composite CVD endpoint (coronary artery disease, stroke, peripheral artery disease, and CVD death).
TBIs of all severities were associated with the individual components of the composite outcome, except penetrating TBI and CVD death.
“The association of TBI with subsequent CVD was not attenuated in multivariable models, suggesting that TBI may be accounting for risk that is independent from the other variables,” Dr. Stewart and colleagues wrote.
They noted that the risk was highest shortly after injury, but TBI remained significantly associated with CVD for years after the initial insult.
Why TBI may raise the risk of subsequent CVD remains unclear.
It’s possible that patients with TBI develop more traditional risk factors for CVD through time than do patients without TBI. A study in mice found that TBI led to increased rates of atherosclerosis, the researchers said.
An additional mechanism may be disruption of autonomic regulation, which has been known to occur after TBI.
Another potential pathway is through mental health diagnoses, such as posttraumatic stress disorder; a large body of work has identified associations between PTSD and CVD, including among post-9/11 veterans.
Further work is needed to determine how this risk can be modified to improve outcomes for post-9/11–era veterans, the researchers write.
Unrecognized CVD risk factor?
Reached for comment, Shaheen E. Lakhan, MD, PhD, a neurologist and researcher from Boston who wasn’t involved in the study, said the effects of TBI on heart health are “very underreported, and most clinicians would not make the link.”
“When the brain suffers a traumatic injury, it activates a cascade of neuro-inflammation that goes haywire in an attempt to protect further brain damage. Oftentimes, these inflammatory by-products leak into the body, especially in trauma, when the barriers are broken between brain and body, and can cause systemic body inflammation, which is well associated with heart disease,” Dr. Lakhan said.
In addition, Dr. Lakhan said, “TBI itself localized to just the brain can negatively affect good health habits, leading to worsening heart health, too.”
“Research like this brings light where not much exists and underscores the importance of protecting our brains from physical trauma,” he said.
The study was supported by the assistant secretary of defense for health affairs, endorsed by the Department of Defense through the Psychological Health/Traumatic Brain Injury Research Program Long-Term Impact of Military-Relevant Brain Injury Consortium, and by the U.S. Department of Veterans Affairs. Dr. Stewart and Dr. Lakhan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(CVD). More severe TBI is associated with higher risk of CVD, new research shows.
Given the relatively young age of post-9/11–era veterans with TBI, there may be an increased burden of heart disease in the future as these veterans age and develop traditional risk factors for CVD, the investigators, led by Ian J. Stewart, MD, with Uniformed Services University, Bethesda, Md., wrote.
The study was published online in JAMA Neurology.
Novel data
Since Sept. 11, 2001, 4.5 million people have served in the U.S. military, with their time in service defined by the long-running wars in Iraq and Afghanistan. Estimates suggest that up to 20% of post-9/11 veterans sustained a TBI.
While some evidence suggests that TBI increases the risk of CVD, prior reports have focused mainly on cerebrovascular outcomes. Until now, the potential association of TBI with CVD has not been comprehensively examined in post-9/11–era veterans.
The retrospective cohort study included 1,559,928 predominantly male post-9/11 veterans, including 301,169 (19.3%) with a history of TBI and 1,258,759 (81%) with no TBI history.
In fully adjusted models, compared with veterans with no TBI history, a history of mild, moderate/severe, or penetrating TBI was associated with increased risk of developing the composite CVD endpoint (coronary artery disease, stroke, peripheral artery disease, and CVD death).
TBIs of all severities were associated with the individual components of the composite outcome, except penetrating TBI and CVD death.
“The association of TBI with subsequent CVD was not attenuated in multivariable models, suggesting that TBI may be accounting for risk that is independent from the other variables,” Dr. Stewart and colleagues wrote.
They noted that the risk was highest shortly after injury, but TBI remained significantly associated with CVD for years after the initial insult.
Why TBI may raise the risk of subsequent CVD remains unclear.
It’s possible that patients with TBI develop more traditional risk factors for CVD through time than do patients without TBI. A study in mice found that TBI led to increased rates of atherosclerosis, the researchers said.
An additional mechanism may be disruption of autonomic regulation, which has been known to occur after TBI.
Another potential pathway is through mental health diagnoses, such as posttraumatic stress disorder; a large body of work has identified associations between PTSD and CVD, including among post-9/11 veterans.
Further work is needed to determine how this risk can be modified to improve outcomes for post-9/11–era veterans, the researchers write.
Unrecognized CVD risk factor?
Reached for comment, Shaheen E. Lakhan, MD, PhD, a neurologist and researcher from Boston who wasn’t involved in the study, said the effects of TBI on heart health are “very underreported, and most clinicians would not make the link.”
“When the brain suffers a traumatic injury, it activates a cascade of neuro-inflammation that goes haywire in an attempt to protect further brain damage. Oftentimes, these inflammatory by-products leak into the body, especially in trauma, when the barriers are broken between brain and body, and can cause systemic body inflammation, which is well associated with heart disease,” Dr. Lakhan said.
In addition, Dr. Lakhan said, “TBI itself localized to just the brain can negatively affect good health habits, leading to worsening heart health, too.”
“Research like this brings light where not much exists and underscores the importance of protecting our brains from physical trauma,” he said.
The study was supported by the assistant secretary of defense for health affairs, endorsed by the Department of Defense through the Psychological Health/Traumatic Brain Injury Research Program Long-Term Impact of Military-Relevant Brain Injury Consortium, and by the U.S. Department of Veterans Affairs. Dr. Stewart and Dr. Lakhan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
PARADISE-MI results obscured as post hoc analysis finds flaws
A post hoc analysis of the PARADISE-MI trial, although not intended to alter the conclusions generated by the published data, suggests that clinically relevant benefits were obscured, providing the basis for recommending different analyses for future studies that are more suited to capture the most clinically significant endpoints.
“What these data show us is that we need clinical trial designs moving towards more pragmatic information that better reflect clinical practice,” reported Otavio Berwanger, MD, PhD, director of the Academic Research Organization at Hospital Israelita Albert Einstein, São Paulo, Brazil.
The reevaluation of the PARADISE-MI data, presented at the annual congress of the European Society of Cardiology in Barcelona, was based on a win ratio analysis and on the inclusion of investigator-reported endpoints, not just adjudicated events. Both appear to reveal clinically meaningful benefits not reflected in the published study, according to Dr. Berwanger.
In PARADISE-MI, which was published in the New England Journal of Medicine last year, more than 5,500 patients were randomized to the angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan or the ACE inhibitor ramipril after a myocardial infarction. A reduced left ventricular ejection fraction (LVEF), pulmonary congestion, or both were required for enrollment.
For the primary composite outcomes of death from cardiovascular (CV) causes or incident heart failure, the ARNI had a 10% numerical advantage, but it did not reach statistical significance (hazard ratio [HR], 0.90; P = .17).
“PARADISE-MI was a neutral trial. This post hoc analysis will not change that result,” Dr. Berwanger emphasized. However, the post hoc analysis does provide a basis for exploring why conventional trial designs might not be providing answers that are relevant and helpful for clinical practice.
New analysis provides positive trial result
When the data from PARADISE-MI are reevaluated in a hierarchical win ratio analysis with CV death serving as the most severe and important outcome, the principal conclusion changes. Whether events are reevaluated in this format by the clinical events committee (CEC) or by investigators, there is a greater number of total wins than total losses for the ARNI. Combined, sacubitril/valsartan was associated with a win ratio of 1.17 (95% confidence interval, 1.03-1.33; P = 0.015) over ramipril.
Using a sports analogy, Dr. Berwanger explained that the win ratio analysis divides the total number of wins to the total number of losses to provide a much more clinically relevant approach to keeping score. It also used a hierarchical analysis so that the most serious and important events are considered first.
In addition to CV death, this analysis included first hospitalization for heart failure and first outpatient heart failure events. CEC-defined events and events reported by investigators were evaluated separately.
The ARNI had more wins than losses in every category for all outcomes, whether CEC adjudicated or investigator reported, but most of this benefit was generated by the endpoint of CEC-adjudicated CV deaths. This accounted for 36.9% of all events (investigator-documented CV death accounted for 0.7%). This is important because PARADISE-MI, like many standard trials, was conducted on a time-to-primary event basis.
“In this type of analysis, the first event is what counts. Usually time-to-first-event analyses are dominated by nonfatal events,” Dr. Berwanger explained. He believes that placing more weight on the most serious events results in an emphasis on what outcomes are of greatest clinical interest.
In addition, Dr. Berwanger argued that it is important to consider investigator-reported events, not just CEC-adjudicated events. While adjudicated events improve the rigor of the data, Dr. Berwanger suggested it omits outcomes with which clinicians are most concerned.
Investigator, adjudicated outcomes differ
Again, using PARADISE-MI as an example, he reevaluated the primary outcome based on investigator reports. When investigator-reported events are included, the number of events increased in both the ARNI (443 vs. 338) and ramipril (516 vs. 373) arms, but the advantage of the ARNI over the ACE inhibitors now reached statistical significance (HR, 0.85; P = .01).
“The data suggest that maybe we should find definitions for adjudication that are closer to clinical judgment in the real world and clinical practice,” Dr. Berwanger said.
One possible explanation for the neutral result in PARADISE-MI is that benefit of an ARNI over an ACE inhibitor would only be expected in those at risk for progressive left ventricular dysfunction, and it is likely that a substantial proportion of patients enrolled in this trial recovered, according to Johann Bauersachs, MD, PhD, professor and head of cardiology at Hannover (Germany) Medical School.
“You cannot predict which patients with reduced LV function following an MI will go on to chronic remodeling and which will recover,” said Dr. Bauersachs, who was an ESC-invited discussant of Dr. Berwanger’s post hoc analysis.
He agreed that Dr. Berwanger has raised several important issues in standard trial design that might have prevented PARADISE-MI from showing a benefit from an ARNI, but he pointed out that there are other potential issues, such as the low use of mineralocorticoid antagonists in PARADISE-MI, that may have skewed results.
However, he agreed generally with the premise that there is a need for trial design likely to generate more clinically useful information.
“We have now seen the win-ratio approach used in several studies,” said Dr. Bauersachs, citing in particular the EMPULSE trial presented at the 2022 meeting of the American College of Cardiology. “It is a very useful tool, and I think we will be seeing it used more in the future.”
However, he indicated that the issues raised by Dr. Berwanger are not necessarily easily resolved. Dr. Bauersachs endorsed the effort to consider trial designs that generate data that are more immediately clinically applicable but suggested that different types of designs may be required for different types of clinical questions.
Dr. Berwanger reports financial relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Pfizer, Servier, and Novartis, which provided funding for the PARADISE-MI trial. Dr. Bauersachs reports financial relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Cardior, Corvia, CVRx, Novartis, Pfizer, Vifor, and Zoll.
A post hoc analysis of the PARADISE-MI trial, although not intended to alter the conclusions generated by the published data, suggests that clinically relevant benefits were obscured, providing the basis for recommending different analyses for future studies that are more suited to capture the most clinically significant endpoints.
“What these data show us is that we need clinical trial designs moving towards more pragmatic information that better reflect clinical practice,” reported Otavio Berwanger, MD, PhD, director of the Academic Research Organization at Hospital Israelita Albert Einstein, São Paulo, Brazil.
The reevaluation of the PARADISE-MI data, presented at the annual congress of the European Society of Cardiology in Barcelona, was based on a win ratio analysis and on the inclusion of investigator-reported endpoints, not just adjudicated events. Both appear to reveal clinically meaningful benefits not reflected in the published study, according to Dr. Berwanger.
In PARADISE-MI, which was published in the New England Journal of Medicine last year, more than 5,500 patients were randomized to the angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan or the ACE inhibitor ramipril after a myocardial infarction. A reduced left ventricular ejection fraction (LVEF), pulmonary congestion, or both were required for enrollment.
For the primary composite outcomes of death from cardiovascular (CV) causes or incident heart failure, the ARNI had a 10% numerical advantage, but it did not reach statistical significance (hazard ratio [HR], 0.90; P = .17).
“PARADISE-MI was a neutral trial. This post hoc analysis will not change that result,” Dr. Berwanger emphasized. However, the post hoc analysis does provide a basis for exploring why conventional trial designs might not be providing answers that are relevant and helpful for clinical practice.
New analysis provides positive trial result
When the data from PARADISE-MI are reevaluated in a hierarchical win ratio analysis with CV death serving as the most severe and important outcome, the principal conclusion changes. Whether events are reevaluated in this format by the clinical events committee (CEC) or by investigators, there is a greater number of total wins than total losses for the ARNI. Combined, sacubitril/valsartan was associated with a win ratio of 1.17 (95% confidence interval, 1.03-1.33; P = 0.015) over ramipril.
Using a sports analogy, Dr. Berwanger explained that the win ratio analysis divides the total number of wins to the total number of losses to provide a much more clinically relevant approach to keeping score. It also used a hierarchical analysis so that the most serious and important events are considered first.
In addition to CV death, this analysis included first hospitalization for heart failure and first outpatient heart failure events. CEC-defined events and events reported by investigators were evaluated separately.
The ARNI had more wins than losses in every category for all outcomes, whether CEC adjudicated or investigator reported, but most of this benefit was generated by the endpoint of CEC-adjudicated CV deaths. This accounted for 36.9% of all events (investigator-documented CV death accounted for 0.7%). This is important because PARADISE-MI, like many standard trials, was conducted on a time-to-primary event basis.
“In this type of analysis, the first event is what counts. Usually time-to-first-event analyses are dominated by nonfatal events,” Dr. Berwanger explained. He believes that placing more weight on the most serious events results in an emphasis on what outcomes are of greatest clinical interest.
In addition, Dr. Berwanger argued that it is important to consider investigator-reported events, not just CEC-adjudicated events. While adjudicated events improve the rigor of the data, Dr. Berwanger suggested it omits outcomes with which clinicians are most concerned.
Investigator, adjudicated outcomes differ
Again, using PARADISE-MI as an example, he reevaluated the primary outcome based on investigator reports. When investigator-reported events are included, the number of events increased in both the ARNI (443 vs. 338) and ramipril (516 vs. 373) arms, but the advantage of the ARNI over the ACE inhibitors now reached statistical significance (HR, 0.85; P = .01).
“The data suggest that maybe we should find definitions for adjudication that are closer to clinical judgment in the real world and clinical practice,” Dr. Berwanger said.
One possible explanation for the neutral result in PARADISE-MI is that benefit of an ARNI over an ACE inhibitor would only be expected in those at risk for progressive left ventricular dysfunction, and it is likely that a substantial proportion of patients enrolled in this trial recovered, according to Johann Bauersachs, MD, PhD, professor and head of cardiology at Hannover (Germany) Medical School.
“You cannot predict which patients with reduced LV function following an MI will go on to chronic remodeling and which will recover,” said Dr. Bauersachs, who was an ESC-invited discussant of Dr. Berwanger’s post hoc analysis.
He agreed that Dr. Berwanger has raised several important issues in standard trial design that might have prevented PARADISE-MI from showing a benefit from an ARNI, but he pointed out that there are other potential issues, such as the low use of mineralocorticoid antagonists in PARADISE-MI, that may have skewed results.
However, he agreed generally with the premise that there is a need for trial design likely to generate more clinically useful information.
“We have now seen the win-ratio approach used in several studies,” said Dr. Bauersachs, citing in particular the EMPULSE trial presented at the 2022 meeting of the American College of Cardiology. “It is a very useful tool, and I think we will be seeing it used more in the future.”
However, he indicated that the issues raised by Dr. Berwanger are not necessarily easily resolved. Dr. Bauersachs endorsed the effort to consider trial designs that generate data that are more immediately clinically applicable but suggested that different types of designs may be required for different types of clinical questions.
Dr. Berwanger reports financial relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Pfizer, Servier, and Novartis, which provided funding for the PARADISE-MI trial. Dr. Bauersachs reports financial relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Cardior, Corvia, CVRx, Novartis, Pfizer, Vifor, and Zoll.
A post hoc analysis of the PARADISE-MI trial, although not intended to alter the conclusions generated by the published data, suggests that clinically relevant benefits were obscured, providing the basis for recommending different analyses for future studies that are more suited to capture the most clinically significant endpoints.
“What these data show us is that we need clinical trial designs moving towards more pragmatic information that better reflect clinical practice,” reported Otavio Berwanger, MD, PhD, director of the Academic Research Organization at Hospital Israelita Albert Einstein, São Paulo, Brazil.
The reevaluation of the PARADISE-MI data, presented at the annual congress of the European Society of Cardiology in Barcelona, was based on a win ratio analysis and on the inclusion of investigator-reported endpoints, not just adjudicated events. Both appear to reveal clinically meaningful benefits not reflected in the published study, according to Dr. Berwanger.
In PARADISE-MI, which was published in the New England Journal of Medicine last year, more than 5,500 patients were randomized to the angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan or the ACE inhibitor ramipril after a myocardial infarction. A reduced left ventricular ejection fraction (LVEF), pulmonary congestion, or both were required for enrollment.
For the primary composite outcomes of death from cardiovascular (CV) causes or incident heart failure, the ARNI had a 10% numerical advantage, but it did not reach statistical significance (hazard ratio [HR], 0.90; P = .17).
“PARADISE-MI was a neutral trial. This post hoc analysis will not change that result,” Dr. Berwanger emphasized. However, the post hoc analysis does provide a basis for exploring why conventional trial designs might not be providing answers that are relevant and helpful for clinical practice.
New analysis provides positive trial result
When the data from PARADISE-MI are reevaluated in a hierarchical win ratio analysis with CV death serving as the most severe and important outcome, the principal conclusion changes. Whether events are reevaluated in this format by the clinical events committee (CEC) or by investigators, there is a greater number of total wins than total losses for the ARNI. Combined, sacubitril/valsartan was associated with a win ratio of 1.17 (95% confidence interval, 1.03-1.33; P = 0.015) over ramipril.
Using a sports analogy, Dr. Berwanger explained that the win ratio analysis divides the total number of wins to the total number of losses to provide a much more clinically relevant approach to keeping score. It also used a hierarchical analysis so that the most serious and important events are considered first.
In addition to CV death, this analysis included first hospitalization for heart failure and first outpatient heart failure events. CEC-defined events and events reported by investigators were evaluated separately.
The ARNI had more wins than losses in every category for all outcomes, whether CEC adjudicated or investigator reported, but most of this benefit was generated by the endpoint of CEC-adjudicated CV deaths. This accounted for 36.9% of all events (investigator-documented CV death accounted for 0.7%). This is important because PARADISE-MI, like many standard trials, was conducted on a time-to-primary event basis.
“In this type of analysis, the first event is what counts. Usually time-to-first-event analyses are dominated by nonfatal events,” Dr. Berwanger explained. He believes that placing more weight on the most serious events results in an emphasis on what outcomes are of greatest clinical interest.
In addition, Dr. Berwanger argued that it is important to consider investigator-reported events, not just CEC-adjudicated events. While adjudicated events improve the rigor of the data, Dr. Berwanger suggested it omits outcomes with which clinicians are most concerned.
Investigator, adjudicated outcomes differ
Again, using PARADISE-MI as an example, he reevaluated the primary outcome based on investigator reports. When investigator-reported events are included, the number of events increased in both the ARNI (443 vs. 338) and ramipril (516 vs. 373) arms, but the advantage of the ARNI over the ACE inhibitors now reached statistical significance (HR, 0.85; P = .01).
“The data suggest that maybe we should find definitions for adjudication that are closer to clinical judgment in the real world and clinical practice,” Dr. Berwanger said.
One possible explanation for the neutral result in PARADISE-MI is that benefit of an ARNI over an ACE inhibitor would only be expected in those at risk for progressive left ventricular dysfunction, and it is likely that a substantial proportion of patients enrolled in this trial recovered, according to Johann Bauersachs, MD, PhD, professor and head of cardiology at Hannover (Germany) Medical School.
“You cannot predict which patients with reduced LV function following an MI will go on to chronic remodeling and which will recover,” said Dr. Bauersachs, who was an ESC-invited discussant of Dr. Berwanger’s post hoc analysis.
He agreed that Dr. Berwanger has raised several important issues in standard trial design that might have prevented PARADISE-MI from showing a benefit from an ARNI, but he pointed out that there are other potential issues, such as the low use of mineralocorticoid antagonists in PARADISE-MI, that may have skewed results.
However, he agreed generally with the premise that there is a need for trial design likely to generate more clinically useful information.
“We have now seen the win-ratio approach used in several studies,” said Dr. Bauersachs, citing in particular the EMPULSE trial presented at the 2022 meeting of the American College of Cardiology. “It is a very useful tool, and I think we will be seeing it used more in the future.”
However, he indicated that the issues raised by Dr. Berwanger are not necessarily easily resolved. Dr. Bauersachs endorsed the effort to consider trial designs that generate data that are more immediately clinically applicable but suggested that different types of designs may be required for different types of clinical questions.
Dr. Berwanger reports financial relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Pfizer, Servier, and Novartis, which provided funding for the PARADISE-MI trial. Dr. Bauersachs reports financial relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Cardior, Corvia, CVRx, Novartis, Pfizer, Vifor, and Zoll.
FROM ESC CONGRESS 2022