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ASH releases guidelines on managing cardiopulmonary and kidney disease in SCD
ORLANDO – It is good practice to consult with a pulmonary hypertension (PH) expert before referring a patient with sickle cell disease (SCD) for right-heart catheterization or PH evaluation, according to new American Society of Hematology guidelines for the screening and management of cardiopulmonary and kidney disease in patients with SCD.
That “Good Practice” recommendation is one of several included in the evidence-based guidelines published Dec. 10 in Blood Advances and highlighted during a Special Education Session at the annual ASH meeting.
The guidelines provide 10 main recommendations intended to “support patients, clinicians, and other health care professionals in their decisions about screening, diagnosis, and management of cardiopulmonary and renal complications of SCD,” wrote Robert I. Liem, MD, of Ann & Robert H. Lurie Children’s Hospital of Chicago and colleagues.
The recommendations, agreed upon by a multidisciplinary guideline panel, relate to screening, diagnosis, and management of PH, pulmonary arterial hypertension (PAH), hypertension, proteinuria and chronic kidney disease, and venous thromboembolism (VTE). Most are “conditional,” as opposed to “strong,” because of a paucity of direct, high-quality outcomes data, and they are accompanied by the Good Practice Statements, descriptive remarks and caveats based on the available data, as well as suggestions for future research.
At the special ASH session, Ankit A. Desai, MD, highlighted some of the recommendations and discussed considerations for their practical application.
The Good Practice Statement on consulting a specialist before referring a patient for PH relates specifically to Recommendations 2a and 2b on the management of abnormal echocardiography, explained Dr. Desai of Indiana University, Indianapolis.
For asymptomatic children and adults with SCD and an isolated peak tricuspid regurgitant jet velocity (TRJV) of at least 2.5-2.9 m/s on echocardiography, the panel recommends against right-heart catheterization (Recommendation 2a, conditional), he said.
For children and adults with SCD and a peak TRJV of at least 2.5 m/s who also have a reduced 6-minute walk distance (6MWD) and/or elevated N-terminal proB-type natriuretic peptide (NT-proBNP), the panel supports right-heart catheterization (Recommendation 2b, conditional).
Dr. Desai noted that the 2.5 m/s threshold was found to be suboptimal when used as the sole criteria for right-heart catheterization. Using that threshold alone is associated with “moderate to large” harms, such as starting inappropriate PH-specific therapies and/or performing unnecessary right-heart catheterization. However, when used in combination with 6MWD, the predictive capacity improved significantly, and the risk for potential harm was low, he explained.
Another Good Practice Statement included in the guidelines, and relevant to these recommendations on managing abnormal echocardiography, addresses the importance of basing decisions about the need for right-heart catheterization on echocardiograms obtained at steady state rather than during acute illness, such as during hospitalization for pain or acute chest syndrome.
This is in part because of technical factors, Dr. Desai said.
“We know that repeating [echocardiography] is something that should be considered in patients because ... results vary – sometimes quite a bit – from study to study,” he said.
As for the cutoff values for 6MWD and NT-proBNP, “a decent amount of literature” suggests that less than 333 m and less than 160 pg/ml, respectively, are good thresholds, he said.
“Importantly, this should all be taken in the context of good clinical judgment ... along with discussion with a PH expert,” he added.
The full guidelines are available, along with additional ASH guidelines on immune thrombocytopenia and prevention of venous thromboembolism in surgical hospitalized patients, at the ASH publications website.
Of note, the SCD guidelines on cardiopulmonary disease and kidney disease are one of five sets of SCD guidelines that have been in development; these are the first of those to be published. The remaining four sets of guidelines will address pain, cerebrovascular complications, transfusion, and hematopoietic stem cell transplant. All will be published in Blood Advances, and according to Dr. Liem, the transfusion medicine guidelines have been accepted and should be published in January 2020, followed by those for cerebrovascular complications. Publication of the pain and transplant guidelines are anticipated later in 2020.
Dr. Liem and Dr. Desai reported having no conflicts of interest.
ORLANDO – It is good practice to consult with a pulmonary hypertension (PH) expert before referring a patient with sickle cell disease (SCD) for right-heart catheterization or PH evaluation, according to new American Society of Hematology guidelines for the screening and management of cardiopulmonary and kidney disease in patients with SCD.
That “Good Practice” recommendation is one of several included in the evidence-based guidelines published Dec. 10 in Blood Advances and highlighted during a Special Education Session at the annual ASH meeting.
The guidelines provide 10 main recommendations intended to “support patients, clinicians, and other health care professionals in their decisions about screening, diagnosis, and management of cardiopulmonary and renal complications of SCD,” wrote Robert I. Liem, MD, of Ann & Robert H. Lurie Children’s Hospital of Chicago and colleagues.
The recommendations, agreed upon by a multidisciplinary guideline panel, relate to screening, diagnosis, and management of PH, pulmonary arterial hypertension (PAH), hypertension, proteinuria and chronic kidney disease, and venous thromboembolism (VTE). Most are “conditional,” as opposed to “strong,” because of a paucity of direct, high-quality outcomes data, and they are accompanied by the Good Practice Statements, descriptive remarks and caveats based on the available data, as well as suggestions for future research.
At the special ASH session, Ankit A. Desai, MD, highlighted some of the recommendations and discussed considerations for their practical application.
The Good Practice Statement on consulting a specialist before referring a patient for PH relates specifically to Recommendations 2a and 2b on the management of abnormal echocardiography, explained Dr. Desai of Indiana University, Indianapolis.
For asymptomatic children and adults with SCD and an isolated peak tricuspid regurgitant jet velocity (TRJV) of at least 2.5-2.9 m/s on echocardiography, the panel recommends against right-heart catheterization (Recommendation 2a, conditional), he said.
For children and adults with SCD and a peak TRJV of at least 2.5 m/s who also have a reduced 6-minute walk distance (6MWD) and/or elevated N-terminal proB-type natriuretic peptide (NT-proBNP), the panel supports right-heart catheterization (Recommendation 2b, conditional).
Dr. Desai noted that the 2.5 m/s threshold was found to be suboptimal when used as the sole criteria for right-heart catheterization. Using that threshold alone is associated with “moderate to large” harms, such as starting inappropriate PH-specific therapies and/or performing unnecessary right-heart catheterization. However, when used in combination with 6MWD, the predictive capacity improved significantly, and the risk for potential harm was low, he explained.
Another Good Practice Statement included in the guidelines, and relevant to these recommendations on managing abnormal echocardiography, addresses the importance of basing decisions about the need for right-heart catheterization on echocardiograms obtained at steady state rather than during acute illness, such as during hospitalization for pain or acute chest syndrome.
This is in part because of technical factors, Dr. Desai said.
“We know that repeating [echocardiography] is something that should be considered in patients because ... results vary – sometimes quite a bit – from study to study,” he said.
As for the cutoff values for 6MWD and NT-proBNP, “a decent amount of literature” suggests that less than 333 m and less than 160 pg/ml, respectively, are good thresholds, he said.
“Importantly, this should all be taken in the context of good clinical judgment ... along with discussion with a PH expert,” he added.
The full guidelines are available, along with additional ASH guidelines on immune thrombocytopenia and prevention of venous thromboembolism in surgical hospitalized patients, at the ASH publications website.
Of note, the SCD guidelines on cardiopulmonary disease and kidney disease are one of five sets of SCD guidelines that have been in development; these are the first of those to be published. The remaining four sets of guidelines will address pain, cerebrovascular complications, transfusion, and hematopoietic stem cell transplant. All will be published in Blood Advances, and according to Dr. Liem, the transfusion medicine guidelines have been accepted and should be published in January 2020, followed by those for cerebrovascular complications. Publication of the pain and transplant guidelines are anticipated later in 2020.
Dr. Liem and Dr. Desai reported having no conflicts of interest.
ORLANDO – It is good practice to consult with a pulmonary hypertension (PH) expert before referring a patient with sickle cell disease (SCD) for right-heart catheterization or PH evaluation, according to new American Society of Hematology guidelines for the screening and management of cardiopulmonary and kidney disease in patients with SCD.
That “Good Practice” recommendation is one of several included in the evidence-based guidelines published Dec. 10 in Blood Advances and highlighted during a Special Education Session at the annual ASH meeting.
The guidelines provide 10 main recommendations intended to “support patients, clinicians, and other health care professionals in their decisions about screening, diagnosis, and management of cardiopulmonary and renal complications of SCD,” wrote Robert I. Liem, MD, of Ann & Robert H. Lurie Children’s Hospital of Chicago and colleagues.
The recommendations, agreed upon by a multidisciplinary guideline panel, relate to screening, diagnosis, and management of PH, pulmonary arterial hypertension (PAH), hypertension, proteinuria and chronic kidney disease, and venous thromboembolism (VTE). Most are “conditional,” as opposed to “strong,” because of a paucity of direct, high-quality outcomes data, and they are accompanied by the Good Practice Statements, descriptive remarks and caveats based on the available data, as well as suggestions for future research.
At the special ASH session, Ankit A. Desai, MD, highlighted some of the recommendations and discussed considerations for their practical application.
The Good Practice Statement on consulting a specialist before referring a patient for PH relates specifically to Recommendations 2a and 2b on the management of abnormal echocardiography, explained Dr. Desai of Indiana University, Indianapolis.
For asymptomatic children and adults with SCD and an isolated peak tricuspid regurgitant jet velocity (TRJV) of at least 2.5-2.9 m/s on echocardiography, the panel recommends against right-heart catheterization (Recommendation 2a, conditional), he said.
For children and adults with SCD and a peak TRJV of at least 2.5 m/s who also have a reduced 6-minute walk distance (6MWD) and/or elevated N-terminal proB-type natriuretic peptide (NT-proBNP), the panel supports right-heart catheterization (Recommendation 2b, conditional).
Dr. Desai noted that the 2.5 m/s threshold was found to be suboptimal when used as the sole criteria for right-heart catheterization. Using that threshold alone is associated with “moderate to large” harms, such as starting inappropriate PH-specific therapies and/or performing unnecessary right-heart catheterization. However, when used in combination with 6MWD, the predictive capacity improved significantly, and the risk for potential harm was low, he explained.
Another Good Practice Statement included in the guidelines, and relevant to these recommendations on managing abnormal echocardiography, addresses the importance of basing decisions about the need for right-heart catheterization on echocardiograms obtained at steady state rather than during acute illness, such as during hospitalization for pain or acute chest syndrome.
This is in part because of technical factors, Dr. Desai said.
“We know that repeating [echocardiography] is something that should be considered in patients because ... results vary – sometimes quite a bit – from study to study,” he said.
As for the cutoff values for 6MWD and NT-proBNP, “a decent amount of literature” suggests that less than 333 m and less than 160 pg/ml, respectively, are good thresholds, he said.
“Importantly, this should all be taken in the context of good clinical judgment ... along with discussion with a PH expert,” he added.
The full guidelines are available, along with additional ASH guidelines on immune thrombocytopenia and prevention of venous thromboembolism in surgical hospitalized patients, at the ASH publications website.
Of note, the SCD guidelines on cardiopulmonary disease and kidney disease are one of five sets of SCD guidelines that have been in development; these are the first of those to be published. The remaining four sets of guidelines will address pain, cerebrovascular complications, transfusion, and hematopoietic stem cell transplant. All will be published in Blood Advances, and according to Dr. Liem, the transfusion medicine guidelines have been accepted and should be published in January 2020, followed by those for cerebrovascular complications. Publication of the pain and transplant guidelines are anticipated later in 2020.
Dr. Liem and Dr. Desai reported having no conflicts of interest.
EXPERT ANALYSIS FROM ASH 2019
Do women with diabetes need more CVD risk reduction than men?
BUSAN, SOUTH KOREA – Whether cardiovascular disease risk reduction efforts should be more aggressive in women than men with diabetes depends on how you interpret the data.
Two experts came to different conclusions on this question during a heated, but jovial, debate last week here at the International Diabetes Federation 2019 Congress.
Endocrinologist David Simmons, MB, BChir, Western Sydney University, Campbelltown, Australia, argued that diabetes erases the well-described life expectancy advantage of 4-7 years that women experience over men in the general population.
He also highlighted the fact that the heightened risk is of particular concern in both younger women and those with prior gestational diabetes.
But Timothy Davis, BMedSc, MB, BS, DPhil, an endocrinologist and general physician at Fremantle (Australia) Hospital, countered that the data only show the diabetes-attributable excess cardiovascular risk is higher in women than men, but that the absolute risk is actually greater in men.
Moreover, he argued, at least in type 1 diabetes, there is no evidence that more aggressive cardiovascular risk factor management improves outcomes.
Yes: Diabetes eliminates female CVD protection
Dr. Simmons began by pointing out that, although on average women die at an older age than men, it has been known for over 40 years that this “female protection” is lost in insulin-treated women, particularly as a result of their increased risk for cardiovascular disease.
In a 2015 meta-analysis of 26 studies, women with type 1 diabetes were found to have about a 37% greater risk of all-cause mortality, compared with men with the condition when mortality is contrasted with that of the general population, and twice the risk of both fatal and nonfatal vascular events.
The risk appeared to be greater in women who were younger at the time of diabetes diagnosis. “This is a really important point – the time we would want to intervene,” Dr. Simmons said.
In another meta-analysis of 30 studies including 2,307,694 individuals with type 2 diabetes and 252,491 deaths, the pooled women-to-men ratio of the standardized mortality ratio for all-cause mortality was 1.14.
In those with versus without type 2 diabetes, the pooled standardized mortality ratio in women was 2.30 and in men was 1.94, both significant, compared with those without diabetes.
And in a 2006 meta-analysis of 22 studies involving individuals with type 2 diabetes, the pooled data showed a 46% excess relative risk using standardized mortality ratios in women versus men for fatal coronary artery disease.
Meanwhile, in a 2018 meta-analysis of 68 studies involving nearly 1 million adults examining differences in occlusive vascular disease, after controlling for major vascular risk factors, diabetes roughly doubled the risk for occlusive vascular mortality in men (relative risk, 2.10), but tripled it in women (3.00).
Women with diabetes aged 35-59 years had the highest relative risk for death over follow-up across all age and sex groups: They had 5.5 times the excess risk, compared with those without diabetes, while the excess risk for men of that age was 2.3-fold.
“So very clearly, it’s these young women who are most at risk, “emphasized Dr. Simmons, who is an investigator for Novo Nordisk and a speaker for Medtronic, Novo Nordisk, and Sanofi.
Are disparities because of differences in cvd risk factor management?
The question has arisen whether the female/male differences might be because of differences in cardiovascular risk factor management, Simmons noted.
A 2015 American Heart Association statement laid out the evidence for lower prescribing of statins, aspirin, beta-blockers, and ACE inhibitors in women, compared with men, Dr. Simmons said.
And some studies suggest medication adherence is lower in women than men.
In terms of medications, fenofibrate appears to produce better outcomes in women than men, but there is no evidence of gender differences in the effects of statins, ACE inhibitors, or aspirin, Simmons said.
He also outlined the results of a 2008 study of 78,254 patients with acute myocardial infarction from 420 U.S. hospitals in 2001-2006.
Women were older, had more comorbidities, less often presented with ST-elevation myocardial infarction (STEMI), and had a higher rate of unadjusted in-hospital death (8.2% vs. 5.7%; P less than .0001) than men. Of the participants, 33% of women had diabetes, compared with 28% of men.
The in-hospital mortality difference disappeared after multivariable adjustment, but women with STEMI still had higher adjusted mortality rates than men.
“The underuse of evidence-based treatments and delayed reperfusion in women represent potential opportunities for reducing sex disparities in care and outcome after acute myocardial infarction,” the authors concluded.
“It’s very clear amongst our cardiology colleagues that something needs to be done and that we need more aggressive cardiological risk reduction in women,” Dr. Simmons said.
“The AHA has already decided this. It’s already a policy. So why are we having this debate?” he wondered.
He also pointed out that women with prior gestational diabetes are an exceptionally high–risk group, with a twofold excess risk for cardiovascular disease within the first 10 years post partum.
“We need to do something about this particularly high-risk group, independent of debates about gender,” Dr. Simmons emphasized. “Clearly, women with diabetes warrant more aggressive cardiovascular risk reduction than men with diabetes, especially at those younger ages,” he concluded.
No: Confusion about relative risk within each sex and absolute risk
Dr. Davis began his counterargument by stating that estimation of absolute vascular risk is an established part of strategies to prevent cardiovascular disease, including in diabetes.
And that risk, he stressed, is actually higher in men.
“Male sex is a consistent adverse risk factor in cardiovascular disease event prediction equations in type 2 diabetes. Identifying absolute risk is important,” he said, noting risk calculators include male sex, such as the risk engine derived from the United Kingdom Prospective Diabetes Trial.
And in the Australian population-based Fremantle study, of which Dr. Davis is an author, the absolute 5-year incidence rates for all outcomes – including myocardial infarction, stroke, heart failure, lower extremity amputation, cardiovascular mortality, and all-cause mortality – were consistently higher in men versus women in the first phase, which began in the 1990s and included 1,426 individuals with diabetes (91% had type 2 diabetes).
In the ongoing second phase, which began in 2008 with 1,732 participants, overall rates of those outcomes are lower and the discrepancy between men and women has narrowed, Dr. Davis noted.
Overall, the Fremantle study data “suggest that women with type 2 diabetes do not need more aggressive cardiovascular reduction than men with type 2 diabetes because they are not at increased absolute vascular risk,” he stressed.
And in a “sensitivity analysis” of two areas in Finland, the authors concluded that the stronger effect of type 2 diabetes on the risk of congenital heart disease (CHD) in women, compared with men was in part explained by a heavier risk factor burden and a greater effect of blood pressure and atherogenic dyslipidemia in women with diabetes, he explained.
The Finnish authors wrote, “In terms of absolute risk of CHD death or a major CHD event, diabetes almost completely abolished the female protection from CHD.”
But, Dr. Davis emphasized, rates were not higher in females.
So then, “why is there the view that women with type 2 diabetes need more aggressive cardiovascular risk reduction than men with diabetes?
“It probably comes back to confusion based on absolute risk versus a comparison of relative risk within each sex,” he asserted.
ADA Standards of Medical Care 2019 don’t mention gender
Lastly, in a meta-analysis published just in July this year involving more than 5 million participants, compared with men with diabetes, women with diabetes had a 58% and 13% greater risk of CHD and all-cause mortality, respectively.
“This points to an urgent need to develop sex- and gender-specific risk assessment strategies and therapeutic interventions that target diabetes management in the context of CHD prevention,” the authors concluded.
But, Dr. Davis noted, “It is not absolute vascular risk. It’s a relative risk compared across the two genders. In the paper, there is no mention of absolute vascular risk.
“Greater CVD mortality in women with and without diabetes, versus men, doesn’t mean there’s also an absolute vascular increase in women versus men with diabetes,” he said.
Moreover, Dr. Davis pointed out that in an editorial accompanying the 2015 meta-analysis in type 1 diabetes, Simmons had actually stated that absolute mortality rates are highest in men.
“I don’t know what happened to his epidemiology knowledge in the last 4 years but it seems to have gone backwards,” he joked to his debate opponent.
And, Dr. Davis asserted, even if there were a higher risk in women with type 1 diabetes, there is no evidence that cardiovascular risk reduction measures affect endpoints in that patient population. Only about 8% of people with diabetes in statin trials had type 1 diabetes.
Indeed, he noted, in the American Diabetes Association Standards of Medical Care in Diabetes – 2019, the treatment goals for individual cardiovascular risk factors do not mention gender.
What’s more, Dr. David said, there is evidence that women are significantly less likely than men to take prescribed statins and are more likely to have an eating disorder and underdose insulin, “suggesting significant issues with compliance. ... So, trying to get more intensive risk reduction in women may be a challenge.”
“Women with diabetes do not need more aggressive cardiovascular risk reduction than men with diabetes, irrespective of type,” he concluded.
A version of this story originally appeared on medscape.com.
BUSAN, SOUTH KOREA – Whether cardiovascular disease risk reduction efforts should be more aggressive in women than men with diabetes depends on how you interpret the data.
Two experts came to different conclusions on this question during a heated, but jovial, debate last week here at the International Diabetes Federation 2019 Congress.
Endocrinologist David Simmons, MB, BChir, Western Sydney University, Campbelltown, Australia, argued that diabetes erases the well-described life expectancy advantage of 4-7 years that women experience over men in the general population.
He also highlighted the fact that the heightened risk is of particular concern in both younger women and those with prior gestational diabetes.
But Timothy Davis, BMedSc, MB, BS, DPhil, an endocrinologist and general physician at Fremantle (Australia) Hospital, countered that the data only show the diabetes-attributable excess cardiovascular risk is higher in women than men, but that the absolute risk is actually greater in men.
Moreover, he argued, at least in type 1 diabetes, there is no evidence that more aggressive cardiovascular risk factor management improves outcomes.
Yes: Diabetes eliminates female CVD protection
Dr. Simmons began by pointing out that, although on average women die at an older age than men, it has been known for over 40 years that this “female protection” is lost in insulin-treated women, particularly as a result of their increased risk for cardiovascular disease.
In a 2015 meta-analysis of 26 studies, women with type 1 diabetes were found to have about a 37% greater risk of all-cause mortality, compared with men with the condition when mortality is contrasted with that of the general population, and twice the risk of both fatal and nonfatal vascular events.
The risk appeared to be greater in women who were younger at the time of diabetes diagnosis. “This is a really important point – the time we would want to intervene,” Dr. Simmons said.
In another meta-analysis of 30 studies including 2,307,694 individuals with type 2 diabetes and 252,491 deaths, the pooled women-to-men ratio of the standardized mortality ratio for all-cause mortality was 1.14.
In those with versus without type 2 diabetes, the pooled standardized mortality ratio in women was 2.30 and in men was 1.94, both significant, compared with those without diabetes.
And in a 2006 meta-analysis of 22 studies involving individuals with type 2 diabetes, the pooled data showed a 46% excess relative risk using standardized mortality ratios in women versus men for fatal coronary artery disease.
Meanwhile, in a 2018 meta-analysis of 68 studies involving nearly 1 million adults examining differences in occlusive vascular disease, after controlling for major vascular risk factors, diabetes roughly doubled the risk for occlusive vascular mortality in men (relative risk, 2.10), but tripled it in women (3.00).
Women with diabetes aged 35-59 years had the highest relative risk for death over follow-up across all age and sex groups: They had 5.5 times the excess risk, compared with those without diabetes, while the excess risk for men of that age was 2.3-fold.
“So very clearly, it’s these young women who are most at risk, “emphasized Dr. Simmons, who is an investigator for Novo Nordisk and a speaker for Medtronic, Novo Nordisk, and Sanofi.
Are disparities because of differences in cvd risk factor management?
The question has arisen whether the female/male differences might be because of differences in cardiovascular risk factor management, Simmons noted.
A 2015 American Heart Association statement laid out the evidence for lower prescribing of statins, aspirin, beta-blockers, and ACE inhibitors in women, compared with men, Dr. Simmons said.
And some studies suggest medication adherence is lower in women than men.
In terms of medications, fenofibrate appears to produce better outcomes in women than men, but there is no evidence of gender differences in the effects of statins, ACE inhibitors, or aspirin, Simmons said.
He also outlined the results of a 2008 study of 78,254 patients with acute myocardial infarction from 420 U.S. hospitals in 2001-2006.
Women were older, had more comorbidities, less often presented with ST-elevation myocardial infarction (STEMI), and had a higher rate of unadjusted in-hospital death (8.2% vs. 5.7%; P less than .0001) than men. Of the participants, 33% of women had diabetes, compared with 28% of men.
The in-hospital mortality difference disappeared after multivariable adjustment, but women with STEMI still had higher adjusted mortality rates than men.
“The underuse of evidence-based treatments and delayed reperfusion in women represent potential opportunities for reducing sex disparities in care and outcome after acute myocardial infarction,” the authors concluded.
“It’s very clear amongst our cardiology colleagues that something needs to be done and that we need more aggressive cardiological risk reduction in women,” Dr. Simmons said.
“The AHA has already decided this. It’s already a policy. So why are we having this debate?” he wondered.
He also pointed out that women with prior gestational diabetes are an exceptionally high–risk group, with a twofold excess risk for cardiovascular disease within the first 10 years post partum.
“We need to do something about this particularly high-risk group, independent of debates about gender,” Dr. Simmons emphasized. “Clearly, women with diabetes warrant more aggressive cardiovascular risk reduction than men with diabetes, especially at those younger ages,” he concluded.
No: Confusion about relative risk within each sex and absolute risk
Dr. Davis began his counterargument by stating that estimation of absolute vascular risk is an established part of strategies to prevent cardiovascular disease, including in diabetes.
And that risk, he stressed, is actually higher in men.
“Male sex is a consistent adverse risk factor in cardiovascular disease event prediction equations in type 2 diabetes. Identifying absolute risk is important,” he said, noting risk calculators include male sex, such as the risk engine derived from the United Kingdom Prospective Diabetes Trial.
And in the Australian population-based Fremantle study, of which Dr. Davis is an author, the absolute 5-year incidence rates for all outcomes – including myocardial infarction, stroke, heart failure, lower extremity amputation, cardiovascular mortality, and all-cause mortality – were consistently higher in men versus women in the first phase, which began in the 1990s and included 1,426 individuals with diabetes (91% had type 2 diabetes).
In the ongoing second phase, which began in 2008 with 1,732 participants, overall rates of those outcomes are lower and the discrepancy between men and women has narrowed, Dr. Davis noted.
Overall, the Fremantle study data “suggest that women with type 2 diabetes do not need more aggressive cardiovascular reduction than men with type 2 diabetes because they are not at increased absolute vascular risk,” he stressed.
And in a “sensitivity analysis” of two areas in Finland, the authors concluded that the stronger effect of type 2 diabetes on the risk of congenital heart disease (CHD) in women, compared with men was in part explained by a heavier risk factor burden and a greater effect of blood pressure and atherogenic dyslipidemia in women with diabetes, he explained.
The Finnish authors wrote, “In terms of absolute risk of CHD death or a major CHD event, diabetes almost completely abolished the female protection from CHD.”
But, Dr. Davis emphasized, rates were not higher in females.
So then, “why is there the view that women with type 2 diabetes need more aggressive cardiovascular risk reduction than men with diabetes?
“It probably comes back to confusion based on absolute risk versus a comparison of relative risk within each sex,” he asserted.
ADA Standards of Medical Care 2019 don’t mention gender
Lastly, in a meta-analysis published just in July this year involving more than 5 million participants, compared with men with diabetes, women with diabetes had a 58% and 13% greater risk of CHD and all-cause mortality, respectively.
“This points to an urgent need to develop sex- and gender-specific risk assessment strategies and therapeutic interventions that target diabetes management in the context of CHD prevention,” the authors concluded.
But, Dr. Davis noted, “It is not absolute vascular risk. It’s a relative risk compared across the two genders. In the paper, there is no mention of absolute vascular risk.
“Greater CVD mortality in women with and without diabetes, versus men, doesn’t mean there’s also an absolute vascular increase in women versus men with diabetes,” he said.
Moreover, Dr. Davis pointed out that in an editorial accompanying the 2015 meta-analysis in type 1 diabetes, Simmons had actually stated that absolute mortality rates are highest in men.
“I don’t know what happened to his epidemiology knowledge in the last 4 years but it seems to have gone backwards,” he joked to his debate opponent.
And, Dr. Davis asserted, even if there were a higher risk in women with type 1 diabetes, there is no evidence that cardiovascular risk reduction measures affect endpoints in that patient population. Only about 8% of people with diabetes in statin trials had type 1 diabetes.
Indeed, he noted, in the American Diabetes Association Standards of Medical Care in Diabetes – 2019, the treatment goals for individual cardiovascular risk factors do not mention gender.
What’s more, Dr. David said, there is evidence that women are significantly less likely than men to take prescribed statins and are more likely to have an eating disorder and underdose insulin, “suggesting significant issues with compliance. ... So, trying to get more intensive risk reduction in women may be a challenge.”
“Women with diabetes do not need more aggressive cardiovascular risk reduction than men with diabetes, irrespective of type,” he concluded.
A version of this story originally appeared on medscape.com.
BUSAN, SOUTH KOREA – Whether cardiovascular disease risk reduction efforts should be more aggressive in women than men with diabetes depends on how you interpret the data.
Two experts came to different conclusions on this question during a heated, but jovial, debate last week here at the International Diabetes Federation 2019 Congress.
Endocrinologist David Simmons, MB, BChir, Western Sydney University, Campbelltown, Australia, argued that diabetes erases the well-described life expectancy advantage of 4-7 years that women experience over men in the general population.
He also highlighted the fact that the heightened risk is of particular concern in both younger women and those with prior gestational diabetes.
But Timothy Davis, BMedSc, MB, BS, DPhil, an endocrinologist and general physician at Fremantle (Australia) Hospital, countered that the data only show the diabetes-attributable excess cardiovascular risk is higher in women than men, but that the absolute risk is actually greater in men.
Moreover, he argued, at least in type 1 diabetes, there is no evidence that more aggressive cardiovascular risk factor management improves outcomes.
Yes: Diabetes eliminates female CVD protection
Dr. Simmons began by pointing out that, although on average women die at an older age than men, it has been known for over 40 years that this “female protection” is lost in insulin-treated women, particularly as a result of their increased risk for cardiovascular disease.
In a 2015 meta-analysis of 26 studies, women with type 1 diabetes were found to have about a 37% greater risk of all-cause mortality, compared with men with the condition when mortality is contrasted with that of the general population, and twice the risk of both fatal and nonfatal vascular events.
The risk appeared to be greater in women who were younger at the time of diabetes diagnosis. “This is a really important point – the time we would want to intervene,” Dr. Simmons said.
In another meta-analysis of 30 studies including 2,307,694 individuals with type 2 diabetes and 252,491 deaths, the pooled women-to-men ratio of the standardized mortality ratio for all-cause mortality was 1.14.
In those with versus without type 2 diabetes, the pooled standardized mortality ratio in women was 2.30 and in men was 1.94, both significant, compared with those without diabetes.
And in a 2006 meta-analysis of 22 studies involving individuals with type 2 diabetes, the pooled data showed a 46% excess relative risk using standardized mortality ratios in women versus men for fatal coronary artery disease.
Meanwhile, in a 2018 meta-analysis of 68 studies involving nearly 1 million adults examining differences in occlusive vascular disease, after controlling for major vascular risk factors, diabetes roughly doubled the risk for occlusive vascular mortality in men (relative risk, 2.10), but tripled it in women (3.00).
Women with diabetes aged 35-59 years had the highest relative risk for death over follow-up across all age and sex groups: They had 5.5 times the excess risk, compared with those without diabetes, while the excess risk for men of that age was 2.3-fold.
“So very clearly, it’s these young women who are most at risk, “emphasized Dr. Simmons, who is an investigator for Novo Nordisk and a speaker for Medtronic, Novo Nordisk, and Sanofi.
Are disparities because of differences in cvd risk factor management?
The question has arisen whether the female/male differences might be because of differences in cardiovascular risk factor management, Simmons noted.
A 2015 American Heart Association statement laid out the evidence for lower prescribing of statins, aspirin, beta-blockers, and ACE inhibitors in women, compared with men, Dr. Simmons said.
And some studies suggest medication adherence is lower in women than men.
In terms of medications, fenofibrate appears to produce better outcomes in women than men, but there is no evidence of gender differences in the effects of statins, ACE inhibitors, or aspirin, Simmons said.
He also outlined the results of a 2008 study of 78,254 patients with acute myocardial infarction from 420 U.S. hospitals in 2001-2006.
Women were older, had more comorbidities, less often presented with ST-elevation myocardial infarction (STEMI), and had a higher rate of unadjusted in-hospital death (8.2% vs. 5.7%; P less than .0001) than men. Of the participants, 33% of women had diabetes, compared with 28% of men.
The in-hospital mortality difference disappeared after multivariable adjustment, but women with STEMI still had higher adjusted mortality rates than men.
“The underuse of evidence-based treatments and delayed reperfusion in women represent potential opportunities for reducing sex disparities in care and outcome after acute myocardial infarction,” the authors concluded.
“It’s very clear amongst our cardiology colleagues that something needs to be done and that we need more aggressive cardiological risk reduction in women,” Dr. Simmons said.
“The AHA has already decided this. It’s already a policy. So why are we having this debate?” he wondered.
He also pointed out that women with prior gestational diabetes are an exceptionally high–risk group, with a twofold excess risk for cardiovascular disease within the first 10 years post partum.
“We need to do something about this particularly high-risk group, independent of debates about gender,” Dr. Simmons emphasized. “Clearly, women with diabetes warrant more aggressive cardiovascular risk reduction than men with diabetes, especially at those younger ages,” he concluded.
No: Confusion about relative risk within each sex and absolute risk
Dr. Davis began his counterargument by stating that estimation of absolute vascular risk is an established part of strategies to prevent cardiovascular disease, including in diabetes.
And that risk, he stressed, is actually higher in men.
“Male sex is a consistent adverse risk factor in cardiovascular disease event prediction equations in type 2 diabetes. Identifying absolute risk is important,” he said, noting risk calculators include male sex, such as the risk engine derived from the United Kingdom Prospective Diabetes Trial.
And in the Australian population-based Fremantle study, of which Dr. Davis is an author, the absolute 5-year incidence rates for all outcomes – including myocardial infarction, stroke, heart failure, lower extremity amputation, cardiovascular mortality, and all-cause mortality – were consistently higher in men versus women in the first phase, which began in the 1990s and included 1,426 individuals with diabetes (91% had type 2 diabetes).
In the ongoing second phase, which began in 2008 with 1,732 participants, overall rates of those outcomes are lower and the discrepancy between men and women has narrowed, Dr. Davis noted.
Overall, the Fremantle study data “suggest that women with type 2 diabetes do not need more aggressive cardiovascular reduction than men with type 2 diabetes because they are not at increased absolute vascular risk,” he stressed.
And in a “sensitivity analysis” of two areas in Finland, the authors concluded that the stronger effect of type 2 diabetes on the risk of congenital heart disease (CHD) in women, compared with men was in part explained by a heavier risk factor burden and a greater effect of blood pressure and atherogenic dyslipidemia in women with diabetes, he explained.
The Finnish authors wrote, “In terms of absolute risk of CHD death or a major CHD event, diabetes almost completely abolished the female protection from CHD.”
But, Dr. Davis emphasized, rates were not higher in females.
So then, “why is there the view that women with type 2 diabetes need more aggressive cardiovascular risk reduction than men with diabetes?
“It probably comes back to confusion based on absolute risk versus a comparison of relative risk within each sex,” he asserted.
ADA Standards of Medical Care 2019 don’t mention gender
Lastly, in a meta-analysis published just in July this year involving more than 5 million participants, compared with men with diabetes, women with diabetes had a 58% and 13% greater risk of CHD and all-cause mortality, respectively.
“This points to an urgent need to develop sex- and gender-specific risk assessment strategies and therapeutic interventions that target diabetes management in the context of CHD prevention,” the authors concluded.
But, Dr. Davis noted, “It is not absolute vascular risk. It’s a relative risk compared across the two genders. In the paper, there is no mention of absolute vascular risk.
“Greater CVD mortality in women with and without diabetes, versus men, doesn’t mean there’s also an absolute vascular increase in women versus men with diabetes,” he said.
Moreover, Dr. Davis pointed out that in an editorial accompanying the 2015 meta-analysis in type 1 diabetes, Simmons had actually stated that absolute mortality rates are highest in men.
“I don’t know what happened to his epidemiology knowledge in the last 4 years but it seems to have gone backwards,” he joked to his debate opponent.
And, Dr. Davis asserted, even if there were a higher risk in women with type 1 diabetes, there is no evidence that cardiovascular risk reduction measures affect endpoints in that patient population. Only about 8% of people with diabetes in statin trials had type 1 diabetes.
Indeed, he noted, in the American Diabetes Association Standards of Medical Care in Diabetes – 2019, the treatment goals for individual cardiovascular risk factors do not mention gender.
What’s more, Dr. David said, there is evidence that women are significantly less likely than men to take prescribed statins and are more likely to have an eating disorder and underdose insulin, “suggesting significant issues with compliance. ... So, trying to get more intensive risk reduction in women may be a challenge.”
“Women with diabetes do not need more aggressive cardiovascular risk reduction than men with diabetes, irrespective of type,” he concluded.
A version of this story originally appeared on medscape.com.
New ASH guideline: VTE prophylaxis after major surgery
ORLANDO – The latest American Society of Hematology guideline on venous thromboembolism (VTE) tackles 30 key questions regarding prophylaxis in hospitalized patients undergoing surgery, according to the chair of the guideline panel, who highlighted 9 of those questions during a special session at the society’s annual meeting.
The clinical practice guideline, published just about a week before the annual meeting of the American Society of Hematology, focuses mainly on pharmacologic prophylaxis in specific surgical settings, said David R. Anderson, MD, dean of the faculty of medicine of Dalhousie University, Halifax, N.S.
“Our guidelines focused upon clinically important symptomatic outcomes, with less emphasis being placed on asymptomatic deep vein thrombosis detected by screening tests,” Dr. Anderson said.
At the special education session, Dr. Anderson highlighted several specific recommendations on prophylaxis in surgical patients.
Pharmacologic prophylaxis is not recommended for patients experiencing major trauma deemed to be at high risk of bleeding. Its use does reduce risk of symptomatic pulmonary embolism (PE) and deep vein thrombosis (DVT) by about 10 events per 1,000 patients treated; however, Dr. Anderson said, the panel’s opinion was that this benefit was outweighed by increased risk of major bleeding, at 24 events per 1,000 patients treated.
“We do recommend, however that this risk of bleeding must be reevaluated over the course of recovery of patients, and this may change the decision around this intervention over time,” Dr. Anderson told attendees at the special session.
That’s because pharmacologic prophylaxis is recommended in surgical patients at low to moderate risk of bleeding. In this scenario, the incremental risk of major bleeding (14 events per 1,000 patients treated) is outweighed by the benefit of the reduction of symptomatic VTE events, according to Dr. Anderson.
When pharmacologic prophylaxis is used, the panel recommends combined prophylaxis – mechanical prophylaxis in addition to pharmacologic prophylaxis – especially in those patients at high or very high risk of VTE. Evidence shows that the combination approach significantly reduces risk of PE, and strongly suggests it may also reduce risk of symptomatic proximal DVT, Dr. Anderson said.
In surgical patients not receiving pharmacologic prophylaxis, mechanical prophylaxis is recommended over no mechanical prophylaxis, he added. Moreover, in those patients receiving mechanical prophylaxis, the ASH panel recommends use of intermittent compression devices over graduated compression stockings.
The panel comes out against prophylactic inferior vena cava (IVC) filter insertion in the guidelines. Dr. Anderson said that the “small reduction” in PE risk seen in observational studies is outweighed by increased risk of DVT, and a resulting trend for increased mortality, associated with insertion of the devices.
“We did not consider other risks of IVC filters such as filter embolization or perforation, which again would be complications that would support our recommendation against routine use of these devices in patients undergoing major surgery,” he said.
In terms of the type of pharmacologic prophylaxis to use, the panel said low-molecular-weight heparin or unfractionated heparin would be reasonable choices in this setting. Available data do not demonstrate any significant differences between these choices for major clinical outcomes, Dr. Anderson added.
The guideline also addresses duration of pharmacologic prophylaxis, stating that extended prophylaxis – of at least 3 weeks – is favored over short-term prophylaxis, or up to 2 weeks of treatment. The extended approach significantly reduces risk of symptomatic PE and proximal DVT, though most of the supporting data come from studies of major joint arthroplasty and major general surgical procedures for patients with cancer. “We need more studies in other clinical areas to examine this particular question,” Dr. Anderson said.
The guideline on prophylaxis in surgical patients was published in Blood Advances (2019 Dec 3;3[23]:3898-944). Six other ASH VTE guidelines, all published in 2018, covered prophylaxis in medical patients, diagnosis, VTE in pregnancy, optimal anticoagulation, heparin-induced thrombocytopenia, and pediatric considerations. The guidelines are available on the ASH website.
Dr. Anderson reported having no relevant conflicts of interest.
ORLANDO – The latest American Society of Hematology guideline on venous thromboembolism (VTE) tackles 30 key questions regarding prophylaxis in hospitalized patients undergoing surgery, according to the chair of the guideline panel, who highlighted 9 of those questions during a special session at the society’s annual meeting.
The clinical practice guideline, published just about a week before the annual meeting of the American Society of Hematology, focuses mainly on pharmacologic prophylaxis in specific surgical settings, said David R. Anderson, MD, dean of the faculty of medicine of Dalhousie University, Halifax, N.S.
“Our guidelines focused upon clinically important symptomatic outcomes, with less emphasis being placed on asymptomatic deep vein thrombosis detected by screening tests,” Dr. Anderson said.
At the special education session, Dr. Anderson highlighted several specific recommendations on prophylaxis in surgical patients.
Pharmacologic prophylaxis is not recommended for patients experiencing major trauma deemed to be at high risk of bleeding. Its use does reduce risk of symptomatic pulmonary embolism (PE) and deep vein thrombosis (DVT) by about 10 events per 1,000 patients treated; however, Dr. Anderson said, the panel’s opinion was that this benefit was outweighed by increased risk of major bleeding, at 24 events per 1,000 patients treated.
“We do recommend, however that this risk of bleeding must be reevaluated over the course of recovery of patients, and this may change the decision around this intervention over time,” Dr. Anderson told attendees at the special session.
That’s because pharmacologic prophylaxis is recommended in surgical patients at low to moderate risk of bleeding. In this scenario, the incremental risk of major bleeding (14 events per 1,000 patients treated) is outweighed by the benefit of the reduction of symptomatic VTE events, according to Dr. Anderson.
When pharmacologic prophylaxis is used, the panel recommends combined prophylaxis – mechanical prophylaxis in addition to pharmacologic prophylaxis – especially in those patients at high or very high risk of VTE. Evidence shows that the combination approach significantly reduces risk of PE, and strongly suggests it may also reduce risk of symptomatic proximal DVT, Dr. Anderson said.
In surgical patients not receiving pharmacologic prophylaxis, mechanical prophylaxis is recommended over no mechanical prophylaxis, he added. Moreover, in those patients receiving mechanical prophylaxis, the ASH panel recommends use of intermittent compression devices over graduated compression stockings.
The panel comes out against prophylactic inferior vena cava (IVC) filter insertion in the guidelines. Dr. Anderson said that the “small reduction” in PE risk seen in observational studies is outweighed by increased risk of DVT, and a resulting trend for increased mortality, associated with insertion of the devices.
“We did not consider other risks of IVC filters such as filter embolization or perforation, which again would be complications that would support our recommendation against routine use of these devices in patients undergoing major surgery,” he said.
In terms of the type of pharmacologic prophylaxis to use, the panel said low-molecular-weight heparin or unfractionated heparin would be reasonable choices in this setting. Available data do not demonstrate any significant differences between these choices for major clinical outcomes, Dr. Anderson added.
The guideline also addresses duration of pharmacologic prophylaxis, stating that extended prophylaxis – of at least 3 weeks – is favored over short-term prophylaxis, or up to 2 weeks of treatment. The extended approach significantly reduces risk of symptomatic PE and proximal DVT, though most of the supporting data come from studies of major joint arthroplasty and major general surgical procedures for patients with cancer. “We need more studies in other clinical areas to examine this particular question,” Dr. Anderson said.
The guideline on prophylaxis in surgical patients was published in Blood Advances (2019 Dec 3;3[23]:3898-944). Six other ASH VTE guidelines, all published in 2018, covered prophylaxis in medical patients, diagnosis, VTE in pregnancy, optimal anticoagulation, heparin-induced thrombocytopenia, and pediatric considerations. The guidelines are available on the ASH website.
Dr. Anderson reported having no relevant conflicts of interest.
ORLANDO – The latest American Society of Hematology guideline on venous thromboembolism (VTE) tackles 30 key questions regarding prophylaxis in hospitalized patients undergoing surgery, according to the chair of the guideline panel, who highlighted 9 of those questions during a special session at the society’s annual meeting.
The clinical practice guideline, published just about a week before the annual meeting of the American Society of Hematology, focuses mainly on pharmacologic prophylaxis in specific surgical settings, said David R. Anderson, MD, dean of the faculty of medicine of Dalhousie University, Halifax, N.S.
“Our guidelines focused upon clinically important symptomatic outcomes, with less emphasis being placed on asymptomatic deep vein thrombosis detected by screening tests,” Dr. Anderson said.
At the special education session, Dr. Anderson highlighted several specific recommendations on prophylaxis in surgical patients.
Pharmacologic prophylaxis is not recommended for patients experiencing major trauma deemed to be at high risk of bleeding. Its use does reduce risk of symptomatic pulmonary embolism (PE) and deep vein thrombosis (DVT) by about 10 events per 1,000 patients treated; however, Dr. Anderson said, the panel’s opinion was that this benefit was outweighed by increased risk of major bleeding, at 24 events per 1,000 patients treated.
“We do recommend, however that this risk of bleeding must be reevaluated over the course of recovery of patients, and this may change the decision around this intervention over time,” Dr. Anderson told attendees at the special session.
That’s because pharmacologic prophylaxis is recommended in surgical patients at low to moderate risk of bleeding. In this scenario, the incremental risk of major bleeding (14 events per 1,000 patients treated) is outweighed by the benefit of the reduction of symptomatic VTE events, according to Dr. Anderson.
When pharmacologic prophylaxis is used, the panel recommends combined prophylaxis – mechanical prophylaxis in addition to pharmacologic prophylaxis – especially in those patients at high or very high risk of VTE. Evidence shows that the combination approach significantly reduces risk of PE, and strongly suggests it may also reduce risk of symptomatic proximal DVT, Dr. Anderson said.
In surgical patients not receiving pharmacologic prophylaxis, mechanical prophylaxis is recommended over no mechanical prophylaxis, he added. Moreover, in those patients receiving mechanical prophylaxis, the ASH panel recommends use of intermittent compression devices over graduated compression stockings.
The panel comes out against prophylactic inferior vena cava (IVC) filter insertion in the guidelines. Dr. Anderson said that the “small reduction” in PE risk seen in observational studies is outweighed by increased risk of DVT, and a resulting trend for increased mortality, associated with insertion of the devices.
“We did not consider other risks of IVC filters such as filter embolization or perforation, which again would be complications that would support our recommendation against routine use of these devices in patients undergoing major surgery,” he said.
In terms of the type of pharmacologic prophylaxis to use, the panel said low-molecular-weight heparin or unfractionated heparin would be reasonable choices in this setting. Available data do not demonstrate any significant differences between these choices for major clinical outcomes, Dr. Anderson added.
The guideline also addresses duration of pharmacologic prophylaxis, stating that extended prophylaxis – of at least 3 weeks – is favored over short-term prophylaxis, or up to 2 weeks of treatment. The extended approach significantly reduces risk of symptomatic PE and proximal DVT, though most of the supporting data come from studies of major joint arthroplasty and major general surgical procedures for patients with cancer. “We need more studies in other clinical areas to examine this particular question,” Dr. Anderson said.
The guideline on prophylaxis in surgical patients was published in Blood Advances (2019 Dec 3;3[23]:3898-944). Six other ASH VTE guidelines, all published in 2018, covered prophylaxis in medical patients, diagnosis, VTE in pregnancy, optimal anticoagulation, heparin-induced thrombocytopenia, and pediatric considerations. The guidelines are available on the ASH website.
Dr. Anderson reported having no relevant conflicts of interest.
EXPERT ANALYSIS FROM ASH 2019
FDA panel rejects vernakalant bid for AFib cardioversion indication
for cardioversion of recent-onset atrial fibrillation (AFib).
It was the second time before an FDA advisory panel for vernakalant (Brinavess, Correvio International Sàrl), which the agency had declined to approve in 2008 due to safety concerns. That time, however, its advisors had given the agency a decidedly positive recommendation.
Since then, registry data collected for the drug’s resubmission seemed only to raise further safety issues, especially evidence that a single infusion may cause severe hypotension and suppress left ventricular function.
Some members of the Cardiovascular and Renal Drugs Advisory Committee (CRDAC), including a number who voted against approval, expressed hopes for further research aimed at identifying specific AFib patient groups who might safely benefit from vernakalant.
Of note, the drug has long been available for AFib cardioversion in Europe, where there are a number of other pharmacologic options, and was recently approved in Canada.
“We do recognize there’s a significant clinical need here,” observed Paul M. Ridker, MD, MPH, of Harvard Medical School and Brigham and Women’s Hospital Boston, a CRDAC panelist.
The results of the safety study that Correvio presented to the panel were “pretty marginal,” Dr. Ridker said. Given the negative safety signals and the available cardioversion alternatives, he questioned whether vernakalant represented a “substantial advance versus just another option. Right now, I’m not convinced it’s a substantial advance.”
FDA representatives were skeptical about vernakalant when they walked into the meeting room, as noted in briefing documents they had circulated beforehand. The drug’s safety experience under consideration included one case of ventricular arrhythmia and cardiogenic shock in a treated patient without apparent structural heart disease, who subsequently died. That case was much discussed throughout the meeting.
In its resubmission of vernakalant to regulators, Correvio also pointed to a significant unmet need for AFib cardioversion options in the United States, given the few alternatives.
For example, ibutilide is FDA-approved for recent-onset AFib or atrial flutter; but as the company and panelists noted, the drug isn’t often used for that indication. Patients with recent-onset AFib are often put on rate-control meds without cardioversion. Or clinicians may resort to electrical cardioversion, which can be logistically cumbersome and require anesthesia and generally a hospital stay.
Oral or intravenous amiodarone and oral dofetilide, flecainide, and propafenone are guideline-recommended but not actually FDA-approved for recent-onset AFib, the company noted.
Correvio made its “pre-infusion checklist” a core feature of its case. It was designed to guide selection of patients for vernakalant cardioversion based on contraindications such as a systolic blood pressure under 100 mm Hg, severe heart failure, aortic stenosis, severe bradycardia or heart block, or a prolonged QT interval.
In his presentation to the panel, FDA medical officer Preston Dunnmon, MD, said the safety results from the SPECTRUM registry, another main pillar of support for the vernakalant resubmission, “are not reassuring.”
As reasons, Dr. Dunnmon cited likely patient-selection bias and its high proportion of patients who were not prospectively enrolled; 21% were retrospectively entered from records.
Moreover, “the proposed preinfusion checklist will not reliably predict which subjects will experience serious cardiovascular adverse events with vernakalant,” he said.
“Vernakalant has induced harm that cannot be reliably predicted, prevented, or in some cases, treated. In contrast to vernakalant, electrical cardioversion and ibutilide pharmacologic cardioversion can cause adverse events, but these are transient and treatable,” he said.
Many on the panel agreed. “I thought the totality of evidence supported the hypothesis that this drug has a potential for a fatal side effect in a disease that you can live with, potentially, and that there are other treatments for,” said Julia B. Lewis, MD, Vanderbilt Medical Center, Nashville, Tenn., who chaired the CRDAC panel.
“The drug clearly converts atrial fibrillation, although it’s only transient,” observed John H. Alexander, MD, MHSc, Duke University, Durham, N.C., one of the two panelists who voted to recommend approval of vernakalant.
“And, there clearly is a serious safety signal in some populations of patients,” he agreed. “However, I was more reassured by the SPECTRUM data.” There is likely to be a low-risk group of patients for whom vernakalant could represent an important option that “outweighs the relatively low risk of serious complications,” Dr. Alexander said.
“So more work needs to be done to clarify who are the low risk patients where it would be favorable.”
Panelist Matthew Needleman, MD, Walter Reed National Military Medical Center, Bethesda, Md., also voted in favor of approval.
“We’ve all known patients with normal ejection fractions who keep coming in with symptomatic atrial fib, want to get out of it quickly, and get back to their lives. So having an option like this I think would be good for a very select group of patients,” Dr. Needleman said.
But the preinfusion checklist and other potential ways to select low-risk patients for vernakalant could potentially backfire, warned John M. Mandrola, MD, Baptist Medical Associates, Louisville, Ky., from the panel.
The FDA representatives had presented evidence that the drug can seriously depress ventricular function, and that the lower cardiac output is what leads to hypotension, he elaborated in an interview after the meeting.
If the checklist is used to exclude hemodynamically unstable patients from receiving vernakalant, he said, “Then you’re really giving this drug to relatively healthy patients for convenience, to decrease hospitalization or the hospital stay.”
The signal for substantial harm, Dr. Mandrola said, has to be balanced against that modest benefit.
Moreover, those in whom the drug doesn’t work may be left in a worse situation, he proposed. Only about half of patients are successfully converted on vernakalant, the company and FDA data suggested. The other half of patients who don’t achieve sinus rhythm on the drug still must face the significant hazards of depressed ejection fraction and hypotension, a high price to pay for an unsuccessful treatment.
Dr. Mandrola is Chief Cardiology Correspondent for theheart.org | Medscape Cardiology; his disclosure statement states no relevant financial relationships.
This article first appeared on Medscape.com.
for cardioversion of recent-onset atrial fibrillation (AFib).
It was the second time before an FDA advisory panel for vernakalant (Brinavess, Correvio International Sàrl), which the agency had declined to approve in 2008 due to safety concerns. That time, however, its advisors had given the agency a decidedly positive recommendation.
Since then, registry data collected for the drug’s resubmission seemed only to raise further safety issues, especially evidence that a single infusion may cause severe hypotension and suppress left ventricular function.
Some members of the Cardiovascular and Renal Drugs Advisory Committee (CRDAC), including a number who voted against approval, expressed hopes for further research aimed at identifying specific AFib patient groups who might safely benefit from vernakalant.
Of note, the drug has long been available for AFib cardioversion in Europe, where there are a number of other pharmacologic options, and was recently approved in Canada.
“We do recognize there’s a significant clinical need here,” observed Paul M. Ridker, MD, MPH, of Harvard Medical School and Brigham and Women’s Hospital Boston, a CRDAC panelist.
The results of the safety study that Correvio presented to the panel were “pretty marginal,” Dr. Ridker said. Given the negative safety signals and the available cardioversion alternatives, he questioned whether vernakalant represented a “substantial advance versus just another option. Right now, I’m not convinced it’s a substantial advance.”
FDA representatives were skeptical about vernakalant when they walked into the meeting room, as noted in briefing documents they had circulated beforehand. The drug’s safety experience under consideration included one case of ventricular arrhythmia and cardiogenic shock in a treated patient without apparent structural heart disease, who subsequently died. That case was much discussed throughout the meeting.
In its resubmission of vernakalant to regulators, Correvio also pointed to a significant unmet need for AFib cardioversion options in the United States, given the few alternatives.
For example, ibutilide is FDA-approved for recent-onset AFib or atrial flutter; but as the company and panelists noted, the drug isn’t often used for that indication. Patients with recent-onset AFib are often put on rate-control meds without cardioversion. Or clinicians may resort to electrical cardioversion, which can be logistically cumbersome and require anesthesia and generally a hospital stay.
Oral or intravenous amiodarone and oral dofetilide, flecainide, and propafenone are guideline-recommended but not actually FDA-approved for recent-onset AFib, the company noted.
Correvio made its “pre-infusion checklist” a core feature of its case. It was designed to guide selection of patients for vernakalant cardioversion based on contraindications such as a systolic blood pressure under 100 mm Hg, severe heart failure, aortic stenosis, severe bradycardia or heart block, or a prolonged QT interval.
In his presentation to the panel, FDA medical officer Preston Dunnmon, MD, said the safety results from the SPECTRUM registry, another main pillar of support for the vernakalant resubmission, “are not reassuring.”
As reasons, Dr. Dunnmon cited likely patient-selection bias and its high proportion of patients who were not prospectively enrolled; 21% were retrospectively entered from records.
Moreover, “the proposed preinfusion checklist will not reliably predict which subjects will experience serious cardiovascular adverse events with vernakalant,” he said.
“Vernakalant has induced harm that cannot be reliably predicted, prevented, or in some cases, treated. In contrast to vernakalant, electrical cardioversion and ibutilide pharmacologic cardioversion can cause adverse events, but these are transient and treatable,” he said.
Many on the panel agreed. “I thought the totality of evidence supported the hypothesis that this drug has a potential for a fatal side effect in a disease that you can live with, potentially, and that there are other treatments for,” said Julia B. Lewis, MD, Vanderbilt Medical Center, Nashville, Tenn., who chaired the CRDAC panel.
“The drug clearly converts atrial fibrillation, although it’s only transient,” observed John H. Alexander, MD, MHSc, Duke University, Durham, N.C., one of the two panelists who voted to recommend approval of vernakalant.
“And, there clearly is a serious safety signal in some populations of patients,” he agreed. “However, I was more reassured by the SPECTRUM data.” There is likely to be a low-risk group of patients for whom vernakalant could represent an important option that “outweighs the relatively low risk of serious complications,” Dr. Alexander said.
“So more work needs to be done to clarify who are the low risk patients where it would be favorable.”
Panelist Matthew Needleman, MD, Walter Reed National Military Medical Center, Bethesda, Md., also voted in favor of approval.
“We’ve all known patients with normal ejection fractions who keep coming in with symptomatic atrial fib, want to get out of it quickly, and get back to their lives. So having an option like this I think would be good for a very select group of patients,” Dr. Needleman said.
But the preinfusion checklist and other potential ways to select low-risk patients for vernakalant could potentially backfire, warned John M. Mandrola, MD, Baptist Medical Associates, Louisville, Ky., from the panel.
The FDA representatives had presented evidence that the drug can seriously depress ventricular function, and that the lower cardiac output is what leads to hypotension, he elaborated in an interview after the meeting.
If the checklist is used to exclude hemodynamically unstable patients from receiving vernakalant, he said, “Then you’re really giving this drug to relatively healthy patients for convenience, to decrease hospitalization or the hospital stay.”
The signal for substantial harm, Dr. Mandrola said, has to be balanced against that modest benefit.
Moreover, those in whom the drug doesn’t work may be left in a worse situation, he proposed. Only about half of patients are successfully converted on vernakalant, the company and FDA data suggested. The other half of patients who don’t achieve sinus rhythm on the drug still must face the significant hazards of depressed ejection fraction and hypotension, a high price to pay for an unsuccessful treatment.
Dr. Mandrola is Chief Cardiology Correspondent for theheart.org | Medscape Cardiology; his disclosure statement states no relevant financial relationships.
This article first appeared on Medscape.com.
for cardioversion of recent-onset atrial fibrillation (AFib).
It was the second time before an FDA advisory panel for vernakalant (Brinavess, Correvio International Sàrl), which the agency had declined to approve in 2008 due to safety concerns. That time, however, its advisors had given the agency a decidedly positive recommendation.
Since then, registry data collected for the drug’s resubmission seemed only to raise further safety issues, especially evidence that a single infusion may cause severe hypotension and suppress left ventricular function.
Some members of the Cardiovascular and Renal Drugs Advisory Committee (CRDAC), including a number who voted against approval, expressed hopes for further research aimed at identifying specific AFib patient groups who might safely benefit from vernakalant.
Of note, the drug has long been available for AFib cardioversion in Europe, where there are a number of other pharmacologic options, and was recently approved in Canada.
“We do recognize there’s a significant clinical need here,” observed Paul M. Ridker, MD, MPH, of Harvard Medical School and Brigham and Women’s Hospital Boston, a CRDAC panelist.
The results of the safety study that Correvio presented to the panel were “pretty marginal,” Dr. Ridker said. Given the negative safety signals and the available cardioversion alternatives, he questioned whether vernakalant represented a “substantial advance versus just another option. Right now, I’m not convinced it’s a substantial advance.”
FDA representatives were skeptical about vernakalant when they walked into the meeting room, as noted in briefing documents they had circulated beforehand. The drug’s safety experience under consideration included one case of ventricular arrhythmia and cardiogenic shock in a treated patient without apparent structural heart disease, who subsequently died. That case was much discussed throughout the meeting.
In its resubmission of vernakalant to regulators, Correvio also pointed to a significant unmet need for AFib cardioversion options in the United States, given the few alternatives.
For example, ibutilide is FDA-approved for recent-onset AFib or atrial flutter; but as the company and panelists noted, the drug isn’t often used for that indication. Patients with recent-onset AFib are often put on rate-control meds without cardioversion. Or clinicians may resort to electrical cardioversion, which can be logistically cumbersome and require anesthesia and generally a hospital stay.
Oral or intravenous amiodarone and oral dofetilide, flecainide, and propafenone are guideline-recommended but not actually FDA-approved for recent-onset AFib, the company noted.
Correvio made its “pre-infusion checklist” a core feature of its case. It was designed to guide selection of patients for vernakalant cardioversion based on contraindications such as a systolic blood pressure under 100 mm Hg, severe heart failure, aortic stenosis, severe bradycardia or heart block, or a prolonged QT interval.
In his presentation to the panel, FDA medical officer Preston Dunnmon, MD, said the safety results from the SPECTRUM registry, another main pillar of support for the vernakalant resubmission, “are not reassuring.”
As reasons, Dr. Dunnmon cited likely patient-selection bias and its high proportion of patients who were not prospectively enrolled; 21% were retrospectively entered from records.
Moreover, “the proposed preinfusion checklist will not reliably predict which subjects will experience serious cardiovascular adverse events with vernakalant,” he said.
“Vernakalant has induced harm that cannot be reliably predicted, prevented, or in some cases, treated. In contrast to vernakalant, electrical cardioversion and ibutilide pharmacologic cardioversion can cause adverse events, but these are transient and treatable,” he said.
Many on the panel agreed. “I thought the totality of evidence supported the hypothesis that this drug has a potential for a fatal side effect in a disease that you can live with, potentially, and that there are other treatments for,” said Julia B. Lewis, MD, Vanderbilt Medical Center, Nashville, Tenn., who chaired the CRDAC panel.
“The drug clearly converts atrial fibrillation, although it’s only transient,” observed John H. Alexander, MD, MHSc, Duke University, Durham, N.C., one of the two panelists who voted to recommend approval of vernakalant.
“And, there clearly is a serious safety signal in some populations of patients,” he agreed. “However, I was more reassured by the SPECTRUM data.” There is likely to be a low-risk group of patients for whom vernakalant could represent an important option that “outweighs the relatively low risk of serious complications,” Dr. Alexander said.
“So more work needs to be done to clarify who are the low risk patients where it would be favorable.”
Panelist Matthew Needleman, MD, Walter Reed National Military Medical Center, Bethesda, Md., also voted in favor of approval.
“We’ve all known patients with normal ejection fractions who keep coming in with symptomatic atrial fib, want to get out of it quickly, and get back to their lives. So having an option like this I think would be good for a very select group of patients,” Dr. Needleman said.
But the preinfusion checklist and other potential ways to select low-risk patients for vernakalant could potentially backfire, warned John M. Mandrola, MD, Baptist Medical Associates, Louisville, Ky., from the panel.
The FDA representatives had presented evidence that the drug can seriously depress ventricular function, and that the lower cardiac output is what leads to hypotension, he elaborated in an interview after the meeting.
If the checklist is used to exclude hemodynamically unstable patients from receiving vernakalant, he said, “Then you’re really giving this drug to relatively healthy patients for convenience, to decrease hospitalization or the hospital stay.”
The signal for substantial harm, Dr. Mandrola said, has to be balanced against that modest benefit.
Moreover, those in whom the drug doesn’t work may be left in a worse situation, he proposed. Only about half of patients are successfully converted on vernakalant, the company and FDA data suggested. The other half of patients who don’t achieve sinus rhythm on the drug still must face the significant hazards of depressed ejection fraction and hypotension, a high price to pay for an unsuccessful treatment.
Dr. Mandrola is Chief Cardiology Correspondent for theheart.org | Medscape Cardiology; his disclosure statement states no relevant financial relationships.
This article first appeared on Medscape.com.
Cardiac arrhythmia heightens mortality risk during epilepsy hospitalizations
BALTIMORE – Patients hospitalized for epilepsy may have higher odds of death if they have a secondary diagnosis of arrhythmia, whereas the presence of apnea alone may not significantly increase mortality, according to an analysis of data from the Nationwide Inpatient Sample presented at the annual meeting of the American Epilepsy Society.
“If you have someone with arrhythmia and epilepsy, you have to be more concerned about possible SUDEP [sudden unexpected death in epilepsy],” relative to someone with apnea and epilepsy, said senior study author Sanjay P. Singh, MD, professor of neurology at Creighton University, Omaha, Neb.
Research indicates that apnea and cardiac arrhythmias may contribute to SUDEP, and the incidence of SUDEP is higher in patients with intractable epilepsy.
To identify the prevalence of apnea, arrhythmia, and both conditions in epilepsy hospitalizations, as well as the prevalence of intractable epilepsy and mortality, Dr. Singh and colleagues performed a retrospective, cross-sectional analysis of pediatric and adult epilepsy hospitalizations between 2003 and 2014 in the Nationwide Inpatient Sample. They determined apnea and arrhythmia diagnoses using ICD-9-CM codes.
Among more than 2.6 million epilepsy hospitalizations, the prevalence of apnea was 2.75%, the prevalence of arrhythmia was 8.91%, and the prevalence of both was 0.49%. The proportion of patients with intractable epilepsy was 7.7%. Among the more than 207,000 hospitalizations with intractable epilepsy, the prevalence of apnea was 3.62%, the prevalence of arrhythmia was 3.34%, and the prevalence of both was 0.36%. The prevalence trend of apnea, arrhythmia, and both together increased between 2003 and 2014.
“In univariate analysis, prevalence of mortality was highest among patients with arrhythmia,” the researchers reported, at – 3.1% in patients with arrhythmia versus 0.48% in patients with apnea, 2.91% in patients with both, and 0.46% in patients without apnea or arrhythmia.
In a multivariable regression analysis, significant and independent predictors of death included intractable epilepsy (odds ratio, 1.17), apnea (OR, 0.84), arrhythmia (OR, 3.29), and the presence of both apnea and arrhythmia (OR, 3.24). When hospitalization was complicated by intractable epilepsy, the odds of death rose with the presence of apnea (OR, 2.07), arrhythmia (OR, 8.39), and with both apnea and arrhythmia (OR, 11.64).
The results highlight the importance of effective epilepsy management, said first author Urvish K. Patel, MBBS, also with Creighton University. “If we can stop [conversion to intractable epilepsy], then this odds ratio can go down.”
Attention to arrhythmias, as well as the combination of arrhythmias and apnea, may “be important in identifying patients at risk for SUDEP,” the authors concluded.
The researchers had no disclosures and reported receiving no outside funding for their work.
SOURCE: Patel UK et al. AES 2019, Abstract 2.140.
BALTIMORE – Patients hospitalized for epilepsy may have higher odds of death if they have a secondary diagnosis of arrhythmia, whereas the presence of apnea alone may not significantly increase mortality, according to an analysis of data from the Nationwide Inpatient Sample presented at the annual meeting of the American Epilepsy Society.
“If you have someone with arrhythmia and epilepsy, you have to be more concerned about possible SUDEP [sudden unexpected death in epilepsy],” relative to someone with apnea and epilepsy, said senior study author Sanjay P. Singh, MD, professor of neurology at Creighton University, Omaha, Neb.
Research indicates that apnea and cardiac arrhythmias may contribute to SUDEP, and the incidence of SUDEP is higher in patients with intractable epilepsy.
To identify the prevalence of apnea, arrhythmia, and both conditions in epilepsy hospitalizations, as well as the prevalence of intractable epilepsy and mortality, Dr. Singh and colleagues performed a retrospective, cross-sectional analysis of pediatric and adult epilepsy hospitalizations between 2003 and 2014 in the Nationwide Inpatient Sample. They determined apnea and arrhythmia diagnoses using ICD-9-CM codes.
Among more than 2.6 million epilepsy hospitalizations, the prevalence of apnea was 2.75%, the prevalence of arrhythmia was 8.91%, and the prevalence of both was 0.49%. The proportion of patients with intractable epilepsy was 7.7%. Among the more than 207,000 hospitalizations with intractable epilepsy, the prevalence of apnea was 3.62%, the prevalence of arrhythmia was 3.34%, and the prevalence of both was 0.36%. The prevalence trend of apnea, arrhythmia, and both together increased between 2003 and 2014.
“In univariate analysis, prevalence of mortality was highest among patients with arrhythmia,” the researchers reported, at – 3.1% in patients with arrhythmia versus 0.48% in patients with apnea, 2.91% in patients with both, and 0.46% in patients without apnea or arrhythmia.
In a multivariable regression analysis, significant and independent predictors of death included intractable epilepsy (odds ratio, 1.17), apnea (OR, 0.84), arrhythmia (OR, 3.29), and the presence of both apnea and arrhythmia (OR, 3.24). When hospitalization was complicated by intractable epilepsy, the odds of death rose with the presence of apnea (OR, 2.07), arrhythmia (OR, 8.39), and with both apnea and arrhythmia (OR, 11.64).
The results highlight the importance of effective epilepsy management, said first author Urvish K. Patel, MBBS, also with Creighton University. “If we can stop [conversion to intractable epilepsy], then this odds ratio can go down.”
Attention to arrhythmias, as well as the combination of arrhythmias and apnea, may “be important in identifying patients at risk for SUDEP,” the authors concluded.
The researchers had no disclosures and reported receiving no outside funding for their work.
SOURCE: Patel UK et al. AES 2019, Abstract 2.140.
BALTIMORE – Patients hospitalized for epilepsy may have higher odds of death if they have a secondary diagnosis of arrhythmia, whereas the presence of apnea alone may not significantly increase mortality, according to an analysis of data from the Nationwide Inpatient Sample presented at the annual meeting of the American Epilepsy Society.
“If you have someone with arrhythmia and epilepsy, you have to be more concerned about possible SUDEP [sudden unexpected death in epilepsy],” relative to someone with apnea and epilepsy, said senior study author Sanjay P. Singh, MD, professor of neurology at Creighton University, Omaha, Neb.
Research indicates that apnea and cardiac arrhythmias may contribute to SUDEP, and the incidence of SUDEP is higher in patients with intractable epilepsy.
To identify the prevalence of apnea, arrhythmia, and both conditions in epilepsy hospitalizations, as well as the prevalence of intractable epilepsy and mortality, Dr. Singh and colleagues performed a retrospective, cross-sectional analysis of pediatric and adult epilepsy hospitalizations between 2003 and 2014 in the Nationwide Inpatient Sample. They determined apnea and arrhythmia diagnoses using ICD-9-CM codes.
Among more than 2.6 million epilepsy hospitalizations, the prevalence of apnea was 2.75%, the prevalence of arrhythmia was 8.91%, and the prevalence of both was 0.49%. The proportion of patients with intractable epilepsy was 7.7%. Among the more than 207,000 hospitalizations with intractable epilepsy, the prevalence of apnea was 3.62%, the prevalence of arrhythmia was 3.34%, and the prevalence of both was 0.36%. The prevalence trend of apnea, arrhythmia, and both together increased between 2003 and 2014.
“In univariate analysis, prevalence of mortality was highest among patients with arrhythmia,” the researchers reported, at – 3.1% in patients with arrhythmia versus 0.48% in patients with apnea, 2.91% in patients with both, and 0.46% in patients without apnea or arrhythmia.
In a multivariable regression analysis, significant and independent predictors of death included intractable epilepsy (odds ratio, 1.17), apnea (OR, 0.84), arrhythmia (OR, 3.29), and the presence of both apnea and arrhythmia (OR, 3.24). When hospitalization was complicated by intractable epilepsy, the odds of death rose with the presence of apnea (OR, 2.07), arrhythmia (OR, 8.39), and with both apnea and arrhythmia (OR, 11.64).
The results highlight the importance of effective epilepsy management, said first author Urvish K. Patel, MBBS, also with Creighton University. “If we can stop [conversion to intractable epilepsy], then this odds ratio can go down.”
Attention to arrhythmias, as well as the combination of arrhythmias and apnea, may “be important in identifying patients at risk for SUDEP,” the authors concluded.
The researchers had no disclosures and reported receiving no outside funding for their work.
SOURCE: Patel UK et al. AES 2019, Abstract 2.140.
REPORTING FROM AES 2019
Health benefits of TAVR over SAVR sustained at 1 year
SAN FRANCISCO – Among patients with severe aortic stenosis at low surgical risk, both transcatheter and surgical aortic valve replacement resulted in substantial health status benefits at 1 year despite most patients having New York Heart Association class I or II symptoms at baseline.
However, when compared with surgical replacement,
The findings come from an analysis of patients enrolled in the randomized PARTNER 3 trial, which showed that transcatheter aortic valve replacement (TAVR) with the SAPIEN 3 valve. At 1 year post procedure, the rate of the primary composite endpoint comprising death, stroke, or cardiovascular rehospitalization was 8.5% in the TAVR group and 15.1% with surgical aortic valve replacement (SAVR), for a highly significant 46% relative risk reduction (N Engl J Med 2019 May 2;380:1695-705).
“The PARTNER 3 and Evolut Low Risk trials have demonstrated that transfemoral TAVR is both safe and effective when compared with SAVR in patients with severe aortic stenosis at low surgical risk,” Suzanne J. Baron, MD, MSc, said at the Transcatheter Cardiovascular Therapeutics annual meeting. “While prior studies have demonstrated improved early health status with transfemoral TAVR, compared with SAVR in intermediate and high-risk patients, there is little evidence of any late health status benefit with TAVR.”
To address this gap in knowledge, Dr. Baron, director of interventional cardiology research at Lahey Hospital and Medical Center in Burlington, Mass., and associates performed a prospective study alongside the PARTNER 3 randomized trial to understand the impact of valve replacement strategy on early and late health status in aortic stenosis patients at low surgical risk. She reported results from 449 low-risk patients with severe aortic stenosis who were assigned to transfemoral TAVR using a balloon-expandable valve, and 449 who were assigned to surgery in PARTNER 3. At baseline, the mean age of patients was 73 years, 69% were male, and the average STS (Society of Thoracic Surgeons) Risk Score was 1.9%. Rates of other comorbidities were generally low.
Patients in both groups reported a mild baseline impairment in health status. The mean Kansas City Cardiomyopathy Questionnaire–Overall Summary (KCCQ-OS) score was 70, “which corresponds to only New York Heart Association Class II symptoms,” Dr. Baron said. “The SF-36 [Short Form 36] physical summary score was 44 for both groups, which is approximately half of a standard deviation below the population mean.”
As expected, patients who underwent TAVR showed substantially improved health status at 1 month based on the KCCQ-OS (mean difference,16 points; P less than .001). However, in contrast to prior studies, the researchers observed a persistent, although attenuated, benefit of TAVR over SAVR in disease-specific health status at 6 and 12 months (mean difference in KCCQ-OS of 2.6 and 1.8 points respectively; P less than .04 for both).
Dr. Baron said that a sustained benefit of TAVR over SAVR at 6 months and 1 year was observed on several KCCQ subscales, but a similar benefit was not noted on the generic health status measures such as the SF-36 physical summary score. “That’s likely reflective of the fact that, as a disease-specific measure, the KCCQ is much more sensitive in detecting meaningful differences in this population,” she explained. When change in health status was analyzed as an ordinal variable, with death as the worst outcome and large clinical improvement, which was defined as a 20-point or greater increase in the KCCQ-OS score, TAVR showed a significant benefit, compared with surgery at all time points (P less than .05).
In an effort to better understand the mechanism underlying this persistent albeit small late benefit in disease-specific health status with TAVR, the researchers generated cumulative distribution curves to display the proportion of patients who achieved a given change on the KCCQ-OS. A clear separation of the curves emerged, with 5.2% more patients in the TAVR group experiencing a change of at least 20 points, compared with the surgery group. “This suggests that the difference in late health status between the two groups is driven by this 5.2% absolute risk difference in the proportion of patients who experienced a large clinical improvement,” Dr. Baron said at the meeting, which was sponsored by the Cardiovascular Research Foundation.
Next, the researchers performed subgroup analyses to examine the interaction between the 1-year health status benefit of TAVR over surgery and prespecified baseline characteristics including age, gender, STS risk score, ejection fraction, atrial fibrillation, and New York Heart Association (NYHA) class. They observed a significant interaction between NYHA class and treatment effect such that patients who had NYHA class III or IV symptoms at baseline derived greater benefit from TAVR, compared with those who had NYHA class I or II symptoms at baseline.
“This finding suggests that it’s the patients with worse functional impairment at baseline who may be that subset of patients on the cumulative responder curves who gained better health status outcomes with TAVR, compared with surgery in the low-risk population,” Dr. Baron said.
Suzanne V. Arnold, MD, a cardiologist at Saint Luke’s Mid America Heart Institute, Kansas City, Mo., who was an invited discussant, said that it was “remarkable” that patients in the substudy were not particularly symptomatic and yet they still experienced close to a 20-point improvement in the KCCQ-OS score following TAVR, and asked whether frailty may have played a role in the 1.8-point adjusted difference in the KCCQ-OS score between TAVR and surgery at 1 year. Dr. Baron responded that she and her colleagues performed a subgroup analysis of patients who had two or more markers of frailty versus those who had one or less. Noting that there were only 20 patients in that subgroup, she said there was a significant signal that patients who were considered have two or more frail measures were considered to do much better with TAVR.
Dr. Baron concluded that the study’s overall findings, taken together with the clinical outcomes of the PARTNER 3 trial, “further support the use of TAVR in patients with severe [aortic stenosis] at low surgical risk. Longer-term follow up is needed (and ongoing) to determine whether the health status benefits of TAVR at 1 year are durable.”
The content of the study was published online at the time of presentation (J Am Coll Cardiol 2019 Sep 29. doi: 10.1016/j.jacc.2019.09.007). The PARTNER 3 quality of life substudy was funded by Edwards Lifesciences. Dr. Baron disclosed research funding and advisory board compensation from Boston Scientific Corp and consulting fees from Edwards Lifesciences.
SAN FRANCISCO – Among patients with severe aortic stenosis at low surgical risk, both transcatheter and surgical aortic valve replacement resulted in substantial health status benefits at 1 year despite most patients having New York Heart Association class I or II symptoms at baseline.
However, when compared with surgical replacement,
The findings come from an analysis of patients enrolled in the randomized PARTNER 3 trial, which showed that transcatheter aortic valve replacement (TAVR) with the SAPIEN 3 valve. At 1 year post procedure, the rate of the primary composite endpoint comprising death, stroke, or cardiovascular rehospitalization was 8.5% in the TAVR group and 15.1% with surgical aortic valve replacement (SAVR), for a highly significant 46% relative risk reduction (N Engl J Med 2019 May 2;380:1695-705).
“The PARTNER 3 and Evolut Low Risk trials have demonstrated that transfemoral TAVR is both safe and effective when compared with SAVR in patients with severe aortic stenosis at low surgical risk,” Suzanne J. Baron, MD, MSc, said at the Transcatheter Cardiovascular Therapeutics annual meeting. “While prior studies have demonstrated improved early health status with transfemoral TAVR, compared with SAVR in intermediate and high-risk patients, there is little evidence of any late health status benefit with TAVR.”
To address this gap in knowledge, Dr. Baron, director of interventional cardiology research at Lahey Hospital and Medical Center in Burlington, Mass., and associates performed a prospective study alongside the PARTNER 3 randomized trial to understand the impact of valve replacement strategy on early and late health status in aortic stenosis patients at low surgical risk. She reported results from 449 low-risk patients with severe aortic stenosis who were assigned to transfemoral TAVR using a balloon-expandable valve, and 449 who were assigned to surgery in PARTNER 3. At baseline, the mean age of patients was 73 years, 69% were male, and the average STS (Society of Thoracic Surgeons) Risk Score was 1.9%. Rates of other comorbidities were generally low.
Patients in both groups reported a mild baseline impairment in health status. The mean Kansas City Cardiomyopathy Questionnaire–Overall Summary (KCCQ-OS) score was 70, “which corresponds to only New York Heart Association Class II symptoms,” Dr. Baron said. “The SF-36 [Short Form 36] physical summary score was 44 for both groups, which is approximately half of a standard deviation below the population mean.”
As expected, patients who underwent TAVR showed substantially improved health status at 1 month based on the KCCQ-OS (mean difference,16 points; P less than .001). However, in contrast to prior studies, the researchers observed a persistent, although attenuated, benefit of TAVR over SAVR in disease-specific health status at 6 and 12 months (mean difference in KCCQ-OS of 2.6 and 1.8 points respectively; P less than .04 for both).
Dr. Baron said that a sustained benefit of TAVR over SAVR at 6 months and 1 year was observed on several KCCQ subscales, but a similar benefit was not noted on the generic health status measures such as the SF-36 physical summary score. “That’s likely reflective of the fact that, as a disease-specific measure, the KCCQ is much more sensitive in detecting meaningful differences in this population,” she explained. When change in health status was analyzed as an ordinal variable, with death as the worst outcome and large clinical improvement, which was defined as a 20-point or greater increase in the KCCQ-OS score, TAVR showed a significant benefit, compared with surgery at all time points (P less than .05).
In an effort to better understand the mechanism underlying this persistent albeit small late benefit in disease-specific health status with TAVR, the researchers generated cumulative distribution curves to display the proportion of patients who achieved a given change on the KCCQ-OS. A clear separation of the curves emerged, with 5.2% more patients in the TAVR group experiencing a change of at least 20 points, compared with the surgery group. “This suggests that the difference in late health status between the two groups is driven by this 5.2% absolute risk difference in the proportion of patients who experienced a large clinical improvement,” Dr. Baron said at the meeting, which was sponsored by the Cardiovascular Research Foundation.
Next, the researchers performed subgroup analyses to examine the interaction between the 1-year health status benefit of TAVR over surgery and prespecified baseline characteristics including age, gender, STS risk score, ejection fraction, atrial fibrillation, and New York Heart Association (NYHA) class. They observed a significant interaction between NYHA class and treatment effect such that patients who had NYHA class III or IV symptoms at baseline derived greater benefit from TAVR, compared with those who had NYHA class I or II symptoms at baseline.
“This finding suggests that it’s the patients with worse functional impairment at baseline who may be that subset of patients on the cumulative responder curves who gained better health status outcomes with TAVR, compared with surgery in the low-risk population,” Dr. Baron said.
Suzanne V. Arnold, MD, a cardiologist at Saint Luke’s Mid America Heart Institute, Kansas City, Mo., who was an invited discussant, said that it was “remarkable” that patients in the substudy were not particularly symptomatic and yet they still experienced close to a 20-point improvement in the KCCQ-OS score following TAVR, and asked whether frailty may have played a role in the 1.8-point adjusted difference in the KCCQ-OS score between TAVR and surgery at 1 year. Dr. Baron responded that she and her colleagues performed a subgroup analysis of patients who had two or more markers of frailty versus those who had one or less. Noting that there were only 20 patients in that subgroup, she said there was a significant signal that patients who were considered have two or more frail measures were considered to do much better with TAVR.
Dr. Baron concluded that the study’s overall findings, taken together with the clinical outcomes of the PARTNER 3 trial, “further support the use of TAVR in patients with severe [aortic stenosis] at low surgical risk. Longer-term follow up is needed (and ongoing) to determine whether the health status benefits of TAVR at 1 year are durable.”
The content of the study was published online at the time of presentation (J Am Coll Cardiol 2019 Sep 29. doi: 10.1016/j.jacc.2019.09.007). The PARTNER 3 quality of life substudy was funded by Edwards Lifesciences. Dr. Baron disclosed research funding and advisory board compensation from Boston Scientific Corp and consulting fees from Edwards Lifesciences.
SAN FRANCISCO – Among patients with severe aortic stenosis at low surgical risk, both transcatheter and surgical aortic valve replacement resulted in substantial health status benefits at 1 year despite most patients having New York Heart Association class I or II symptoms at baseline.
However, when compared with surgical replacement,
The findings come from an analysis of patients enrolled in the randomized PARTNER 3 trial, which showed that transcatheter aortic valve replacement (TAVR) with the SAPIEN 3 valve. At 1 year post procedure, the rate of the primary composite endpoint comprising death, stroke, or cardiovascular rehospitalization was 8.5% in the TAVR group and 15.1% with surgical aortic valve replacement (SAVR), for a highly significant 46% relative risk reduction (N Engl J Med 2019 May 2;380:1695-705).
“The PARTNER 3 and Evolut Low Risk trials have demonstrated that transfemoral TAVR is both safe and effective when compared with SAVR in patients with severe aortic stenosis at low surgical risk,” Suzanne J. Baron, MD, MSc, said at the Transcatheter Cardiovascular Therapeutics annual meeting. “While prior studies have demonstrated improved early health status with transfemoral TAVR, compared with SAVR in intermediate and high-risk patients, there is little evidence of any late health status benefit with TAVR.”
To address this gap in knowledge, Dr. Baron, director of interventional cardiology research at Lahey Hospital and Medical Center in Burlington, Mass., and associates performed a prospective study alongside the PARTNER 3 randomized trial to understand the impact of valve replacement strategy on early and late health status in aortic stenosis patients at low surgical risk. She reported results from 449 low-risk patients with severe aortic stenosis who were assigned to transfemoral TAVR using a balloon-expandable valve, and 449 who were assigned to surgery in PARTNER 3. At baseline, the mean age of patients was 73 years, 69% were male, and the average STS (Society of Thoracic Surgeons) Risk Score was 1.9%. Rates of other comorbidities were generally low.
Patients in both groups reported a mild baseline impairment in health status. The mean Kansas City Cardiomyopathy Questionnaire–Overall Summary (KCCQ-OS) score was 70, “which corresponds to only New York Heart Association Class II symptoms,” Dr. Baron said. “The SF-36 [Short Form 36] physical summary score was 44 for both groups, which is approximately half of a standard deviation below the population mean.”
As expected, patients who underwent TAVR showed substantially improved health status at 1 month based on the KCCQ-OS (mean difference,16 points; P less than .001). However, in contrast to prior studies, the researchers observed a persistent, although attenuated, benefit of TAVR over SAVR in disease-specific health status at 6 and 12 months (mean difference in KCCQ-OS of 2.6 and 1.8 points respectively; P less than .04 for both).
Dr. Baron said that a sustained benefit of TAVR over SAVR at 6 months and 1 year was observed on several KCCQ subscales, but a similar benefit was not noted on the generic health status measures such as the SF-36 physical summary score. “That’s likely reflective of the fact that, as a disease-specific measure, the KCCQ is much more sensitive in detecting meaningful differences in this population,” she explained. When change in health status was analyzed as an ordinal variable, with death as the worst outcome and large clinical improvement, which was defined as a 20-point or greater increase in the KCCQ-OS score, TAVR showed a significant benefit, compared with surgery at all time points (P less than .05).
In an effort to better understand the mechanism underlying this persistent albeit small late benefit in disease-specific health status with TAVR, the researchers generated cumulative distribution curves to display the proportion of patients who achieved a given change on the KCCQ-OS. A clear separation of the curves emerged, with 5.2% more patients in the TAVR group experiencing a change of at least 20 points, compared with the surgery group. “This suggests that the difference in late health status between the two groups is driven by this 5.2% absolute risk difference in the proportion of patients who experienced a large clinical improvement,” Dr. Baron said at the meeting, which was sponsored by the Cardiovascular Research Foundation.
Next, the researchers performed subgroup analyses to examine the interaction between the 1-year health status benefit of TAVR over surgery and prespecified baseline characteristics including age, gender, STS risk score, ejection fraction, atrial fibrillation, and New York Heart Association (NYHA) class. They observed a significant interaction between NYHA class and treatment effect such that patients who had NYHA class III or IV symptoms at baseline derived greater benefit from TAVR, compared with those who had NYHA class I or II symptoms at baseline.
“This finding suggests that it’s the patients with worse functional impairment at baseline who may be that subset of patients on the cumulative responder curves who gained better health status outcomes with TAVR, compared with surgery in the low-risk population,” Dr. Baron said.
Suzanne V. Arnold, MD, a cardiologist at Saint Luke’s Mid America Heart Institute, Kansas City, Mo., who was an invited discussant, said that it was “remarkable” that patients in the substudy were not particularly symptomatic and yet they still experienced close to a 20-point improvement in the KCCQ-OS score following TAVR, and asked whether frailty may have played a role in the 1.8-point adjusted difference in the KCCQ-OS score between TAVR and surgery at 1 year. Dr. Baron responded that she and her colleagues performed a subgroup analysis of patients who had two or more markers of frailty versus those who had one or less. Noting that there were only 20 patients in that subgroup, she said there was a significant signal that patients who were considered have two or more frail measures were considered to do much better with TAVR.
Dr. Baron concluded that the study’s overall findings, taken together with the clinical outcomes of the PARTNER 3 trial, “further support the use of TAVR in patients with severe [aortic stenosis] at low surgical risk. Longer-term follow up is needed (and ongoing) to determine whether the health status benefits of TAVR at 1 year are durable.”
The content of the study was published online at the time of presentation (J Am Coll Cardiol 2019 Sep 29. doi: 10.1016/j.jacc.2019.09.007). The PARTNER 3 quality of life substudy was funded by Edwards Lifesciences. Dr. Baron disclosed research funding and advisory board compensation from Boston Scientific Corp and consulting fees from Edwards Lifesciences.
REPORTING FROM TCT 2019
Bariatric surgery tied to fewer cerebrovascular events
PHILADELPHIA – Obese people living in the United Kingdom who underwent bariatric surgery had a two-thirds lower rate of major cerebrovascular events than that of a matched group of obese residents who did not undergo bariatric surgery, in a retrospective study of 8,424 people followed for a mean of just over 11 years.
Although the cut in cerebrovascular events that linked with bariatric surgery shown by the analysis was mostly driven by a reduced rate of transient ischemic attacks, a potentially unreliable diagnosis, the results showed consistent reductions in the rates of acute ischemic strokes as well as in acute, nontraumatic intracranial hemorrhages, two other components of the combined primary endpoint, Maddalena Ardissino, MBBS, said at the American Heart Association scientific sessions.
This finding of an apparent benefit from bariatric surgery in obese patients in a large U.K. database confirms other findings from a “fast-growing” evidence base showing benefits from bariatric surgery for reducing other types of cardiovascular disease events, said Dr. Ardissino, a researcher at Imperial College, London. However, the impact of bariatric surgery specifically on cerebrovascular events had not received much attention in published studies, she noted.
Her study used data collected by the Clinical Practice Research Datalink, which has primary and secondary care health records for about 42 million U.K. residents. The researchers focused on more than 251,000 obese U.K. adults (body mass index of 30 kg/m2 or greater) without a history of a cerebrovascular event who had at least 1 year of follow-up, a data file that included 4,212 adults who had undergone bariatric surgery. Their analysis matched these surgical patients with an equal number of obese adults who did not have surgery, pairing the cases and controls based on age, sex, and BMI. The resulting matched cohorts each averaged 50 years old, with a mean BMI of 40.5 kg/m2.
During just over 11 years of average follow-up, the incidence of acute ischemic stroke, acute intracranial hemorrhage, subarachnoid hemorrhage, or transient ischemic attack was about 1.3% in those without bariatric surgery and about 0.4% in those who had surgery, an absolute risk reduction of 0.9 linked with surgery and a relative risk reduction of 65% that was statistically significant, Dr. Ardissino reported. All-cause mortality was about 70% lower in the group that underwent bariatric surgery compared with those who did not have surgery, a finding that confirmed prior reports. She cautioned that the analysis was limited by a relatively low number of total events, and by the small number of criteria used for cohort matching that might have left unadjusted certain potential confounders such as the level of engagement people had with their medical care.
SOURCE: Ardissino M. AHA 2019, Abstract 335.
PHILADELPHIA – Obese people living in the United Kingdom who underwent bariatric surgery had a two-thirds lower rate of major cerebrovascular events than that of a matched group of obese residents who did not undergo bariatric surgery, in a retrospective study of 8,424 people followed for a mean of just over 11 years.
Although the cut in cerebrovascular events that linked with bariatric surgery shown by the analysis was mostly driven by a reduced rate of transient ischemic attacks, a potentially unreliable diagnosis, the results showed consistent reductions in the rates of acute ischemic strokes as well as in acute, nontraumatic intracranial hemorrhages, two other components of the combined primary endpoint, Maddalena Ardissino, MBBS, said at the American Heart Association scientific sessions.
This finding of an apparent benefit from bariatric surgery in obese patients in a large U.K. database confirms other findings from a “fast-growing” evidence base showing benefits from bariatric surgery for reducing other types of cardiovascular disease events, said Dr. Ardissino, a researcher at Imperial College, London. However, the impact of bariatric surgery specifically on cerebrovascular events had not received much attention in published studies, she noted.
Her study used data collected by the Clinical Practice Research Datalink, which has primary and secondary care health records for about 42 million U.K. residents. The researchers focused on more than 251,000 obese U.K. adults (body mass index of 30 kg/m2 or greater) without a history of a cerebrovascular event who had at least 1 year of follow-up, a data file that included 4,212 adults who had undergone bariatric surgery. Their analysis matched these surgical patients with an equal number of obese adults who did not have surgery, pairing the cases and controls based on age, sex, and BMI. The resulting matched cohorts each averaged 50 years old, with a mean BMI of 40.5 kg/m2.
During just over 11 years of average follow-up, the incidence of acute ischemic stroke, acute intracranial hemorrhage, subarachnoid hemorrhage, or transient ischemic attack was about 1.3% in those without bariatric surgery and about 0.4% in those who had surgery, an absolute risk reduction of 0.9 linked with surgery and a relative risk reduction of 65% that was statistically significant, Dr. Ardissino reported. All-cause mortality was about 70% lower in the group that underwent bariatric surgery compared with those who did not have surgery, a finding that confirmed prior reports. She cautioned that the analysis was limited by a relatively low number of total events, and by the small number of criteria used for cohort matching that might have left unadjusted certain potential confounders such as the level of engagement people had with their medical care.
SOURCE: Ardissino M. AHA 2019, Abstract 335.
PHILADELPHIA – Obese people living in the United Kingdom who underwent bariatric surgery had a two-thirds lower rate of major cerebrovascular events than that of a matched group of obese residents who did not undergo bariatric surgery, in a retrospective study of 8,424 people followed for a mean of just over 11 years.
Although the cut in cerebrovascular events that linked with bariatric surgery shown by the analysis was mostly driven by a reduced rate of transient ischemic attacks, a potentially unreliable diagnosis, the results showed consistent reductions in the rates of acute ischemic strokes as well as in acute, nontraumatic intracranial hemorrhages, two other components of the combined primary endpoint, Maddalena Ardissino, MBBS, said at the American Heart Association scientific sessions.
This finding of an apparent benefit from bariatric surgery in obese patients in a large U.K. database confirms other findings from a “fast-growing” evidence base showing benefits from bariatric surgery for reducing other types of cardiovascular disease events, said Dr. Ardissino, a researcher at Imperial College, London. However, the impact of bariatric surgery specifically on cerebrovascular events had not received much attention in published studies, she noted.
Her study used data collected by the Clinical Practice Research Datalink, which has primary and secondary care health records for about 42 million U.K. residents. The researchers focused on more than 251,000 obese U.K. adults (body mass index of 30 kg/m2 or greater) without a history of a cerebrovascular event who had at least 1 year of follow-up, a data file that included 4,212 adults who had undergone bariatric surgery. Their analysis matched these surgical patients with an equal number of obese adults who did not have surgery, pairing the cases and controls based on age, sex, and BMI. The resulting matched cohorts each averaged 50 years old, with a mean BMI of 40.5 kg/m2.
During just over 11 years of average follow-up, the incidence of acute ischemic stroke, acute intracranial hemorrhage, subarachnoid hemorrhage, or transient ischemic attack was about 1.3% in those without bariatric surgery and about 0.4% in those who had surgery, an absolute risk reduction of 0.9 linked with surgery and a relative risk reduction of 65% that was statistically significant, Dr. Ardissino reported. All-cause mortality was about 70% lower in the group that underwent bariatric surgery compared with those who did not have surgery, a finding that confirmed prior reports. She cautioned that the analysis was limited by a relatively low number of total events, and by the small number of criteria used for cohort matching that might have left unadjusted certain potential confounders such as the level of engagement people had with their medical care.
SOURCE: Ardissino M. AHA 2019, Abstract 335.
REPORTING FROM AHA 2019
Lp(a) molar concentration flags CVD, diabetes risk
Lipoprotein(a) molar concentration, rather than apolipoprotein(a) size, appears to be the factor that drives lipoprotein(a)-based cardiovascular disease, according to research published in the Journal of the American College of Cardiology.
The causal association between lipoprotein(a), or Lp(a), and cardiovascular disease has been previously established, but exactly what attribute of Lp(a) is related to cardiovascular risk is not known, Daniel F. Gudbjartsson, PhD, of deCODE genetics and the University of Iceland in Reykjavik, and colleagues wrote in their study. The researchers set out to determine whether Lp(a) molar concentration or apolipoprotein(a), or apo(a), size affects cardiovascular risk. In addition, Dr. Gudbjartsson and colleagues examined the relationship between Lp(a) and type 2 diabetes. While low levels of Lp(a) have been linked to type 2 diabetes, the researchers sought to examine whether low Lp(a) molar concentration levels were also associated with type 2 diabetes risk.
“With Lp(a)-lowering drugs being developed, it is important to understand which attributes of Lp(a) best capture the cardiovascular risk and the consequences of Lp(a) lowering,” noted Dr. Gudbjartsson and colleagues.
Using Mendelian randomization, the researchers assessed Lp(a) molar concentration and kringle IV type 2 (KIV-2) repeat sequence variants to determine a causal relationship between both variants and disease risk. Lp(a) molar concentration serum samples were measured using particle-enhanced turbidimetric immunoassay, while KIV-2 repeats were genotyped with real-time polymerase chain reaction.
Overall, 143,087 participants from Iceland had their genetic information analyzed; of these, 17,715 participants had coronary artery disease, and 8,734 had type 2 diabetes. Lp(a) molecular concentration was analyzed in 12,137 participants and genetically imputed into 130,950 Icelanders, and KIV-2 repeats were estimated in 22,771 Icelanders and genetically imputed into 120,316 Icelanders.
Dr. Gudbjartsson and colleagues found there was a dose-dependent association between Lp(a) molar concentration and risk of coronary artery disease (CAD), peripheral artery disease, aortic valve stenosis, heart failure, and lifespan. In participants in whom Lp(a) molar concentration was at the 79th percentile (50 units of molarity [nM]), the odds ratio was 1.11, and for those in the 99th percentile (250 nM), there was an odds ratio of 2.01 when compared with participants with a median Lp(a) molar concentration of 14 nM. “Lp(a) molar concentration fully explained the Lp(a) association with CAD, and there was no residual association with apo(a) size,” the researchers said.
Participants who were not at increased risk for CAD included those with few KIV-2 repeats and participants with the splice variant G4925A. “This suggested that risk prediction based on Lp(a) should only depend on molar concentration and that treatment of Lp(a) should focus on lowering the molar concentration in subjects with high Lp(a) levels, regardless of the apo(a) size distribution,” Dr. Gudbjartsson and colleagues wrote.
Among participants with type 2 diabetes examined, the 10% of participants with Lp(a) molar concentrations of less than 3.5 nM were at the highest risk of developing type 2 diabetes.
In an accompanying editorial, Benoit J. Arsenault, PhD, of the Quebec Heart and Lung Institute, said that the findings of an association between Lp(a) concentration and atherosclerotic cardiovascular diseases (ASCVD) from Gudbjartsson et al. are important, particularly if they can be replicated in more diverse populations (doi: 10.1016/j.jacc.2019.06.083). “Investigating the association between Lp(a) levels, apo(a) isoform size, and ASCVD risk in different populations is important because the distribution of Lp(a) levels appears to be different across ethnic groups,” he said.
Despite the link between absolute Lp(a) concentrations and cardiovascular disease, cardiovascular outcome trials will need be conducted, Dr. Arsenault noted.
“In the post-statin and post-genomic era, finding much needed therapeutic targets for residual cardiovascular risk can be compared to a gold-digging expedition. Like a map to the location of the gold, GWAS [genome-wide association studies] and Mendelian randomization studies are consistently pointing us in the direction of Lp(a),” he said. “It is time to coordinate our efforts to dig where the map told us, to see once and for all if we will find the golden target of residual cardiovascular risk that we are hoping for and to give hope to high-risk patients with elevated Lp(a) levels.”
Dr. Gudbjartsson and 19 other authors reported being employees of deCODE genetics, owned by Amgen, which is developing Lp(a)-lowering drugs related to the study findings. The other authors reported no relevant conflict of interest. Dr. Arsenault reported being supported by the Fonds de recherche du Québec: Santé and the Canadian Institutes of Health Research; has received research funding from Pfizer, Merck, and Ionis; and was a former consultant for Pfizer and Novartis.
SOURCE: Gudbjartsson DF et al. J Am Coll Cardiol. 2019. doi: 10.1016/j.jacc.2019.10.019.
Lipoprotein(a) molar concentration, rather than apolipoprotein(a) size, appears to be the factor that drives lipoprotein(a)-based cardiovascular disease, according to research published in the Journal of the American College of Cardiology.
The causal association between lipoprotein(a), or Lp(a), and cardiovascular disease has been previously established, but exactly what attribute of Lp(a) is related to cardiovascular risk is not known, Daniel F. Gudbjartsson, PhD, of deCODE genetics and the University of Iceland in Reykjavik, and colleagues wrote in their study. The researchers set out to determine whether Lp(a) molar concentration or apolipoprotein(a), or apo(a), size affects cardiovascular risk. In addition, Dr. Gudbjartsson and colleagues examined the relationship between Lp(a) and type 2 diabetes. While low levels of Lp(a) have been linked to type 2 diabetes, the researchers sought to examine whether low Lp(a) molar concentration levels were also associated with type 2 diabetes risk.
“With Lp(a)-lowering drugs being developed, it is important to understand which attributes of Lp(a) best capture the cardiovascular risk and the consequences of Lp(a) lowering,” noted Dr. Gudbjartsson and colleagues.
Using Mendelian randomization, the researchers assessed Lp(a) molar concentration and kringle IV type 2 (KIV-2) repeat sequence variants to determine a causal relationship between both variants and disease risk. Lp(a) molar concentration serum samples were measured using particle-enhanced turbidimetric immunoassay, while KIV-2 repeats were genotyped with real-time polymerase chain reaction.
Overall, 143,087 participants from Iceland had their genetic information analyzed; of these, 17,715 participants had coronary artery disease, and 8,734 had type 2 diabetes. Lp(a) molecular concentration was analyzed in 12,137 participants and genetically imputed into 130,950 Icelanders, and KIV-2 repeats were estimated in 22,771 Icelanders and genetically imputed into 120,316 Icelanders.
Dr. Gudbjartsson and colleagues found there was a dose-dependent association between Lp(a) molar concentration and risk of coronary artery disease (CAD), peripheral artery disease, aortic valve stenosis, heart failure, and lifespan. In participants in whom Lp(a) molar concentration was at the 79th percentile (50 units of molarity [nM]), the odds ratio was 1.11, and for those in the 99th percentile (250 nM), there was an odds ratio of 2.01 when compared with participants with a median Lp(a) molar concentration of 14 nM. “Lp(a) molar concentration fully explained the Lp(a) association with CAD, and there was no residual association with apo(a) size,” the researchers said.
Participants who were not at increased risk for CAD included those with few KIV-2 repeats and participants with the splice variant G4925A. “This suggested that risk prediction based on Lp(a) should only depend on molar concentration and that treatment of Lp(a) should focus on lowering the molar concentration in subjects with high Lp(a) levels, regardless of the apo(a) size distribution,” Dr. Gudbjartsson and colleagues wrote.
Among participants with type 2 diabetes examined, the 10% of participants with Lp(a) molar concentrations of less than 3.5 nM were at the highest risk of developing type 2 diabetes.
In an accompanying editorial, Benoit J. Arsenault, PhD, of the Quebec Heart and Lung Institute, said that the findings of an association between Lp(a) concentration and atherosclerotic cardiovascular diseases (ASCVD) from Gudbjartsson et al. are important, particularly if they can be replicated in more diverse populations (doi: 10.1016/j.jacc.2019.06.083). “Investigating the association between Lp(a) levels, apo(a) isoform size, and ASCVD risk in different populations is important because the distribution of Lp(a) levels appears to be different across ethnic groups,” he said.
Despite the link between absolute Lp(a) concentrations and cardiovascular disease, cardiovascular outcome trials will need be conducted, Dr. Arsenault noted.
“In the post-statin and post-genomic era, finding much needed therapeutic targets for residual cardiovascular risk can be compared to a gold-digging expedition. Like a map to the location of the gold, GWAS [genome-wide association studies] and Mendelian randomization studies are consistently pointing us in the direction of Lp(a),” he said. “It is time to coordinate our efforts to dig where the map told us, to see once and for all if we will find the golden target of residual cardiovascular risk that we are hoping for and to give hope to high-risk patients with elevated Lp(a) levels.”
Dr. Gudbjartsson and 19 other authors reported being employees of deCODE genetics, owned by Amgen, which is developing Lp(a)-lowering drugs related to the study findings. The other authors reported no relevant conflict of interest. Dr. Arsenault reported being supported by the Fonds de recherche du Québec: Santé and the Canadian Institutes of Health Research; has received research funding from Pfizer, Merck, and Ionis; and was a former consultant for Pfizer and Novartis.
SOURCE: Gudbjartsson DF et al. J Am Coll Cardiol. 2019. doi: 10.1016/j.jacc.2019.10.019.
Lipoprotein(a) molar concentration, rather than apolipoprotein(a) size, appears to be the factor that drives lipoprotein(a)-based cardiovascular disease, according to research published in the Journal of the American College of Cardiology.
The causal association between lipoprotein(a), or Lp(a), and cardiovascular disease has been previously established, but exactly what attribute of Lp(a) is related to cardiovascular risk is not known, Daniel F. Gudbjartsson, PhD, of deCODE genetics and the University of Iceland in Reykjavik, and colleagues wrote in their study. The researchers set out to determine whether Lp(a) molar concentration or apolipoprotein(a), or apo(a), size affects cardiovascular risk. In addition, Dr. Gudbjartsson and colleagues examined the relationship between Lp(a) and type 2 diabetes. While low levels of Lp(a) have been linked to type 2 diabetes, the researchers sought to examine whether low Lp(a) molar concentration levels were also associated with type 2 diabetes risk.
“With Lp(a)-lowering drugs being developed, it is important to understand which attributes of Lp(a) best capture the cardiovascular risk and the consequences of Lp(a) lowering,” noted Dr. Gudbjartsson and colleagues.
Using Mendelian randomization, the researchers assessed Lp(a) molar concentration and kringle IV type 2 (KIV-2) repeat sequence variants to determine a causal relationship between both variants and disease risk. Lp(a) molar concentration serum samples were measured using particle-enhanced turbidimetric immunoassay, while KIV-2 repeats were genotyped with real-time polymerase chain reaction.
Overall, 143,087 participants from Iceland had their genetic information analyzed; of these, 17,715 participants had coronary artery disease, and 8,734 had type 2 diabetes. Lp(a) molecular concentration was analyzed in 12,137 participants and genetically imputed into 130,950 Icelanders, and KIV-2 repeats were estimated in 22,771 Icelanders and genetically imputed into 120,316 Icelanders.
Dr. Gudbjartsson and colleagues found there was a dose-dependent association between Lp(a) molar concentration and risk of coronary artery disease (CAD), peripheral artery disease, aortic valve stenosis, heart failure, and lifespan. In participants in whom Lp(a) molar concentration was at the 79th percentile (50 units of molarity [nM]), the odds ratio was 1.11, and for those in the 99th percentile (250 nM), there was an odds ratio of 2.01 when compared with participants with a median Lp(a) molar concentration of 14 nM. “Lp(a) molar concentration fully explained the Lp(a) association with CAD, and there was no residual association with apo(a) size,” the researchers said.
Participants who were not at increased risk for CAD included those with few KIV-2 repeats and participants with the splice variant G4925A. “This suggested that risk prediction based on Lp(a) should only depend on molar concentration and that treatment of Lp(a) should focus on lowering the molar concentration in subjects with high Lp(a) levels, regardless of the apo(a) size distribution,” Dr. Gudbjartsson and colleagues wrote.
Among participants with type 2 diabetes examined, the 10% of participants with Lp(a) molar concentrations of less than 3.5 nM were at the highest risk of developing type 2 diabetes.
In an accompanying editorial, Benoit J. Arsenault, PhD, of the Quebec Heart and Lung Institute, said that the findings of an association between Lp(a) concentration and atherosclerotic cardiovascular diseases (ASCVD) from Gudbjartsson et al. are important, particularly if they can be replicated in more diverse populations (doi: 10.1016/j.jacc.2019.06.083). “Investigating the association between Lp(a) levels, apo(a) isoform size, and ASCVD risk in different populations is important because the distribution of Lp(a) levels appears to be different across ethnic groups,” he said.
Despite the link between absolute Lp(a) concentrations and cardiovascular disease, cardiovascular outcome trials will need be conducted, Dr. Arsenault noted.
“In the post-statin and post-genomic era, finding much needed therapeutic targets for residual cardiovascular risk can be compared to a gold-digging expedition. Like a map to the location of the gold, GWAS [genome-wide association studies] and Mendelian randomization studies are consistently pointing us in the direction of Lp(a),” he said. “It is time to coordinate our efforts to dig where the map told us, to see once and for all if we will find the golden target of residual cardiovascular risk that we are hoping for and to give hope to high-risk patients with elevated Lp(a) levels.”
Dr. Gudbjartsson and 19 other authors reported being employees of deCODE genetics, owned by Amgen, which is developing Lp(a)-lowering drugs related to the study findings. The other authors reported no relevant conflict of interest. Dr. Arsenault reported being supported by the Fonds de recherche du Québec: Santé and the Canadian Institutes of Health Research; has received research funding from Pfizer, Merck, and Ionis; and was a former consultant for Pfizer and Novartis.
SOURCE: Gudbjartsson DF et al. J Am Coll Cardiol. 2019. doi: 10.1016/j.jacc.2019.10.019.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Key clinical point:
Major finding: There was a dose-dependent association between Lp(a) molar concentration and risk of coronary artery disease (CAD), peripheral artery disease, aortic valve stenosis, heart failure, and lifespan.
Study details: A case-control study of genetic information from 143,087 Icelandic participants.
Disclosures: Dr. Gudbjartsson and 19 other authors reported being employees of deCODE genetics, owned by Amgen, which is developing Lp(a)-lowering drugs related to the study findings. The other authors reported no relevant conflict of interest. Dr. Arsenault reported being supported by the Fonds de recherche du Québec: Santé and the Canadian Institutes of Health Research; has received research funding from Pfizer, Merck, and Ionis; and was a former consultant for Pfizer and Novartis.
Source: Gudbjartsson DF et al. J Am Coll Cardiol. 2019. doi: 10.1016/j.jacc.2019.10.019.
Women have fewer cardiovascular events after non–ST-segment elevation ACS
While women were found to be at lower risk of major cardiovascular events than men after non–ST-segment elevation acute coronary syndromes (NSTEACS), a new study has also shown that they remain undertreated with guideline-directed therapies.
“These findings underscore the fact that efforts to modify risk factors and implement appropriate treatment strategies in women and men may be a powerful means to further improve outcomes among patients with NSTEACS,” wrote Amy A. Sarma, MD, of Massachusetts General Hospital in Boston and coauthors. The study was published in the Journal of the American College of Cardiology.
To determine if outcomes differed between men and women after NSTEACS, the researchers analyzed 68,730 patients from 10 different clinical trials as part of the Thrombolysis In Myocardial Infarction (TIMI) Study Group. All trials enrolled patients with NSTEACS within 30 days of hospitalization. Across the 10 trials, there were a total of 19,827 women (29%).
Female patients had an average age of 67 years, compared with a mean age of 62 years for men. Women were also more likely to have had hypertension, diabetes, or prior heart failure, though less likely to have had a prior MI. In regard to treatment strategies for NSTEACS, women were less likely to receive aspirin, P2Y12 inhibitors, or statins. Women at high risk were also less likely to receive aspirin, P2Y12 inhibitors, or statins.
Before adjusted analysis, women and men had a similar risk of major adverse cardiovascular events (MACE) – defined as cardiovascular death, MI, or stroke – after NSTEACS (hazard ratio, 1.04; 95% confidence interval, 0.99-1.09; P = .16). However, women were found to be at increased risk of cardiovascular death (HR, 1.16; 95% CI, 1.02-1.32; P = .03), all-cause mortality (HR, 1.12; 95% CI, 1.01-1.24; P = .03), and stroke (HR, 1.19; 95% CI, 1.03-1.37; P = .02).
After adjusting for baseline risk predictors, women were found to have a 7% lower risk of MACE (adjusted HR, 0.93; 95% CI, 0.89-0.98; P = .005), along with a 15% lower risk of cardiovascular death (aHR, 0.85; 95% CI, 0.76-0.96; P = .008) and a 16% lower risk of all-cause death (aHR, 0.84; 95% CI, 0.78-0.90; P less than .0001). Additional adjustments for guideline-based therapies did not significantly alter the risk estimates.
In an accompanying editorial, Michael E. Farkouh, MD, and Wendy Tsang, MD, of the University of Toronto noted that this study from Sarma et al. underlines the “lack of progress made in addressing sex inequality in the care for women with ACS” (J Am Coll Cardiol. 2019 Dec 9. doi: 10.1016/j.jacc.2019.10.017).
Though Dr. Farkouh and Dr. Tsang were not surprised that the women in the study were older than the men, as women typically develop cardiovascular disease later, they noted that the women also presented with higher baseline risk. Could this be because of the “persistent perception that coronary disease is a male disease?” They cited the treatment-risk paradox and an emphasis on diagnosing obstructive coronary disease – typically seen in men – as potential contributors to underdiagnosis and undertreatment in at-risk women.
“That this care gap for women with cardiovascular diseases continues to persist, even in well-run contemporary landmark ACS trials, highlights how challenging it is to address,” they wrote.
Dr. Sarma and coauthors acknowledged their study’s potential limitations, including the 10 trials differing in study design, enrollment timing, treatments tested, and follow-up duration. They also noted that the cohort of patients were all at moderate to high risk, which may not make the findings generalizable to the broader NSTEACS patient population.
The study authors reported numerous potential conflicts of interest, including receiving research grants from – and serving as a consultant or on the advisory board of – various pharmaceutical and medical companies. Dr. Farkouh reported receiving research support from Amgen and Novo Nordisk, and Dr. Tsang is supported by a National New Investigator Award from the Heart and Stroke Foundation of Canada.
SOURCE: Sarma AA et al. J Am Coll Cardiol. 2019 Dec 9. doi: 10.1016/j.jacc.2019.09.065.
While women were found to be at lower risk of major cardiovascular events than men after non–ST-segment elevation acute coronary syndromes (NSTEACS), a new study has also shown that they remain undertreated with guideline-directed therapies.
“These findings underscore the fact that efforts to modify risk factors and implement appropriate treatment strategies in women and men may be a powerful means to further improve outcomes among patients with NSTEACS,” wrote Amy A. Sarma, MD, of Massachusetts General Hospital in Boston and coauthors. The study was published in the Journal of the American College of Cardiology.
To determine if outcomes differed between men and women after NSTEACS, the researchers analyzed 68,730 patients from 10 different clinical trials as part of the Thrombolysis In Myocardial Infarction (TIMI) Study Group. All trials enrolled patients with NSTEACS within 30 days of hospitalization. Across the 10 trials, there were a total of 19,827 women (29%).
Female patients had an average age of 67 years, compared with a mean age of 62 years for men. Women were also more likely to have had hypertension, diabetes, or prior heart failure, though less likely to have had a prior MI. In regard to treatment strategies for NSTEACS, women were less likely to receive aspirin, P2Y12 inhibitors, or statins. Women at high risk were also less likely to receive aspirin, P2Y12 inhibitors, or statins.
Before adjusted analysis, women and men had a similar risk of major adverse cardiovascular events (MACE) – defined as cardiovascular death, MI, or stroke – after NSTEACS (hazard ratio, 1.04; 95% confidence interval, 0.99-1.09; P = .16). However, women were found to be at increased risk of cardiovascular death (HR, 1.16; 95% CI, 1.02-1.32; P = .03), all-cause mortality (HR, 1.12; 95% CI, 1.01-1.24; P = .03), and stroke (HR, 1.19; 95% CI, 1.03-1.37; P = .02).
After adjusting for baseline risk predictors, women were found to have a 7% lower risk of MACE (adjusted HR, 0.93; 95% CI, 0.89-0.98; P = .005), along with a 15% lower risk of cardiovascular death (aHR, 0.85; 95% CI, 0.76-0.96; P = .008) and a 16% lower risk of all-cause death (aHR, 0.84; 95% CI, 0.78-0.90; P less than .0001). Additional adjustments for guideline-based therapies did not significantly alter the risk estimates.
In an accompanying editorial, Michael E. Farkouh, MD, and Wendy Tsang, MD, of the University of Toronto noted that this study from Sarma et al. underlines the “lack of progress made in addressing sex inequality in the care for women with ACS” (J Am Coll Cardiol. 2019 Dec 9. doi: 10.1016/j.jacc.2019.10.017).
Though Dr. Farkouh and Dr. Tsang were not surprised that the women in the study were older than the men, as women typically develop cardiovascular disease later, they noted that the women also presented with higher baseline risk. Could this be because of the “persistent perception that coronary disease is a male disease?” They cited the treatment-risk paradox and an emphasis on diagnosing obstructive coronary disease – typically seen in men – as potential contributors to underdiagnosis and undertreatment in at-risk women.
“That this care gap for women with cardiovascular diseases continues to persist, even in well-run contemporary landmark ACS trials, highlights how challenging it is to address,” they wrote.
Dr. Sarma and coauthors acknowledged their study’s potential limitations, including the 10 trials differing in study design, enrollment timing, treatments tested, and follow-up duration. They also noted that the cohort of patients were all at moderate to high risk, which may not make the findings generalizable to the broader NSTEACS patient population.
The study authors reported numerous potential conflicts of interest, including receiving research grants from – and serving as a consultant or on the advisory board of – various pharmaceutical and medical companies. Dr. Farkouh reported receiving research support from Amgen and Novo Nordisk, and Dr. Tsang is supported by a National New Investigator Award from the Heart and Stroke Foundation of Canada.
SOURCE: Sarma AA et al. J Am Coll Cardiol. 2019 Dec 9. doi: 10.1016/j.jacc.2019.09.065.
While women were found to be at lower risk of major cardiovascular events than men after non–ST-segment elevation acute coronary syndromes (NSTEACS), a new study has also shown that they remain undertreated with guideline-directed therapies.
“These findings underscore the fact that efforts to modify risk factors and implement appropriate treatment strategies in women and men may be a powerful means to further improve outcomes among patients with NSTEACS,” wrote Amy A. Sarma, MD, of Massachusetts General Hospital in Boston and coauthors. The study was published in the Journal of the American College of Cardiology.
To determine if outcomes differed between men and women after NSTEACS, the researchers analyzed 68,730 patients from 10 different clinical trials as part of the Thrombolysis In Myocardial Infarction (TIMI) Study Group. All trials enrolled patients with NSTEACS within 30 days of hospitalization. Across the 10 trials, there were a total of 19,827 women (29%).
Female patients had an average age of 67 years, compared with a mean age of 62 years for men. Women were also more likely to have had hypertension, diabetes, or prior heart failure, though less likely to have had a prior MI. In regard to treatment strategies for NSTEACS, women were less likely to receive aspirin, P2Y12 inhibitors, or statins. Women at high risk were also less likely to receive aspirin, P2Y12 inhibitors, or statins.
Before adjusted analysis, women and men had a similar risk of major adverse cardiovascular events (MACE) – defined as cardiovascular death, MI, or stroke – after NSTEACS (hazard ratio, 1.04; 95% confidence interval, 0.99-1.09; P = .16). However, women were found to be at increased risk of cardiovascular death (HR, 1.16; 95% CI, 1.02-1.32; P = .03), all-cause mortality (HR, 1.12; 95% CI, 1.01-1.24; P = .03), and stroke (HR, 1.19; 95% CI, 1.03-1.37; P = .02).
After adjusting for baseline risk predictors, women were found to have a 7% lower risk of MACE (adjusted HR, 0.93; 95% CI, 0.89-0.98; P = .005), along with a 15% lower risk of cardiovascular death (aHR, 0.85; 95% CI, 0.76-0.96; P = .008) and a 16% lower risk of all-cause death (aHR, 0.84; 95% CI, 0.78-0.90; P less than .0001). Additional adjustments for guideline-based therapies did not significantly alter the risk estimates.
In an accompanying editorial, Michael E. Farkouh, MD, and Wendy Tsang, MD, of the University of Toronto noted that this study from Sarma et al. underlines the “lack of progress made in addressing sex inequality in the care for women with ACS” (J Am Coll Cardiol. 2019 Dec 9. doi: 10.1016/j.jacc.2019.10.017).
Though Dr. Farkouh and Dr. Tsang were not surprised that the women in the study were older than the men, as women typically develop cardiovascular disease later, they noted that the women also presented with higher baseline risk. Could this be because of the “persistent perception that coronary disease is a male disease?” They cited the treatment-risk paradox and an emphasis on diagnosing obstructive coronary disease – typically seen in men – as potential contributors to underdiagnosis and undertreatment in at-risk women.
“That this care gap for women with cardiovascular diseases continues to persist, even in well-run contemporary landmark ACS trials, highlights how challenging it is to address,” they wrote.
Dr. Sarma and coauthors acknowledged their study’s potential limitations, including the 10 trials differing in study design, enrollment timing, treatments tested, and follow-up duration. They also noted that the cohort of patients were all at moderate to high risk, which may not make the findings generalizable to the broader NSTEACS patient population.
The study authors reported numerous potential conflicts of interest, including receiving research grants from – and serving as a consultant or on the advisory board of – various pharmaceutical and medical companies. Dr. Farkouh reported receiving research support from Amgen and Novo Nordisk, and Dr. Tsang is supported by a National New Investigator Award from the Heart and Stroke Foundation of Canada.
SOURCE: Sarma AA et al. J Am Coll Cardiol. 2019 Dec 9. doi: 10.1016/j.jacc.2019.09.065.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Key clinical point: Despite being undertreated with guideline-directed therapies, women have a lower risk of recurrent cardiovascular events after non–ST-segment elevation acute coronary syndromes.
Major finding: After adjustment for baseline risk predictors, women were found to have a 7% lower risk of major adverse cardiovascular events (adjusted hazard ratio, 0.93; 95% confidence interval, 0.89-0.98, P = 0.005).
Study details: A sex-specific analysis of cardiovascular outcomes in 68,730 patients with non–ST-segment elevation acute coronary syndromes across 10 clinical trials.
Disclosures: The authors reported numerous potential conflicts of interest, including receiving research grants from – and serving as a consultant or on the advisory board of – various pharmaceutical and medical companies.
Source: Sarma AA et al. J Am Coll Cardiol. 2019 Dec 9. doi: 10.1016/j.jacc.2019.09.065.
Genetic test stratified AFib patients with low CHA2DS2-VASc scores
PHILADELPHIA – A 32-gene screening test for stroke risk identified a subgroup of atrial fibrillation (AFib) patients with an elevated rate of ischemic strokes despite having a low stroke risk by conventional criteria by their CHA2DS2-VASc score in a post-hoc analysis of more than 11,000 patients enrolled in a recent drug trial.
Overall, AFib patients in the highest tertile for genetic risk based on a 32 gene-loci test had a 31% increase rate of ischemic stroke during a median 2.8 years of follow-up compared with patients in the tertile with the lowest risk based on the 32-loci screen, Nicholas A. Marston, MD, said at the American Heart Association scientific sessions. This suggested that the genetic test had roughly the same association with an increased stroke risk as several components of the CHA2DS2-VASc score, such as female sex, an age of 65-74 years old, or having heart failure as a comorbidity, each of which links with an increased risk for ischemic stroke of about 31%-38%, Dr. Marston noted.
The genetic test produced even sharper discrimination among the patients with the lowest stroke risk as measured by their CHA2DS2-VASc score (Circulation. 2012 Aug 14;126[7]: 860-5). Among the slightly more than 3,000 patients in the study with a CHA2DS2-VASc score of three or less, those in the subgroup with the highest risk by the 32-loci screen had a stroke rate during follow-up that was 76% higher than those in the low or intermediate tertile for their genetic score. Among the 796 patients with a CHA2DS2-VASc score of just 1 or 2, those who also fell into the highest level of risk on the 32-loci screen had a stroke rate 3.5-fold higher than those with a similar CHA2DS2-VASc score but in the low and intermediate tertiles by the 32-loci screen.
The additional risk prediction provided by the 32-loci test was statistically significant in the analysis of the 3,071 patients with a CHA2DS2-VASc score of 3 or less after adjustment for age, sex, ancestry, and the individual components of the CHA2DS2-VASc score, which includes factors such as hypertension, diabetes, and heart failure, said Dr. Marston, a cardiologist at Brigham and Women’s Hospital in Boston. The 3.5-fold elevation among patients with a high genetic-risk score in the cohort of 796 patients with a CHA2DS2-VASc score of 1 or 2 just missed statistical significance (P = .06), possibly because the number of patients in the analysis was relatively low. Future research should explore the predictive value of the genetic risk score in patients with a CHA2DS2-VASc score of 0 or 1, the “group where therapeutic decisions could be altered” depending on the genetic risk score, he explained.
Dr. Marston and his associates used data collected in the ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48) trial, which was designed to assess the safety and efficacy of the direct-acting oral anticoagulant edoxaban in patients with AFib (New Engl J Med. 2013 Nov 28; 369[21]: 2091-2104). The 32-loci panel to measure a person’s genetic risk for stroke came from a 2018 report by a multinational team of researchers (Nature Genetics. 2018 Apr;50[4]: 524-37). The new analysis applied this 32-loci genetic test panel to 11.164 unrelated AFib patients with European ancestry from the ENGAGE AF-TIMIT 48 database. They divided this cohort into tertiles based on having a low, intermediate, or high stroke risk as assessed by the 32-loci genetic test. The analysis focused on patients enrolled in the trial who had European ancestry because the 32-loci screening test relied predominantly on data collected from people with this genetic background, Dr. Marston said.
SOURCE: Marston NA et al. AHA 2019, Abstract 336.
PHILADELPHIA – A 32-gene screening test for stroke risk identified a subgroup of atrial fibrillation (AFib) patients with an elevated rate of ischemic strokes despite having a low stroke risk by conventional criteria by their CHA2DS2-VASc score in a post-hoc analysis of more than 11,000 patients enrolled in a recent drug trial.
Overall, AFib patients in the highest tertile for genetic risk based on a 32 gene-loci test had a 31% increase rate of ischemic stroke during a median 2.8 years of follow-up compared with patients in the tertile with the lowest risk based on the 32-loci screen, Nicholas A. Marston, MD, said at the American Heart Association scientific sessions. This suggested that the genetic test had roughly the same association with an increased stroke risk as several components of the CHA2DS2-VASc score, such as female sex, an age of 65-74 years old, or having heart failure as a comorbidity, each of which links with an increased risk for ischemic stroke of about 31%-38%, Dr. Marston noted.
The genetic test produced even sharper discrimination among the patients with the lowest stroke risk as measured by their CHA2DS2-VASc score (Circulation. 2012 Aug 14;126[7]: 860-5). Among the slightly more than 3,000 patients in the study with a CHA2DS2-VASc score of three or less, those in the subgroup with the highest risk by the 32-loci screen had a stroke rate during follow-up that was 76% higher than those in the low or intermediate tertile for their genetic score. Among the 796 patients with a CHA2DS2-VASc score of just 1 or 2, those who also fell into the highest level of risk on the 32-loci screen had a stroke rate 3.5-fold higher than those with a similar CHA2DS2-VASc score but in the low and intermediate tertiles by the 32-loci screen.
The additional risk prediction provided by the 32-loci test was statistically significant in the analysis of the 3,071 patients with a CHA2DS2-VASc score of 3 or less after adjustment for age, sex, ancestry, and the individual components of the CHA2DS2-VASc score, which includes factors such as hypertension, diabetes, and heart failure, said Dr. Marston, a cardiologist at Brigham and Women’s Hospital in Boston. The 3.5-fold elevation among patients with a high genetic-risk score in the cohort of 796 patients with a CHA2DS2-VASc score of 1 or 2 just missed statistical significance (P = .06), possibly because the number of patients in the analysis was relatively low. Future research should explore the predictive value of the genetic risk score in patients with a CHA2DS2-VASc score of 0 or 1, the “group where therapeutic decisions could be altered” depending on the genetic risk score, he explained.
Dr. Marston and his associates used data collected in the ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48) trial, which was designed to assess the safety and efficacy of the direct-acting oral anticoagulant edoxaban in patients with AFib (New Engl J Med. 2013 Nov 28; 369[21]: 2091-2104). The 32-loci panel to measure a person’s genetic risk for stroke came from a 2018 report by a multinational team of researchers (Nature Genetics. 2018 Apr;50[4]: 524-37). The new analysis applied this 32-loci genetic test panel to 11.164 unrelated AFib patients with European ancestry from the ENGAGE AF-TIMIT 48 database. They divided this cohort into tertiles based on having a low, intermediate, or high stroke risk as assessed by the 32-loci genetic test. The analysis focused on patients enrolled in the trial who had European ancestry because the 32-loci screening test relied predominantly on data collected from people with this genetic background, Dr. Marston said.
SOURCE: Marston NA et al. AHA 2019, Abstract 336.
PHILADELPHIA – A 32-gene screening test for stroke risk identified a subgroup of atrial fibrillation (AFib) patients with an elevated rate of ischemic strokes despite having a low stroke risk by conventional criteria by their CHA2DS2-VASc score in a post-hoc analysis of more than 11,000 patients enrolled in a recent drug trial.
Overall, AFib patients in the highest tertile for genetic risk based on a 32 gene-loci test had a 31% increase rate of ischemic stroke during a median 2.8 years of follow-up compared with patients in the tertile with the lowest risk based on the 32-loci screen, Nicholas A. Marston, MD, said at the American Heart Association scientific sessions. This suggested that the genetic test had roughly the same association with an increased stroke risk as several components of the CHA2DS2-VASc score, such as female sex, an age of 65-74 years old, or having heart failure as a comorbidity, each of which links with an increased risk for ischemic stroke of about 31%-38%, Dr. Marston noted.
The genetic test produced even sharper discrimination among the patients with the lowest stroke risk as measured by their CHA2DS2-VASc score (Circulation. 2012 Aug 14;126[7]: 860-5). Among the slightly more than 3,000 patients in the study with a CHA2DS2-VASc score of three or less, those in the subgroup with the highest risk by the 32-loci screen had a stroke rate during follow-up that was 76% higher than those in the low or intermediate tertile for their genetic score. Among the 796 patients with a CHA2DS2-VASc score of just 1 or 2, those who also fell into the highest level of risk on the 32-loci screen had a stroke rate 3.5-fold higher than those with a similar CHA2DS2-VASc score but in the low and intermediate tertiles by the 32-loci screen.
The additional risk prediction provided by the 32-loci test was statistically significant in the analysis of the 3,071 patients with a CHA2DS2-VASc score of 3 or less after adjustment for age, sex, ancestry, and the individual components of the CHA2DS2-VASc score, which includes factors such as hypertension, diabetes, and heart failure, said Dr. Marston, a cardiologist at Brigham and Women’s Hospital in Boston. The 3.5-fold elevation among patients with a high genetic-risk score in the cohort of 796 patients with a CHA2DS2-VASc score of 1 or 2 just missed statistical significance (P = .06), possibly because the number of patients in the analysis was relatively low. Future research should explore the predictive value of the genetic risk score in patients with a CHA2DS2-VASc score of 0 or 1, the “group where therapeutic decisions could be altered” depending on the genetic risk score, he explained.
Dr. Marston and his associates used data collected in the ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48) trial, which was designed to assess the safety and efficacy of the direct-acting oral anticoagulant edoxaban in patients with AFib (New Engl J Med. 2013 Nov 28; 369[21]: 2091-2104). The 32-loci panel to measure a person’s genetic risk for stroke came from a 2018 report by a multinational team of researchers (Nature Genetics. 2018 Apr;50[4]: 524-37). The new analysis applied this 32-loci genetic test panel to 11.164 unrelated AFib patients with European ancestry from the ENGAGE AF-TIMIT 48 database. They divided this cohort into tertiles based on having a low, intermediate, or high stroke risk as assessed by the 32-loci genetic test. The analysis focused on patients enrolled in the trial who had European ancestry because the 32-loci screening test relied predominantly on data collected from people with this genetic background, Dr. Marston said.
SOURCE: Marston NA et al. AHA 2019, Abstract 336.
REPORTING FROM AHA 2019