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High CV risk factor burden in young adults a ‘smoldering’ crisis
New data show a high and rising burden of most cardiovascular (CV) risk factors among young adults aged 20-44 years in the United States.
In this age group, over the past 10 years, there has been an increase in the prevalence of diabetes and obesity, no improvement in the prevalence of hypertension, and a decrease in the prevalence of hyperlipidemia.
Yet medical treatment rates for CV risk factors are “surprisingly” low among young adults, study investigator Rishi Wadhera, MD, with Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, told this news organization.
The findings are “extremely concerning. We’re witnessing a smoldering public health crisis. The onset of these risk factors earlier in life is associated with a higher lifetime risk of heart disease and potentially life-threatening,” Dr. Wadhera added.
The study was presented March 5 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation and was simultaneously published in JAMA.
The burden of CV risk factors among young adults is “unacceptably high and increasing,” write the co-authors of a JAMA editorial.
“The time is now for aggressive preventive measures in young adults. Without immediate action there will continue to be a rise in heart disease and the burden it places on patients, families, and communities,” say Norrina Allen, PhD, and John Wilkins, MD, with Northwestern University, Chicago.
Preventing a tsunami of heart disease
The findings stem from a cross-sectional study of 12,294 U.S. adults aged 20-44 years (mean age, 32; 51% women) who participated in National Health and Nutrition Examination Survey (NHANES) cycles for 2009-2010 to 2017-2020.
Overall, the prevalence of hypertension was 9.3% in 2009-2010 and increased to 11.5% in 2017-2020. The prevalence of diabetes rose from 3.0% to 4.1%, and the prevalence of obesity rose from 32.7% to 40.9%. The prevalence of hyperlipidemia decreased from 40.5% to 36.1%.
Black adults consistently had high rates of hypertension during the study period – 16.2% in 2009-2010 and 20.1% in 2017-2020 – and significant increases in hypertension occurred among Mexican American adults (from 6.5% to 9.5%) and other Hispanic adults (from 4.4% to 10.5%), while Mexican American adults had a significant uptick in diabetes (from 4.3% to 7.5%).
Equally concerning, said Dr. Wadhera, is the fact that only about 55% of young adults with hypertension were receiving antihypertensive medication, and just 1 in 2 young adults with diabetes were receiving treatment. “These low rates were driven, in part, by many young adults not being aware of their diagnosis,” he noted.
The NHANES data also show that the percentage of young adults who were treated for hypertension and who achieved blood pressure control did not change significantly over the study period (65.0% in 2009-2010 and 74.8% in 2017-2020). Blood sugar control among young adults being treated for diabetes remained suboptimal throughout the study period (45.5% in 2009-2010 and 56.6% in 2017-2020).
“The fact that blood pressure control and glycemic control are so poor is really worrisome,” Jeffrey Berger, MD, director of the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart, who wasn’t involved in the study, told this news organization.
“Even in the lipid control, while it did get a little bit better, it’s still only around 30%-40%. So, I think we have ways to go as a society,” Dr. Berger noted.
Double down on screening
Dr. Wadhera said “we need to double down on efforts to screen for and treat cardiovascular risk factors like high blood pressure and diabetes in young adults. We need to intensify clinical and public health interventions focused on primordial and primary prevention in young adults now so that we can avoid a tsunami of cardiovascular disease in the long term.”
“It’s critically important that young adults speak with their health care provider about whether – and when – they should undergo screening for high blood pressure, diabetes, and high cholesterol,” Dr. Wadhera added.
Dr. Berger said one problem is that younger people often have a “superman or superwoman” view and don’t comprehend that they are at risk for some of these conditions. Studies such as this “reinforce the idea that it’s never too young to be checked out.”
As a cardiologist who specializes in cardiovascular prevention, Dr. Berger said he sometimes hears patients say things like, “I don’t ever want to need a cardiologist,” or “I hope I never need a cardiologist.”
“My response is, ‘There are many different types of cardiologists,’ and I think it would really be helpful for many people to see a prevention-focused cardiologist way before they have problems,” he said in an interview.
“As a system, medicine has become very good at treating patients with different diseases. I think we need to get better in terms of preventing some of these problems,” Dr. Berger added.
In their editorial, Dr. Allen and Dr. Wilkins say the “foundation of cardiovascular health begins early in life. These worsening trends in risk factors highlight the importance of focusing on prevention in adolescence and young adulthood in order to promote cardiovascular health across the lifetime.”
The study was funded by a grant from the National Heart, Lung, and Blood Institute. Dr. Wadhera has served as a consultant for Abbott and CVS Health. Dr. Wilkins has received personal fees from 3M. Dr. Berger has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
New data show a high and rising burden of most cardiovascular (CV) risk factors among young adults aged 20-44 years in the United States.
In this age group, over the past 10 years, there has been an increase in the prevalence of diabetes and obesity, no improvement in the prevalence of hypertension, and a decrease in the prevalence of hyperlipidemia.
Yet medical treatment rates for CV risk factors are “surprisingly” low among young adults, study investigator Rishi Wadhera, MD, with Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, told this news organization.
The findings are “extremely concerning. We’re witnessing a smoldering public health crisis. The onset of these risk factors earlier in life is associated with a higher lifetime risk of heart disease and potentially life-threatening,” Dr. Wadhera added.
The study was presented March 5 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation and was simultaneously published in JAMA.
The burden of CV risk factors among young adults is “unacceptably high and increasing,” write the co-authors of a JAMA editorial.
“The time is now for aggressive preventive measures in young adults. Without immediate action there will continue to be a rise in heart disease and the burden it places on patients, families, and communities,” say Norrina Allen, PhD, and John Wilkins, MD, with Northwestern University, Chicago.
Preventing a tsunami of heart disease
The findings stem from a cross-sectional study of 12,294 U.S. adults aged 20-44 years (mean age, 32; 51% women) who participated in National Health and Nutrition Examination Survey (NHANES) cycles for 2009-2010 to 2017-2020.
Overall, the prevalence of hypertension was 9.3% in 2009-2010 and increased to 11.5% in 2017-2020. The prevalence of diabetes rose from 3.0% to 4.1%, and the prevalence of obesity rose from 32.7% to 40.9%. The prevalence of hyperlipidemia decreased from 40.5% to 36.1%.
Black adults consistently had high rates of hypertension during the study period – 16.2% in 2009-2010 and 20.1% in 2017-2020 – and significant increases in hypertension occurred among Mexican American adults (from 6.5% to 9.5%) and other Hispanic adults (from 4.4% to 10.5%), while Mexican American adults had a significant uptick in diabetes (from 4.3% to 7.5%).
Equally concerning, said Dr. Wadhera, is the fact that only about 55% of young adults with hypertension were receiving antihypertensive medication, and just 1 in 2 young adults with diabetes were receiving treatment. “These low rates were driven, in part, by many young adults not being aware of their diagnosis,” he noted.
The NHANES data also show that the percentage of young adults who were treated for hypertension and who achieved blood pressure control did not change significantly over the study period (65.0% in 2009-2010 and 74.8% in 2017-2020). Blood sugar control among young adults being treated for diabetes remained suboptimal throughout the study period (45.5% in 2009-2010 and 56.6% in 2017-2020).
“The fact that blood pressure control and glycemic control are so poor is really worrisome,” Jeffrey Berger, MD, director of the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart, who wasn’t involved in the study, told this news organization.
“Even in the lipid control, while it did get a little bit better, it’s still only around 30%-40%. So, I think we have ways to go as a society,” Dr. Berger noted.
Double down on screening
Dr. Wadhera said “we need to double down on efforts to screen for and treat cardiovascular risk factors like high blood pressure and diabetes in young adults. We need to intensify clinical and public health interventions focused on primordial and primary prevention in young adults now so that we can avoid a tsunami of cardiovascular disease in the long term.”
“It’s critically important that young adults speak with their health care provider about whether – and when – they should undergo screening for high blood pressure, diabetes, and high cholesterol,” Dr. Wadhera added.
Dr. Berger said one problem is that younger people often have a “superman or superwoman” view and don’t comprehend that they are at risk for some of these conditions. Studies such as this “reinforce the idea that it’s never too young to be checked out.”
As a cardiologist who specializes in cardiovascular prevention, Dr. Berger said he sometimes hears patients say things like, “I don’t ever want to need a cardiologist,” or “I hope I never need a cardiologist.”
“My response is, ‘There are many different types of cardiologists,’ and I think it would really be helpful for many people to see a prevention-focused cardiologist way before they have problems,” he said in an interview.
“As a system, medicine has become very good at treating patients with different diseases. I think we need to get better in terms of preventing some of these problems,” Dr. Berger added.
In their editorial, Dr. Allen and Dr. Wilkins say the “foundation of cardiovascular health begins early in life. These worsening trends in risk factors highlight the importance of focusing on prevention in adolescence and young adulthood in order to promote cardiovascular health across the lifetime.”
The study was funded by a grant from the National Heart, Lung, and Blood Institute. Dr. Wadhera has served as a consultant for Abbott and CVS Health. Dr. Wilkins has received personal fees from 3M. Dr. Berger has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
New data show a high and rising burden of most cardiovascular (CV) risk factors among young adults aged 20-44 years in the United States.
In this age group, over the past 10 years, there has been an increase in the prevalence of diabetes and obesity, no improvement in the prevalence of hypertension, and a decrease in the prevalence of hyperlipidemia.
Yet medical treatment rates for CV risk factors are “surprisingly” low among young adults, study investigator Rishi Wadhera, MD, with Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, told this news organization.
The findings are “extremely concerning. We’re witnessing a smoldering public health crisis. The onset of these risk factors earlier in life is associated with a higher lifetime risk of heart disease and potentially life-threatening,” Dr. Wadhera added.
The study was presented March 5 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation and was simultaneously published in JAMA.
The burden of CV risk factors among young adults is “unacceptably high and increasing,” write the co-authors of a JAMA editorial.
“The time is now for aggressive preventive measures in young adults. Without immediate action there will continue to be a rise in heart disease and the burden it places on patients, families, and communities,” say Norrina Allen, PhD, and John Wilkins, MD, with Northwestern University, Chicago.
Preventing a tsunami of heart disease
The findings stem from a cross-sectional study of 12,294 U.S. adults aged 20-44 years (mean age, 32; 51% women) who participated in National Health and Nutrition Examination Survey (NHANES) cycles for 2009-2010 to 2017-2020.
Overall, the prevalence of hypertension was 9.3% in 2009-2010 and increased to 11.5% in 2017-2020. The prevalence of diabetes rose from 3.0% to 4.1%, and the prevalence of obesity rose from 32.7% to 40.9%. The prevalence of hyperlipidemia decreased from 40.5% to 36.1%.
Black adults consistently had high rates of hypertension during the study period – 16.2% in 2009-2010 and 20.1% in 2017-2020 – and significant increases in hypertension occurred among Mexican American adults (from 6.5% to 9.5%) and other Hispanic adults (from 4.4% to 10.5%), while Mexican American adults had a significant uptick in diabetes (from 4.3% to 7.5%).
Equally concerning, said Dr. Wadhera, is the fact that only about 55% of young adults with hypertension were receiving antihypertensive medication, and just 1 in 2 young adults with diabetes were receiving treatment. “These low rates were driven, in part, by many young adults not being aware of their diagnosis,” he noted.
The NHANES data also show that the percentage of young adults who were treated for hypertension and who achieved blood pressure control did not change significantly over the study period (65.0% in 2009-2010 and 74.8% in 2017-2020). Blood sugar control among young adults being treated for diabetes remained suboptimal throughout the study period (45.5% in 2009-2010 and 56.6% in 2017-2020).
“The fact that blood pressure control and glycemic control are so poor is really worrisome,” Jeffrey Berger, MD, director of the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart, who wasn’t involved in the study, told this news organization.
“Even in the lipid control, while it did get a little bit better, it’s still only around 30%-40%. So, I think we have ways to go as a society,” Dr. Berger noted.
Double down on screening
Dr. Wadhera said “we need to double down on efforts to screen for and treat cardiovascular risk factors like high blood pressure and diabetes in young adults. We need to intensify clinical and public health interventions focused on primordial and primary prevention in young adults now so that we can avoid a tsunami of cardiovascular disease in the long term.”
“It’s critically important that young adults speak with their health care provider about whether – and when – they should undergo screening for high blood pressure, diabetes, and high cholesterol,” Dr. Wadhera added.
Dr. Berger said one problem is that younger people often have a “superman or superwoman” view and don’t comprehend that they are at risk for some of these conditions. Studies such as this “reinforce the idea that it’s never too young to be checked out.”
As a cardiologist who specializes in cardiovascular prevention, Dr. Berger said he sometimes hears patients say things like, “I don’t ever want to need a cardiologist,” or “I hope I never need a cardiologist.”
“My response is, ‘There are many different types of cardiologists,’ and I think it would really be helpful for many people to see a prevention-focused cardiologist way before they have problems,” he said in an interview.
“As a system, medicine has become very good at treating patients with different diseases. I think we need to get better in terms of preventing some of these problems,” Dr. Berger added.
In their editorial, Dr. Allen and Dr. Wilkins say the “foundation of cardiovascular health begins early in life. These worsening trends in risk factors highlight the importance of focusing on prevention in adolescence and young adulthood in order to promote cardiovascular health across the lifetime.”
The study was funded by a grant from the National Heart, Lung, and Blood Institute. Dr. Wadhera has served as a consultant for Abbott and CVS Health. Dr. Wilkins has received personal fees from 3M. Dr. Berger has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ACC 2023
COORDINATEd effort boosts optimal therapy in patients with T2D and ASCVD
NEW ORLEANS – Twenty cardiology clinics successfully intensified the medical care they gave patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD) after receiving a simple and scalable investigational intervention that gave the clinics’ staffs guidance on best prescribing practices and implementation and also provided quality-improvement feedback.
Within a year, these clinics quadrupled optimal medical management of these patients, compared with control clinics, in a randomized trial involving a total of 43 clinics and 1,049 patients.
“This multifaceted intervention is effective in increasing the prescription of evidence-based therapies in adults with T2D and ASCVD,” Neha J. Pagidipati, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
“The next step is to scale this intervention across cardiology practices” interested in improving the quality of care they deliver to these patients, added Dr. Pagidipati, a cardiologist specializing in cardiometabolic disease prevention at Duke University in Durham, N.C.
The goal is getting patients on triple therapy
The primary outcome of the COORDINATE-Diabetes trial was the change in the number of patients with T2D and ASCVD who received prescriptions for agents from three recommended medication classes and at recommended dosages: a high-intensity statin, a renin-angiotensin system inhibitor (RASi), and at least one agent from either of two classes that have both cardiovascular-protective and antihyperglycemic effects: the sodium-glucose cotransporter 2 (SGLT2) inhibitors, or the glucagonlike peptide 1 (GLP-1)–receptor agonists.
Among the 457 patients treated at the 20 cardiology clinics who received the quality-improvement intervention, 37.9% were on the promoted triple therapy after 12 months, compared with 14.5% of the 588 patients treated at the 23 clinics that continued with their usual care approach. This 23.4–percentage point increase in triple-class prescribing at recommended dosages represented a significant 4.4-fold increase in the goal prescribing endpoint after adjustment for possible confounders, Dr. Pagidipati reported.
Simultaneously with her report, the findings also appeared online in JAMA.
At baseline, 41%-50% of the patients were on both a high-intensity statin and a RASi, with a total of about 58%-67% on a high-intensity statin and about 70%-75% on a RASi. Fewer than 1% of patients were on SGLT2 inhibitors or GLP-1–receptor agonists at baseline. By design, no patient could be on all three categories of medication at baseline.
At their last follow-up visit (after 12 months for 97% of patients, or after 6 months for the remainder) 71% of the patients at practices that received the intervention were on a high-intensity statin, 81% were taking a RASi, and 60% were on an SGLT2 inhibitor or GLP-1–receptor agonist. Among the control patients, 58% were on a high-intensity statin, 68% on a RASi, and 36% were on one of the antihyperglycemic agents.
Effective interventions and the need for a champion
The clinics randomized to the active arm received instruction from a three-member team, either from an in-person or virtual one-time visit, on an intervention comprising several initiatives:
- Analysis of the barriers to evidence-based care at each clinic.
- Development of local interdisciplinary care pathways to address the identified barriers.
- Facilitation of care coordination among clinicians – particularly among cardiology, endocrinology, and primary care clinicians.
- Education of the clinic staff, including provision of educational materials.
- Auditing of clinic performance using specified metrics and feedback on the findings.
Clinics in the usual care group were given current clinical practice guidelines.
The investigational intervention was, by design, “low-tech and designed to be scalable,” explained Dr. Pagidipati, and once the COVID pandemic started the intervention team shifted to a virtual consultation with participating practices that was mostly front-loaded, followed by monthly phone calls to give clinics feedback on their progress.
Among the most helpful aspects of the intervention was involving the entire clinic staff, including pharmacists, nurses, and advanced care practitioners; boosting familiarity with the relevant medications and their appropriate use; and advice on navigating insurance-coverage barriers such as prior authorizations.
“What was most critical was having a local champion who took on making this effort an important part” of what the clinic was trying to do, she explained. “All it takes is passion, and the tenacity of a bulldog,” Dr. Pagidipati said.
Research advances often don’t translate into management changes
“We don’t do a great job of translating findings from trials to patient care, so any method we can use to improve that will improve practice,” commented Kristen B. Campbell, PharmD, a clinical pharmacist at Duke who was not involved in the study.
“Although the trial was not powered to look at patient outcomes, we think that patients will benefit” because all the recommended medication uses have been proven to help patients in prior trials, Dr. Campbell noted.
“A particular strength of this study was its simple design. All the interventions are low-tech and scalable.”
The low level of use of guideline-directed medical therapy in American adults with type 2 diabetes and atherosclerotic cardiovascular disease is “incredible,” said Christopher B. Granger, MD, a senior investigator on the study and a cardiologist and professor at Duke.
The researchers who ran the study are now focused on evaluating which cardiology clinics and patients had the most success from the intervention and are using that information to further refine implementation. They are also planning to encourage cardiology practices as well as other relevant medical groups to incorporate the intervention and implementation model used in the trial. The intervention program is detailed and available at no charge on the COORDINATE-Diabetes website.
COORDINATE-Diabetes received funding from Boehringer Ingelheim and Eli Lilly. Dr. Pagidipati has received personal fees from Boehringer Ingelheim, Lilly, AstraZeneca, Novartis, Novo Nordisk, Merck, and CRISPR Therapeutics, and she has received research grants from Amgen, Novartis, Novo Nordisk, and Eggland’s Best. Dr. Campbell had no disclosures. Dr. Granger has received personal fees and research funding from numerous companies.
NEW ORLEANS – Twenty cardiology clinics successfully intensified the medical care they gave patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD) after receiving a simple and scalable investigational intervention that gave the clinics’ staffs guidance on best prescribing practices and implementation and also provided quality-improvement feedback.
Within a year, these clinics quadrupled optimal medical management of these patients, compared with control clinics, in a randomized trial involving a total of 43 clinics and 1,049 patients.
“This multifaceted intervention is effective in increasing the prescription of evidence-based therapies in adults with T2D and ASCVD,” Neha J. Pagidipati, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
“The next step is to scale this intervention across cardiology practices” interested in improving the quality of care they deliver to these patients, added Dr. Pagidipati, a cardiologist specializing in cardiometabolic disease prevention at Duke University in Durham, N.C.
The goal is getting patients on triple therapy
The primary outcome of the COORDINATE-Diabetes trial was the change in the number of patients with T2D and ASCVD who received prescriptions for agents from three recommended medication classes and at recommended dosages: a high-intensity statin, a renin-angiotensin system inhibitor (RASi), and at least one agent from either of two classes that have both cardiovascular-protective and antihyperglycemic effects: the sodium-glucose cotransporter 2 (SGLT2) inhibitors, or the glucagonlike peptide 1 (GLP-1)–receptor agonists.
Among the 457 patients treated at the 20 cardiology clinics who received the quality-improvement intervention, 37.9% were on the promoted triple therapy after 12 months, compared with 14.5% of the 588 patients treated at the 23 clinics that continued with their usual care approach. This 23.4–percentage point increase in triple-class prescribing at recommended dosages represented a significant 4.4-fold increase in the goal prescribing endpoint after adjustment for possible confounders, Dr. Pagidipati reported.
Simultaneously with her report, the findings also appeared online in JAMA.
At baseline, 41%-50% of the patients were on both a high-intensity statin and a RASi, with a total of about 58%-67% on a high-intensity statin and about 70%-75% on a RASi. Fewer than 1% of patients were on SGLT2 inhibitors or GLP-1–receptor agonists at baseline. By design, no patient could be on all three categories of medication at baseline.
At their last follow-up visit (after 12 months for 97% of patients, or after 6 months for the remainder) 71% of the patients at practices that received the intervention were on a high-intensity statin, 81% were taking a RASi, and 60% were on an SGLT2 inhibitor or GLP-1–receptor agonist. Among the control patients, 58% were on a high-intensity statin, 68% on a RASi, and 36% were on one of the antihyperglycemic agents.
Effective interventions and the need for a champion
The clinics randomized to the active arm received instruction from a three-member team, either from an in-person or virtual one-time visit, on an intervention comprising several initiatives:
- Analysis of the barriers to evidence-based care at each clinic.
- Development of local interdisciplinary care pathways to address the identified barriers.
- Facilitation of care coordination among clinicians – particularly among cardiology, endocrinology, and primary care clinicians.
- Education of the clinic staff, including provision of educational materials.
- Auditing of clinic performance using specified metrics and feedback on the findings.
Clinics in the usual care group were given current clinical practice guidelines.
The investigational intervention was, by design, “low-tech and designed to be scalable,” explained Dr. Pagidipati, and once the COVID pandemic started the intervention team shifted to a virtual consultation with participating practices that was mostly front-loaded, followed by monthly phone calls to give clinics feedback on their progress.
Among the most helpful aspects of the intervention was involving the entire clinic staff, including pharmacists, nurses, and advanced care practitioners; boosting familiarity with the relevant medications and their appropriate use; and advice on navigating insurance-coverage barriers such as prior authorizations.
“What was most critical was having a local champion who took on making this effort an important part” of what the clinic was trying to do, she explained. “All it takes is passion, and the tenacity of a bulldog,” Dr. Pagidipati said.
Research advances often don’t translate into management changes
“We don’t do a great job of translating findings from trials to patient care, so any method we can use to improve that will improve practice,” commented Kristen B. Campbell, PharmD, a clinical pharmacist at Duke who was not involved in the study.
“Although the trial was not powered to look at patient outcomes, we think that patients will benefit” because all the recommended medication uses have been proven to help patients in prior trials, Dr. Campbell noted.
“A particular strength of this study was its simple design. All the interventions are low-tech and scalable.”
The low level of use of guideline-directed medical therapy in American adults with type 2 diabetes and atherosclerotic cardiovascular disease is “incredible,” said Christopher B. Granger, MD, a senior investigator on the study and a cardiologist and professor at Duke.
The researchers who ran the study are now focused on evaluating which cardiology clinics and patients had the most success from the intervention and are using that information to further refine implementation. They are also planning to encourage cardiology practices as well as other relevant medical groups to incorporate the intervention and implementation model used in the trial. The intervention program is detailed and available at no charge on the COORDINATE-Diabetes website.
COORDINATE-Diabetes received funding from Boehringer Ingelheim and Eli Lilly. Dr. Pagidipati has received personal fees from Boehringer Ingelheim, Lilly, AstraZeneca, Novartis, Novo Nordisk, Merck, and CRISPR Therapeutics, and she has received research grants from Amgen, Novartis, Novo Nordisk, and Eggland’s Best. Dr. Campbell had no disclosures. Dr. Granger has received personal fees and research funding from numerous companies.
NEW ORLEANS – Twenty cardiology clinics successfully intensified the medical care they gave patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD) after receiving a simple and scalable investigational intervention that gave the clinics’ staffs guidance on best prescribing practices and implementation and also provided quality-improvement feedback.
Within a year, these clinics quadrupled optimal medical management of these patients, compared with control clinics, in a randomized trial involving a total of 43 clinics and 1,049 patients.
“This multifaceted intervention is effective in increasing the prescription of evidence-based therapies in adults with T2D and ASCVD,” Neha J. Pagidipati, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
“The next step is to scale this intervention across cardiology practices” interested in improving the quality of care they deliver to these patients, added Dr. Pagidipati, a cardiologist specializing in cardiometabolic disease prevention at Duke University in Durham, N.C.
The goal is getting patients on triple therapy
The primary outcome of the COORDINATE-Diabetes trial was the change in the number of patients with T2D and ASCVD who received prescriptions for agents from three recommended medication classes and at recommended dosages: a high-intensity statin, a renin-angiotensin system inhibitor (RASi), and at least one agent from either of two classes that have both cardiovascular-protective and antihyperglycemic effects: the sodium-glucose cotransporter 2 (SGLT2) inhibitors, or the glucagonlike peptide 1 (GLP-1)–receptor agonists.
Among the 457 patients treated at the 20 cardiology clinics who received the quality-improvement intervention, 37.9% were on the promoted triple therapy after 12 months, compared with 14.5% of the 588 patients treated at the 23 clinics that continued with their usual care approach. This 23.4–percentage point increase in triple-class prescribing at recommended dosages represented a significant 4.4-fold increase in the goal prescribing endpoint after adjustment for possible confounders, Dr. Pagidipati reported.
Simultaneously with her report, the findings also appeared online in JAMA.
At baseline, 41%-50% of the patients were on both a high-intensity statin and a RASi, with a total of about 58%-67% on a high-intensity statin and about 70%-75% on a RASi. Fewer than 1% of patients were on SGLT2 inhibitors or GLP-1–receptor agonists at baseline. By design, no patient could be on all three categories of medication at baseline.
At their last follow-up visit (after 12 months for 97% of patients, or after 6 months for the remainder) 71% of the patients at practices that received the intervention were on a high-intensity statin, 81% were taking a RASi, and 60% were on an SGLT2 inhibitor or GLP-1–receptor agonist. Among the control patients, 58% were on a high-intensity statin, 68% on a RASi, and 36% were on one of the antihyperglycemic agents.
Effective interventions and the need for a champion
The clinics randomized to the active arm received instruction from a three-member team, either from an in-person or virtual one-time visit, on an intervention comprising several initiatives:
- Analysis of the barriers to evidence-based care at each clinic.
- Development of local interdisciplinary care pathways to address the identified barriers.
- Facilitation of care coordination among clinicians – particularly among cardiology, endocrinology, and primary care clinicians.
- Education of the clinic staff, including provision of educational materials.
- Auditing of clinic performance using specified metrics and feedback on the findings.
Clinics in the usual care group were given current clinical practice guidelines.
The investigational intervention was, by design, “low-tech and designed to be scalable,” explained Dr. Pagidipati, and once the COVID pandemic started the intervention team shifted to a virtual consultation with participating practices that was mostly front-loaded, followed by monthly phone calls to give clinics feedback on their progress.
Among the most helpful aspects of the intervention was involving the entire clinic staff, including pharmacists, nurses, and advanced care practitioners; boosting familiarity with the relevant medications and their appropriate use; and advice on navigating insurance-coverage barriers such as prior authorizations.
“What was most critical was having a local champion who took on making this effort an important part” of what the clinic was trying to do, she explained. “All it takes is passion, and the tenacity of a bulldog,” Dr. Pagidipati said.
Research advances often don’t translate into management changes
“We don’t do a great job of translating findings from trials to patient care, so any method we can use to improve that will improve practice,” commented Kristen B. Campbell, PharmD, a clinical pharmacist at Duke who was not involved in the study.
“Although the trial was not powered to look at patient outcomes, we think that patients will benefit” because all the recommended medication uses have been proven to help patients in prior trials, Dr. Campbell noted.
“A particular strength of this study was its simple design. All the interventions are low-tech and scalable.”
The low level of use of guideline-directed medical therapy in American adults with type 2 diabetes and atherosclerotic cardiovascular disease is “incredible,” said Christopher B. Granger, MD, a senior investigator on the study and a cardiologist and professor at Duke.
The researchers who ran the study are now focused on evaluating which cardiology clinics and patients had the most success from the intervention and are using that information to further refine implementation. They are also planning to encourage cardiology practices as well as other relevant medical groups to incorporate the intervention and implementation model used in the trial. The intervention program is detailed and available at no charge on the COORDINATE-Diabetes website.
COORDINATE-Diabetes received funding from Boehringer Ingelheim and Eli Lilly. Dr. Pagidipati has received personal fees from Boehringer Ingelheim, Lilly, AstraZeneca, Novartis, Novo Nordisk, Merck, and CRISPR Therapeutics, and she has received research grants from Amgen, Novartis, Novo Nordisk, and Eggland’s Best. Dr. Campbell had no disclosures. Dr. Granger has received personal fees and research funding from numerous companies.
AT ACC 2023
Mini-invasive MV repair as safe, effective as sternotomy surgery but has advantages: UK Mini-Mitral Trial
Patients with degenerative mitral valve (MV) regurgitation that calls for surgery may, for the most part, safely choose either a standard procedure requiring a midline sternotomy or one performed through a minithoracotomy, suggests a randomized comparison of the two techniques.
Still, the minimally invasive approach showed some advantages in the study. Patients’ quality of recovery was about the same with both procedures at 12 weeks, but those who had the minimally invasive thoracoscopy-guided surgery had shown greater improvement 6 weeks earlier.
Also in the UK Mini Mitral Trial, hospital length of stay (LOS) was significantly shorter for patients who underwent the mini-thoracotomy procedure, and that group spent fewer days in the hospital over the following months.
But neither procedure had an edge in terms of postoperative clinical risk in the study. Rates of clinical events, such as death or hospitalization for heart failure (HHF), were about the same over 1 year.
Patients in this trial had been deemed suitable for either of the two surgeries, which were always performed by surgeons specially chosen by the steering committee for their experience and expertise.
This first randomized head-to-head comparison of the two approaches in such patients should make both patients and clinicians more confident about choosing the minimally invasive surgery for degenerative MV disease, said Enoch Akowuah, MD, Newcastle (England) University, United Kingdom.
Dr. Akowuah presented the UK Mini-Mitral Trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
A “main takeaway” for clinical practice from the trial would be that minithoracotomy MV repair “is as safe and effective as conventional sternotomy for degenerative mitral regurgitation,” said discussant Amy E. Simone, PA-C, following Dr. Akowuah’s presentation.
“I think this study is unique in that its focus is on delivering high-quality, cost-efficient care for mitral regurgitation, but also with an emphasis on patients’ goals and wishes,” said Ms. Simone, who directs the Marcus Heart Valve Center of the Piedmont Heart Institute, Atlanta.
Cardiac surgeon Thomas MacGillivray, MD, another discussant, agreed that the data presented from at least this study suggest neither the minithoracotomy nor sternotomy approach is better than the other. But he questioned whether that would hold true if applied to broader clinical practice.
Dr. MacGillivray, of MedStar Washington Hospital Center, Washington, observed that only 330 patients were randomly assigned among a total of 1,167 candidates for candidates for MV repair surgery.
Indeed, he noted, more than 200 declined and about 600 were declared ineligible for the study, “even though it had seemed as if all were appropriate for mitral valve repair. That could be viewed as a significant limitation in terms of scalability in the real world.”
Some of those patients weren’t randomly assigned because they ultimately were not considered appropriate for both procedures, and some expressed a preference for one or the other approach, Dr. Akowuah replied. Those were the most common reasons. Many others did not enter the study, he said, because their mitral regurgitation was functional, not degenerative.
The two randomization groups fared similarly for the primary endpoint reflecting recovery from surgery, so the trial was actually “negative,” Dr. Akowuah said in an interview. However, “I see it as very much a win for minithoracotomy. The outstanding questions for clinicians and patients have been about the clinical efficacy and safety of the technique. And we’ve shown in this trial that minithoracotomy is safe and effective.”
If the minithoracotomy procedure is available, he continued, “and it’s just as clinically effective and safe – and we weren’t sure that was the case until we did this trial – and the repair is almost as durable, then why have a sternotomy?”
The researchers assigned 330 patients with degenerative MV disease who were deemed suitable for either type of surgery to undergo the standard operation via sternotomy or the minithoracotomy procedure at 10 centers in the United Kingdom. The steering committee had hand-selected its 28 experienced surgeons, each of whom performed only one of the two surgeries consistently for the trial’s patients.
The technically more demanding minithoracotomy procedure took longer to perform by a mean of 44 minutes, it prolonged cross-clamp time by 11 minutes, and it required 30 minutes more cardiopulmonary bypass support, Dr. Akowuah reported.
The two patient groups showed no significant differences in the primary endpoint of physical function and ability to return to usual activity levels at 12 weeks, as assessed by scores on the 36-Item Short Form Survey and wrist-worn accelerometer monitoring. At 6 weeks, however, the mini-thoracotomy patients had shown a significant early but temporary advantage for those recovery measures.
The minithoracotomy group clearly fared better, however, on some secondary endpoints. For example, their median hospital LOS was 5 days, compared with 6 days for the sternotomy group (P = .003), and 33.1% of the mini-thoracotomy patients were discharged within 4 days of the surgery, compared with only 15.3% of patients who had the standard procedure (P < .001).
The minithoracotomy group also had marginally more days alive out of the hospital at both 30 days (23.6 days vs. 22.4 days in the sternotomy group) and 90 days (82.7 days and 80.5 days, respectively) after the surgery (P = .03 for both differences).
Safety outcomes at 12 weeks were similar, with no significant differences in rate of death, strokes, MI, or renal impairment, or in ICU length of stay or need for more than 48 hours of mechanical ventilation, Dr. Akowuah reported.
Safety outcomes at 1 year were also similar. Mortality by then was 2.4% for the minithoracotomy patients and 2.5% for the sternotomy group, nor were there significant differences in HHF rates or need for repeat MV surgical repair.
Dr. Akowuah said the patients will be followed for up to 5 years for the primary outcomes, echocardiographic changes, and clinical events.
The minithoracotomy surgery’s longer operative times and specialized equipment make it more a expensive procedure than the standard surgery, he said. “So we need to work out in a cost-effectiveness analysis whether that is offset by the benefits,” such as shorter hospital stays or perhaps fewer transfusions or readmissions.
The study was funded by the United Kingdom’s National Institute for Health and Care Research. Dr. Akowuah reported no relevant financial relationships with industry.
A version of this article first appeared on Medscape.com.
Patients with degenerative mitral valve (MV) regurgitation that calls for surgery may, for the most part, safely choose either a standard procedure requiring a midline sternotomy or one performed through a minithoracotomy, suggests a randomized comparison of the two techniques.
Still, the minimally invasive approach showed some advantages in the study. Patients’ quality of recovery was about the same with both procedures at 12 weeks, but those who had the minimally invasive thoracoscopy-guided surgery had shown greater improvement 6 weeks earlier.
Also in the UK Mini Mitral Trial, hospital length of stay (LOS) was significantly shorter for patients who underwent the mini-thoracotomy procedure, and that group spent fewer days in the hospital over the following months.
But neither procedure had an edge in terms of postoperative clinical risk in the study. Rates of clinical events, such as death or hospitalization for heart failure (HHF), were about the same over 1 year.
Patients in this trial had been deemed suitable for either of the two surgeries, which were always performed by surgeons specially chosen by the steering committee for their experience and expertise.
This first randomized head-to-head comparison of the two approaches in such patients should make both patients and clinicians more confident about choosing the minimally invasive surgery for degenerative MV disease, said Enoch Akowuah, MD, Newcastle (England) University, United Kingdom.
Dr. Akowuah presented the UK Mini-Mitral Trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
A “main takeaway” for clinical practice from the trial would be that minithoracotomy MV repair “is as safe and effective as conventional sternotomy for degenerative mitral regurgitation,” said discussant Amy E. Simone, PA-C, following Dr. Akowuah’s presentation.
“I think this study is unique in that its focus is on delivering high-quality, cost-efficient care for mitral regurgitation, but also with an emphasis on patients’ goals and wishes,” said Ms. Simone, who directs the Marcus Heart Valve Center of the Piedmont Heart Institute, Atlanta.
Cardiac surgeon Thomas MacGillivray, MD, another discussant, agreed that the data presented from at least this study suggest neither the minithoracotomy nor sternotomy approach is better than the other. But he questioned whether that would hold true if applied to broader clinical practice.
Dr. MacGillivray, of MedStar Washington Hospital Center, Washington, observed that only 330 patients were randomly assigned among a total of 1,167 candidates for candidates for MV repair surgery.
Indeed, he noted, more than 200 declined and about 600 were declared ineligible for the study, “even though it had seemed as if all were appropriate for mitral valve repair. That could be viewed as a significant limitation in terms of scalability in the real world.”
Some of those patients weren’t randomly assigned because they ultimately were not considered appropriate for both procedures, and some expressed a preference for one or the other approach, Dr. Akowuah replied. Those were the most common reasons. Many others did not enter the study, he said, because their mitral regurgitation was functional, not degenerative.
The two randomization groups fared similarly for the primary endpoint reflecting recovery from surgery, so the trial was actually “negative,” Dr. Akowuah said in an interview. However, “I see it as very much a win for minithoracotomy. The outstanding questions for clinicians and patients have been about the clinical efficacy and safety of the technique. And we’ve shown in this trial that minithoracotomy is safe and effective.”
If the minithoracotomy procedure is available, he continued, “and it’s just as clinically effective and safe – and we weren’t sure that was the case until we did this trial – and the repair is almost as durable, then why have a sternotomy?”
The researchers assigned 330 patients with degenerative MV disease who were deemed suitable for either type of surgery to undergo the standard operation via sternotomy or the minithoracotomy procedure at 10 centers in the United Kingdom. The steering committee had hand-selected its 28 experienced surgeons, each of whom performed only one of the two surgeries consistently for the trial’s patients.
The technically more demanding minithoracotomy procedure took longer to perform by a mean of 44 minutes, it prolonged cross-clamp time by 11 minutes, and it required 30 minutes more cardiopulmonary bypass support, Dr. Akowuah reported.
The two patient groups showed no significant differences in the primary endpoint of physical function and ability to return to usual activity levels at 12 weeks, as assessed by scores on the 36-Item Short Form Survey and wrist-worn accelerometer monitoring. At 6 weeks, however, the mini-thoracotomy patients had shown a significant early but temporary advantage for those recovery measures.
The minithoracotomy group clearly fared better, however, on some secondary endpoints. For example, their median hospital LOS was 5 days, compared with 6 days for the sternotomy group (P = .003), and 33.1% of the mini-thoracotomy patients were discharged within 4 days of the surgery, compared with only 15.3% of patients who had the standard procedure (P < .001).
The minithoracotomy group also had marginally more days alive out of the hospital at both 30 days (23.6 days vs. 22.4 days in the sternotomy group) and 90 days (82.7 days and 80.5 days, respectively) after the surgery (P = .03 for both differences).
Safety outcomes at 12 weeks were similar, with no significant differences in rate of death, strokes, MI, or renal impairment, or in ICU length of stay or need for more than 48 hours of mechanical ventilation, Dr. Akowuah reported.
Safety outcomes at 1 year were also similar. Mortality by then was 2.4% for the minithoracotomy patients and 2.5% for the sternotomy group, nor were there significant differences in HHF rates or need for repeat MV surgical repair.
Dr. Akowuah said the patients will be followed for up to 5 years for the primary outcomes, echocardiographic changes, and clinical events.
The minithoracotomy surgery’s longer operative times and specialized equipment make it more a expensive procedure than the standard surgery, he said. “So we need to work out in a cost-effectiveness analysis whether that is offset by the benefits,” such as shorter hospital stays or perhaps fewer transfusions or readmissions.
The study was funded by the United Kingdom’s National Institute for Health and Care Research. Dr. Akowuah reported no relevant financial relationships with industry.
A version of this article first appeared on Medscape.com.
Patients with degenerative mitral valve (MV) regurgitation that calls for surgery may, for the most part, safely choose either a standard procedure requiring a midline sternotomy or one performed through a minithoracotomy, suggests a randomized comparison of the two techniques.
Still, the minimally invasive approach showed some advantages in the study. Patients’ quality of recovery was about the same with both procedures at 12 weeks, but those who had the minimally invasive thoracoscopy-guided surgery had shown greater improvement 6 weeks earlier.
Also in the UK Mini Mitral Trial, hospital length of stay (LOS) was significantly shorter for patients who underwent the mini-thoracotomy procedure, and that group spent fewer days in the hospital over the following months.
But neither procedure had an edge in terms of postoperative clinical risk in the study. Rates of clinical events, such as death or hospitalization for heart failure (HHF), were about the same over 1 year.
Patients in this trial had been deemed suitable for either of the two surgeries, which were always performed by surgeons specially chosen by the steering committee for their experience and expertise.
This first randomized head-to-head comparison of the two approaches in such patients should make both patients and clinicians more confident about choosing the minimally invasive surgery for degenerative MV disease, said Enoch Akowuah, MD, Newcastle (England) University, United Kingdom.
Dr. Akowuah presented the UK Mini-Mitral Trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
A “main takeaway” for clinical practice from the trial would be that minithoracotomy MV repair “is as safe and effective as conventional sternotomy for degenerative mitral regurgitation,” said discussant Amy E. Simone, PA-C, following Dr. Akowuah’s presentation.
“I think this study is unique in that its focus is on delivering high-quality, cost-efficient care for mitral regurgitation, but also with an emphasis on patients’ goals and wishes,” said Ms. Simone, who directs the Marcus Heart Valve Center of the Piedmont Heart Institute, Atlanta.
Cardiac surgeon Thomas MacGillivray, MD, another discussant, agreed that the data presented from at least this study suggest neither the minithoracotomy nor sternotomy approach is better than the other. But he questioned whether that would hold true if applied to broader clinical practice.
Dr. MacGillivray, of MedStar Washington Hospital Center, Washington, observed that only 330 patients were randomly assigned among a total of 1,167 candidates for candidates for MV repair surgery.
Indeed, he noted, more than 200 declined and about 600 were declared ineligible for the study, “even though it had seemed as if all were appropriate for mitral valve repair. That could be viewed as a significant limitation in terms of scalability in the real world.”
Some of those patients weren’t randomly assigned because they ultimately were not considered appropriate for both procedures, and some expressed a preference for one or the other approach, Dr. Akowuah replied. Those were the most common reasons. Many others did not enter the study, he said, because their mitral regurgitation was functional, not degenerative.
The two randomization groups fared similarly for the primary endpoint reflecting recovery from surgery, so the trial was actually “negative,” Dr. Akowuah said in an interview. However, “I see it as very much a win for minithoracotomy. The outstanding questions for clinicians and patients have been about the clinical efficacy and safety of the technique. And we’ve shown in this trial that minithoracotomy is safe and effective.”
If the minithoracotomy procedure is available, he continued, “and it’s just as clinically effective and safe – and we weren’t sure that was the case until we did this trial – and the repair is almost as durable, then why have a sternotomy?”
The researchers assigned 330 patients with degenerative MV disease who were deemed suitable for either type of surgery to undergo the standard operation via sternotomy or the minithoracotomy procedure at 10 centers in the United Kingdom. The steering committee had hand-selected its 28 experienced surgeons, each of whom performed only one of the two surgeries consistently for the trial’s patients.
The technically more demanding minithoracotomy procedure took longer to perform by a mean of 44 minutes, it prolonged cross-clamp time by 11 minutes, and it required 30 minutes more cardiopulmonary bypass support, Dr. Akowuah reported.
The two patient groups showed no significant differences in the primary endpoint of physical function and ability to return to usual activity levels at 12 weeks, as assessed by scores on the 36-Item Short Form Survey and wrist-worn accelerometer monitoring. At 6 weeks, however, the mini-thoracotomy patients had shown a significant early but temporary advantage for those recovery measures.
The minithoracotomy group clearly fared better, however, on some secondary endpoints. For example, their median hospital LOS was 5 days, compared with 6 days for the sternotomy group (P = .003), and 33.1% of the mini-thoracotomy patients were discharged within 4 days of the surgery, compared with only 15.3% of patients who had the standard procedure (P < .001).
The minithoracotomy group also had marginally more days alive out of the hospital at both 30 days (23.6 days vs. 22.4 days in the sternotomy group) and 90 days (82.7 days and 80.5 days, respectively) after the surgery (P = .03 for both differences).
Safety outcomes at 12 weeks were similar, with no significant differences in rate of death, strokes, MI, or renal impairment, or in ICU length of stay or need for more than 48 hours of mechanical ventilation, Dr. Akowuah reported.
Safety outcomes at 1 year were also similar. Mortality by then was 2.4% for the minithoracotomy patients and 2.5% for the sternotomy group, nor were there significant differences in HHF rates or need for repeat MV surgical repair.
Dr. Akowuah said the patients will be followed for up to 5 years for the primary outcomes, echocardiographic changes, and clinical events.
The minithoracotomy surgery’s longer operative times and specialized equipment make it more a expensive procedure than the standard surgery, he said. “So we need to work out in a cost-effectiveness analysis whether that is offset by the benefits,” such as shorter hospital stays or perhaps fewer transfusions or readmissions.
The study was funded by the United Kingdom’s National Institute for Health and Care Research. Dr. Akowuah reported no relevant financial relationships with industry.
A version of this article first appeared on Medscape.com.
FROM ACC 2023
Causal AI quantifies CV risk, providing patient-specific goals
NEW ORLEANS – Causal artificial intelligence (AI) can translate polygenic scores (PGS) and other genetic information into risk reduction strategies for coronary artery disease (CAD) that is tailored for each individual patient, according to an analysis presented at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
Tested for LDL cholesterol (LDL-C) and systolic blood pressure (SBP), causal AI explained how much each of these risk factors must improve at the level of each individual patient “to overcome overall inherited risk,” reported Brian Ference, MD, MPhil, director of translational therapeutics, University of Cambridge (England).
Unlike the “black box” risk assessments common to machine learning, which relies on disparate forms of information of often unknown relative significance, causal AI explains cause and effect. In the case of CAD, its ability to encode the biological causes means that it can “both predict outcomes and prescribe specific actions to change those outcomes,” Dr. Ference explained.
The concept is testable against observed biology using randomized evidence, which was the objective of the study Dr. Ference presented in the late-breaker session.
Causal AI trained on nearly 2 million patients
This study employed a causal AI platform trained on roughly 1.3 million participants in Mendelian randomization studies, as well as more than 500,000 participants in randomized clinical trials. The PGS estimate of inherited risk was constructed from almost 4.1 million variants from genomewide association studies.
To test the ability of causal AI to reveal how much LDL-C or SBP had to be reduced to overcome the inherited risk of CAD based on PGS, it was applied to 445,765 participants of European ancestry in the UK Biobank. The goal was to determine how much those with greater than average risk would need to lower their LDL-C or SBP to achieve average CAD risk.
When validated against observed rates of events, causal AI accurately characterized risk before estimating what reductions in LDL-C, SBP, or both would attenuate that risk.
Providing examples, Dr. Ference explained that a PGS in the 80th percentile can be overcome by lowering LDL-C by 14 mg/dL. Alternatively, the 80th percentile risk could also be overcome by simultaneously lowering LDL-C and SBP by 7 mg/dL and 2.5 mm Hg, respectively.
Required risk factor reductions increase with age because of the increased risk of the events. For example, while a 14.8 mg/dL reduction in LDL-C would be adequate to overcome risk defined by a PGS in the 80th percentile at age 35, reductions of 18.2 mg/dL, 28.9 mg/dL, and 42.6 mg/dL would be required, respectively, at ages 45, 55, and 65 years. The values climb similarly for SBP.
Family history of CAD adds an independent variable that further contributes to the ability of causal AI to estimate risk and the degree of risk factor attenuation to overcome the risk.
Even though family history is equivalent to having PGS above the 95th percentile, it is an independent and additive variable, according to Dr. Ference. As a result, inherited risk of CAD depends on both.
Still when family history is factored into the analysis, “causal AI accurately estimated the magnitude of lower LDL-C, SBP, or both needed to overcome overall inherited risk at all levels of higher or lower PGS,” he reported.
According to Dr. Ference, the value of causal AI is that it can generate very specific goals for each patient regarding modifiable risk factors. Causal effects of risk factors encoded in time units of exposure allow the patient and the clinician to understand the biology and the basis of the disease burden.
Treatments become understandable to patients
“Encoding biology creates algorithms that are deeply explainable because they reveal why a person is at risk, how to reduce that risk, and how much each person will benefit from specific actions to reduce risk,” Dr. Ference said.
A real-world, randomized trial to confirm that the information from causal AI can reduce the risk of CAD is expected to start in 2023, but Dr. Ference thinks that causal AI for managing CAD risk, independent of this planned trial, is essentially inevitable. PGS, which he thinks will be performed routinely in all individuals within 10 years, is only likely to improve. He foresees large advantages of this form of personalized medicine.
Ami Bhatt, MD, chief innovation officer for the American College of Cardiology, Washington, agreed, seeing a direct relationship between precision health as the pathway to improvements in population health.
By explaining risk factors in terms of mechanisms and specific goals to ameliorate these risks, it “engages our patients with agency,” said Dr. Bhatt. She suggested that the information provided by causal AI has the potential to empower patients while creating a collaborative approach with clinicians to CAD prevention.
With patient-specific information provided in the context of the disease biology, “you increase the sense of transparency,” Dr. Bhatt said.
She suggested this direction of research is wholly consistent with initiatives such as those from the World Health Organization to improve precision medicine as a step toward equipping patients to manage their own health.
Dr. Ference reported financial relationships with Amgen, AstraZeneca, CiVi Pharma, Daiichi Sankyo, DalCOR, Esperion, Eli Lilly, Ionis Pharmaceuticals, KrKA, Medicines Company, Merck, Mylan, Novo Nordisk, Novartis, and Sanofi, and Viatris. Dr. Bhatt reported no potential conflicts of interest.
NEW ORLEANS – Causal artificial intelligence (AI) can translate polygenic scores (PGS) and other genetic information into risk reduction strategies for coronary artery disease (CAD) that is tailored for each individual patient, according to an analysis presented at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
Tested for LDL cholesterol (LDL-C) and systolic blood pressure (SBP), causal AI explained how much each of these risk factors must improve at the level of each individual patient “to overcome overall inherited risk,” reported Brian Ference, MD, MPhil, director of translational therapeutics, University of Cambridge (England).
Unlike the “black box” risk assessments common to machine learning, which relies on disparate forms of information of often unknown relative significance, causal AI explains cause and effect. In the case of CAD, its ability to encode the biological causes means that it can “both predict outcomes and prescribe specific actions to change those outcomes,” Dr. Ference explained.
The concept is testable against observed biology using randomized evidence, which was the objective of the study Dr. Ference presented in the late-breaker session.
Causal AI trained on nearly 2 million patients
This study employed a causal AI platform trained on roughly 1.3 million participants in Mendelian randomization studies, as well as more than 500,000 participants in randomized clinical trials. The PGS estimate of inherited risk was constructed from almost 4.1 million variants from genomewide association studies.
To test the ability of causal AI to reveal how much LDL-C or SBP had to be reduced to overcome the inherited risk of CAD based on PGS, it was applied to 445,765 participants of European ancestry in the UK Biobank. The goal was to determine how much those with greater than average risk would need to lower their LDL-C or SBP to achieve average CAD risk.
When validated against observed rates of events, causal AI accurately characterized risk before estimating what reductions in LDL-C, SBP, or both would attenuate that risk.
Providing examples, Dr. Ference explained that a PGS in the 80th percentile can be overcome by lowering LDL-C by 14 mg/dL. Alternatively, the 80th percentile risk could also be overcome by simultaneously lowering LDL-C and SBP by 7 mg/dL and 2.5 mm Hg, respectively.
Required risk factor reductions increase with age because of the increased risk of the events. For example, while a 14.8 mg/dL reduction in LDL-C would be adequate to overcome risk defined by a PGS in the 80th percentile at age 35, reductions of 18.2 mg/dL, 28.9 mg/dL, and 42.6 mg/dL would be required, respectively, at ages 45, 55, and 65 years. The values climb similarly for SBP.
Family history of CAD adds an independent variable that further contributes to the ability of causal AI to estimate risk and the degree of risk factor attenuation to overcome the risk.
Even though family history is equivalent to having PGS above the 95th percentile, it is an independent and additive variable, according to Dr. Ference. As a result, inherited risk of CAD depends on both.
Still when family history is factored into the analysis, “causal AI accurately estimated the magnitude of lower LDL-C, SBP, or both needed to overcome overall inherited risk at all levels of higher or lower PGS,” he reported.
According to Dr. Ference, the value of causal AI is that it can generate very specific goals for each patient regarding modifiable risk factors. Causal effects of risk factors encoded in time units of exposure allow the patient and the clinician to understand the biology and the basis of the disease burden.
Treatments become understandable to patients
“Encoding biology creates algorithms that are deeply explainable because they reveal why a person is at risk, how to reduce that risk, and how much each person will benefit from specific actions to reduce risk,” Dr. Ference said.
A real-world, randomized trial to confirm that the information from causal AI can reduce the risk of CAD is expected to start in 2023, but Dr. Ference thinks that causal AI for managing CAD risk, independent of this planned trial, is essentially inevitable. PGS, which he thinks will be performed routinely in all individuals within 10 years, is only likely to improve. He foresees large advantages of this form of personalized medicine.
Ami Bhatt, MD, chief innovation officer for the American College of Cardiology, Washington, agreed, seeing a direct relationship between precision health as the pathway to improvements in population health.
By explaining risk factors in terms of mechanisms and specific goals to ameliorate these risks, it “engages our patients with agency,” said Dr. Bhatt. She suggested that the information provided by causal AI has the potential to empower patients while creating a collaborative approach with clinicians to CAD prevention.
With patient-specific information provided in the context of the disease biology, “you increase the sense of transparency,” Dr. Bhatt said.
She suggested this direction of research is wholly consistent with initiatives such as those from the World Health Organization to improve precision medicine as a step toward equipping patients to manage their own health.
Dr. Ference reported financial relationships with Amgen, AstraZeneca, CiVi Pharma, Daiichi Sankyo, DalCOR, Esperion, Eli Lilly, Ionis Pharmaceuticals, KrKA, Medicines Company, Merck, Mylan, Novo Nordisk, Novartis, and Sanofi, and Viatris. Dr. Bhatt reported no potential conflicts of interest.
NEW ORLEANS – Causal artificial intelligence (AI) can translate polygenic scores (PGS) and other genetic information into risk reduction strategies for coronary artery disease (CAD) that is tailored for each individual patient, according to an analysis presented at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
Tested for LDL cholesterol (LDL-C) and systolic blood pressure (SBP), causal AI explained how much each of these risk factors must improve at the level of each individual patient “to overcome overall inherited risk,” reported Brian Ference, MD, MPhil, director of translational therapeutics, University of Cambridge (England).
Unlike the “black box” risk assessments common to machine learning, which relies on disparate forms of information of often unknown relative significance, causal AI explains cause and effect. In the case of CAD, its ability to encode the biological causes means that it can “both predict outcomes and prescribe specific actions to change those outcomes,” Dr. Ference explained.
The concept is testable against observed biology using randomized evidence, which was the objective of the study Dr. Ference presented in the late-breaker session.
Causal AI trained on nearly 2 million patients
This study employed a causal AI platform trained on roughly 1.3 million participants in Mendelian randomization studies, as well as more than 500,000 participants in randomized clinical trials. The PGS estimate of inherited risk was constructed from almost 4.1 million variants from genomewide association studies.
To test the ability of causal AI to reveal how much LDL-C or SBP had to be reduced to overcome the inherited risk of CAD based on PGS, it was applied to 445,765 participants of European ancestry in the UK Biobank. The goal was to determine how much those with greater than average risk would need to lower their LDL-C or SBP to achieve average CAD risk.
When validated against observed rates of events, causal AI accurately characterized risk before estimating what reductions in LDL-C, SBP, or both would attenuate that risk.
Providing examples, Dr. Ference explained that a PGS in the 80th percentile can be overcome by lowering LDL-C by 14 mg/dL. Alternatively, the 80th percentile risk could also be overcome by simultaneously lowering LDL-C and SBP by 7 mg/dL and 2.5 mm Hg, respectively.
Required risk factor reductions increase with age because of the increased risk of the events. For example, while a 14.8 mg/dL reduction in LDL-C would be adequate to overcome risk defined by a PGS in the 80th percentile at age 35, reductions of 18.2 mg/dL, 28.9 mg/dL, and 42.6 mg/dL would be required, respectively, at ages 45, 55, and 65 years. The values climb similarly for SBP.
Family history of CAD adds an independent variable that further contributes to the ability of causal AI to estimate risk and the degree of risk factor attenuation to overcome the risk.
Even though family history is equivalent to having PGS above the 95th percentile, it is an independent and additive variable, according to Dr. Ference. As a result, inherited risk of CAD depends on both.
Still when family history is factored into the analysis, “causal AI accurately estimated the magnitude of lower LDL-C, SBP, or both needed to overcome overall inherited risk at all levels of higher or lower PGS,” he reported.
According to Dr. Ference, the value of causal AI is that it can generate very specific goals for each patient regarding modifiable risk factors. Causal effects of risk factors encoded in time units of exposure allow the patient and the clinician to understand the biology and the basis of the disease burden.
Treatments become understandable to patients
“Encoding biology creates algorithms that are deeply explainable because they reveal why a person is at risk, how to reduce that risk, and how much each person will benefit from specific actions to reduce risk,” Dr. Ference said.
A real-world, randomized trial to confirm that the information from causal AI can reduce the risk of CAD is expected to start in 2023, but Dr. Ference thinks that causal AI for managing CAD risk, independent of this planned trial, is essentially inevitable. PGS, which he thinks will be performed routinely in all individuals within 10 years, is only likely to improve. He foresees large advantages of this form of personalized medicine.
Ami Bhatt, MD, chief innovation officer for the American College of Cardiology, Washington, agreed, seeing a direct relationship between precision health as the pathway to improvements in population health.
By explaining risk factors in terms of mechanisms and specific goals to ameliorate these risks, it “engages our patients with agency,” said Dr. Bhatt. She suggested that the information provided by causal AI has the potential to empower patients while creating a collaborative approach with clinicians to CAD prevention.
With patient-specific information provided in the context of the disease biology, “you increase the sense of transparency,” Dr. Bhatt said.
She suggested this direction of research is wholly consistent with initiatives such as those from the World Health Organization to improve precision medicine as a step toward equipping patients to manage their own health.
Dr. Ference reported financial relationships with Amgen, AstraZeneca, CiVi Pharma, Daiichi Sankyo, DalCOR, Esperion, Eli Lilly, Ionis Pharmaceuticals, KrKA, Medicines Company, Merck, Mylan, Novo Nordisk, Novartis, and Sanofi, and Viatris. Dr. Bhatt reported no potential conflicts of interest.
AT ACC 2023
NUDGE-FLU: Electronic ‘nudges’ boost flu shot uptake in seniors
Two types of electronically delivered letter strategies – a letter highlighting potential cardiovascular benefits of influenza vaccination and a repeat reminder letter – increased flu shot uptake, compared with usual care alone, in a national study of seniors in Denmark.
And in a prespecified subanalysis focusing on older adults with cardiovascular disease, these two strategies were also effective in boosting vaccine uptake in those with or without CVD.
The findings are from the Nationwide Utilization of Danish Government Electronic Letter System for Increasing Influenza Vaccine Uptake (NUDGE-FLU) trial, which compared usual care alone with one of nine different electronic letter “behavioral nudge” strategies during the 2022-2023 flu season in people aged 65 years and older. 
Niklas Dyrby Johansen, MD, Hospital–Herlev and Gentofte and Copenhagen University, presented the main study findings in a late-breaking clinical trial session at the joint scientific sessions of the American College of Cardiology and the World Heart Federation, and the article was simultaneously published in The Lancet
The subanalysis in patients with CVD was published online March 5 in Circulation.
“Despite modest effect sizes, the results may have important implications when translated to a population level,” Dr. Dyrby Johansen concluded during his presentation. Still, the authors write, “the low-touch (no person-to-person interaction), inexpensive, and highly scalable nature of these electronic letters might have important population-level public health implications.”
They note that, among approximately 63 million Medicare beneficiaries in the United States, a 0.89–percentage point absolute increase in vaccination rate achieved through the most successful electronic letter in NUDGE-FLU, the one highlighting cardiovascular gain, would be expected to lead to 500,000 additional vaccinations and potentially prevent 7,849 illnesses, 4,395 medical visits, 714 hospitalizations, and 66 deaths each year.
Electronic letter systems similar to the one used in this trial are already in place in several European countries, including Sweden, Norway, and Ireland, the researchers note.
In countries such as the United States, where implementing a nationwide government electronic letter system might not be feasible, nudges could be done via email, text message, or other systems, but whether this would be as effective remains to be seen.
Commenting on the findings, David Cho, MD, UCLA Health and chair of the ACC Health Care Innovation Council, commended the researchers on engaging patients with more than a million separate nudges sent out during one flu season, and randomly assigning participants to 10 different types of nudges, calling it “impressive.”
“I think the concept that the nudge is to plant an idea that leads to an action is pretty much the basis of a lot of these health care interventions, which seems like a small way to have a big impact at outcome,” Dr. Cho noted. “The behavioral science aspects of the nudges are also fascinating to me personally, and I think to a lot of the cardiologists in the audience – about how you actually get people to act. I think it’s been a lifelong question for people in general, how do you get people to follow through on an action?”
“So I found the fact that secondary gain from a cardiovascular health standpoint, but also the repeated nudges were sort of simple ways that you could have people take ownership and get their flu vaccination,” he said.
“This is ACC, this is a cardiovascular conference, but the influence of vaccine is not just a primary care problem, it is also directly affecting cardiovascular disease,” Dr. Cho concluded.
‘Small but important effect’
In an accompanying editorial (Lancet. 2023 Mar 5. doi: 10.1016/S0140-6736(23)00453-1), Melissa Stockwell, MD, Columbia University, New York, writes, “The study by Johansen and colleagues highlights the small but still important effect of scalable, digital interventions across an entire at-risk population.”
A difference of 0.89% in the entire study population of over 960,000 adults age 65 years or older would be more than 8,500 additional adults protected, she notes. “That increase is important for a scalable intervention that has a low cost per letter.”
Moreover, “that the cardiovascular gain–framed messages worked best in those who had not been vaccinated in the previous season further highlights the potential impact on a more vaccine-hesitant population,” Dr. Stockwell notes.
However, with the mandatory government electronic notification system in Denmark, “notifications are sent via regular email and SMS message, and recipients log in through a portal or smartphone app to view the letter.” Similar studies in the United States that included this extra step of needing to sign in online have not been effective in older populations.
Another limitation is that the intervention may have a different effect in populations for which there is a digital divide between people with or without Internet access of sufficient data on their mobile phones.
First-of-its kind, nationwide pragmatic trial
The NUDGE-FLU protocol was previously published in the American Heart Journal. NUDGE-FLU is a first-of-its kind nationwide, pragmatic, registry-based, cluster-randomized implementation trial of electronically delivered nudges to increase influenza vaccination uptake, the researchers note.
They identified 964,870 individuals who were 65 years or older (or would turn 65 by Jan. 15, 2023) who lived in one of 691,820 households in Denmark.
This excluded individuals who lived in a nursing home or were exempt from the government’s mandatory electronic letter system that is used for official communications.
Households were randomly assigned 9:1:1:1:1:1:1:1:1:1 to receive usual care alone or to one of nine electronic letter strategies based on different behavioral science approaches to encourage influenza vaccination uptake:
- Standard electronic letter
- Standard electronic letter sent at randomization and again 14 days later (repeated letter)
- Depersonalized letter without the recipient’s name
- Gain-framing nudge (“Vaccinations help end pandemics, like COVID-19 and the flu. Protect yourself and your loved ones.”)
- Loss-framing nudge (“When too few people get vaccinated, pandemics from diseases like COVID-19 and the flu can spread and place you and your loved ones at risk.”)
- Collective-goal nudge (“78% of Danes 65 and above were vaccinated against influenza last year. Help us achieve an even higher goal this year.”)
- Active choice or implementation-intention prompt (“We encourage you to record your appointment time here.”)
- Cardiovascular gain–framing nudge (“In addition to its protection against influenza infection, influenza vaccination also seems to protect against cardiovascular disease such as heart attacks and heart failure.”)
- Expert-authority statement (“I recommend everyone over the age of 65 years to get vaccinated against influenza – Tyra Grove Krause, Executive Vice President, Statens Serum Institut.”)
The electronic letters were sent out Sept. 16, 2022, and the primary endpoint was vaccine receipt on or before Jan. 1, 2023.
All individuals received an informative vaccination encouragement letter from the Danish Health Authority (usual care) delivered via the same electronic letter system during Sept. 17 through Sept. 21, 2022.
The individuals had a mean age of 73.8 years, 51.5% were women, and 27.4% had chronic cardiovascular disease.
The analyses were done in one randomly selected individual per household.
Influenza vaccination rates were significantly higher in the cardiovascular gain–framing nudge group vs. usual care (81.00% vs. 80.12%; difference, 0.89 percentage points; P < .0001) and in the repeat-letter group vs. usual care (80.85% vs 80.12%; difference, 0.73 percentage points; P = .0006).
These two strategies also improved vaccination rates across major subgroups.
The cardiovascular gain–framed letter was particularly effective among participants who had not been vaccinated for influenza in the previous season.
The seven other letter strategies did not increase flu shot uptake.
Subanalysis in CVD
In the prespecified subanalysis of the NUDGE-FLU trial of patients aged 65 and older that focused on patients with CVD, Daniel Modin, MB, and colleagues report that 83.1% of patients with CVD vs. 79.2% of patients without CVD received influenza vaccination within the requested time (P < .0001).
The two nudging strategies – a letter highlighting potential cardiovascular benefits of influenza vaccination or a repeat letter – that were effective in boosting flu shot rates in the main analysis were also effective in all major CVD subgroups (ischemic heart disease, pulmonary heart disease, heart failure, atrial fibrillation, cerebrovascular disease, atherosclerotic CVD, embolic or thrombotic disease, and congenital heart disease).
Despite strong guideline endorsement, “influenza vaccination rates remain suboptimal in patients with high-risk cardiovascular disease,” Dr. Morin and colleagues write, possibly because of “insufficient knowledge among patients and providers of potential clinical benefits, concerns about vaccine safety, and other forms of vaccine hesitancy.”
Their findings suggest that “select digital behaviorally informed nudges delivered in advance of vaccine availability might be utilized to increase influenza vaccinate uptake in individuals with cardiovascular disease.”
NUDGE-HF was funded by Sanofi. Dr. Johansen and Dr. Modin have no disclosures. The disclosures of the other authors are listed with the articles. Dr. Stockwell has no disclosures.
A version of this article first appeared on Medscape.com.
Two types of electronically delivered letter strategies – a letter highlighting potential cardiovascular benefits of influenza vaccination and a repeat reminder letter – increased flu shot uptake, compared with usual care alone, in a national study of seniors in Denmark.
And in a prespecified subanalysis focusing on older adults with cardiovascular disease, these two strategies were also effective in boosting vaccine uptake in those with or without CVD.
The findings are from the Nationwide Utilization of Danish Government Electronic Letter System for Increasing Influenza Vaccine Uptake (NUDGE-FLU) trial, which compared usual care alone with one of nine different electronic letter “behavioral nudge” strategies during the 2022-2023 flu season in people aged 65 years and older.
Niklas Dyrby Johansen, MD, Hospital–Herlev and Gentofte and Copenhagen University, presented the main study findings in a late-breaking clinical trial session at the joint scientific sessions of the American College of Cardiology and the World Heart Federation, and the article was simultaneously published in The Lancet
The subanalysis in patients with CVD was published online March 5 in Circulation.
“Despite modest effect sizes, the results may have important implications when translated to a population level,” Dr. Dyrby Johansen concluded during his presentation. Still, the authors write, “the low-touch (no person-to-person interaction), inexpensive, and highly scalable nature of these electronic letters might have important population-level public health implications.”
They note that, among approximately 63 million Medicare beneficiaries in the United States, a 0.89–percentage point absolute increase in vaccination rate achieved through the most successful electronic letter in NUDGE-FLU, the one highlighting cardiovascular gain, would be expected to lead to 500,000 additional vaccinations and potentially prevent 7,849 illnesses, 4,395 medical visits, 714 hospitalizations, and 66 deaths each year.
Electronic letter systems similar to the one used in this trial are already in place in several European countries, including Sweden, Norway, and Ireland, the researchers note.
In countries such as the United States, where implementing a nationwide government electronic letter system might not be feasible, nudges could be done via email, text message, or other systems, but whether this would be as effective remains to be seen.
Commenting on the findings, David Cho, MD, UCLA Health and chair of the ACC Health Care Innovation Council, commended the researchers on engaging patients with more than a million separate nudges sent out during one flu season, and randomly assigning participants to 10 different types of nudges, calling it “impressive.”
“I think the concept that the nudge is to plant an idea that leads to an action is pretty much the basis of a lot of these health care interventions, which seems like a small way to have a big impact at outcome,” Dr. Cho noted. “The behavioral science aspects of the nudges are also fascinating to me personally, and I think to a lot of the cardiologists in the audience – about how you actually get people to act. I think it’s been a lifelong question for people in general, how do you get people to follow through on an action?”
“So I found the fact that secondary gain from a cardiovascular health standpoint, but also the repeated nudges were sort of simple ways that you could have people take ownership and get their flu vaccination,” he said.
“This is ACC, this is a cardiovascular conference, but the influence of vaccine is not just a primary care problem, it is also directly affecting cardiovascular disease,” Dr. Cho concluded.
‘Small but important effect’
In an accompanying editorial (Lancet. 2023 Mar 5. doi: 10.1016/S0140-6736(23)00453-1), Melissa Stockwell, MD, Columbia University, New York, writes, “The study by Johansen and colleagues highlights the small but still important effect of scalable, digital interventions across an entire at-risk population.”
A difference of 0.89% in the entire study population of over 960,000 adults age 65 years or older would be more than 8,500 additional adults protected, she notes. “That increase is important for a scalable intervention that has a low cost per letter.”
Moreover, “that the cardiovascular gain–framed messages worked best in those who had not been vaccinated in the previous season further highlights the potential impact on a more vaccine-hesitant population,” Dr. Stockwell notes.
However, with the mandatory government electronic notification system in Denmark, “notifications are sent via regular email and SMS message, and recipients log in through a portal or smartphone app to view the letter.” Similar studies in the United States that included this extra step of needing to sign in online have not been effective in older populations.
Another limitation is that the intervention may have a different effect in populations for which there is a digital divide between people with or without Internet access of sufficient data on their mobile phones.
First-of-its kind, nationwide pragmatic trial
The NUDGE-FLU protocol was previously published in the American Heart Journal. NUDGE-FLU is a first-of-its kind nationwide, pragmatic, registry-based, cluster-randomized implementation trial of electronically delivered nudges to increase influenza vaccination uptake, the researchers note.
They identified 964,870 individuals who were 65 years or older (or would turn 65 by Jan. 15, 2023) who lived in one of 691,820 households in Denmark.
This excluded individuals who lived in a nursing home or were exempt from the government’s mandatory electronic letter system that is used for official communications.
Households were randomly assigned 9:1:1:1:1:1:1:1:1:1 to receive usual care alone or to one of nine electronic letter strategies based on different behavioral science approaches to encourage influenza vaccination uptake:
- Standard electronic letter
- Standard electronic letter sent at randomization and again 14 days later (repeated letter)
- Depersonalized letter without the recipient’s name
- Gain-framing nudge (“Vaccinations help end pandemics, like COVID-19 and the flu. Protect yourself and your loved ones.”)
- Loss-framing nudge (“When too few people get vaccinated, pandemics from diseases like COVID-19 and the flu can spread and place you and your loved ones at risk.”)
- Collective-goal nudge (“78% of Danes 65 and above were vaccinated against influenza last year. Help us achieve an even higher goal this year.”)
- Active choice or implementation-intention prompt (“We encourage you to record your appointment time here.”)
- Cardiovascular gain–framing nudge (“In addition to its protection against influenza infection, influenza vaccination also seems to protect against cardiovascular disease such as heart attacks and heart failure.”)
- Expert-authority statement (“I recommend everyone over the age of 65 years to get vaccinated against influenza – Tyra Grove Krause, Executive Vice President, Statens Serum Institut.”)
The electronic letters were sent out Sept. 16, 2022, and the primary endpoint was vaccine receipt on or before Jan. 1, 2023.
All individuals received an informative vaccination encouragement letter from the Danish Health Authority (usual care) delivered via the same electronic letter system during Sept. 17 through Sept. 21, 2022.
The individuals had a mean age of 73.8 years, 51.5% were women, and 27.4% had chronic cardiovascular disease.
The analyses were done in one randomly selected individual per household.
Influenza vaccination rates were significantly higher in the cardiovascular gain–framing nudge group vs. usual care (81.00% vs. 80.12%; difference, 0.89 percentage points; P < .0001) and in the repeat-letter group vs. usual care (80.85% vs 80.12%; difference, 0.73 percentage points; P = .0006).
These two strategies also improved vaccination rates across major subgroups.
The cardiovascular gain–framed letter was particularly effective among participants who had not been vaccinated for influenza in the previous season.
The seven other letter strategies did not increase flu shot uptake.
Subanalysis in CVD
In the prespecified subanalysis of the NUDGE-FLU trial of patients aged 65 and older that focused on patients with CVD, Daniel Modin, MB, and colleagues report that 83.1% of patients with CVD vs. 79.2% of patients without CVD received influenza vaccination within the requested time (P < .0001).
The two nudging strategies – a letter highlighting potential cardiovascular benefits of influenza vaccination or a repeat letter – that were effective in boosting flu shot rates in the main analysis were also effective in all major CVD subgroups (ischemic heart disease, pulmonary heart disease, heart failure, atrial fibrillation, cerebrovascular disease, atherosclerotic CVD, embolic or thrombotic disease, and congenital heart disease).
Despite strong guideline endorsement, “influenza vaccination rates remain suboptimal in patients with high-risk cardiovascular disease,” Dr. Morin and colleagues write, possibly because of “insufficient knowledge among patients and providers of potential clinical benefits, concerns about vaccine safety, and other forms of vaccine hesitancy.”
Their findings suggest that “select digital behaviorally informed nudges delivered in advance of vaccine availability might be utilized to increase influenza vaccinate uptake in individuals with cardiovascular disease.”
NUDGE-HF was funded by Sanofi. Dr. Johansen and Dr. Modin have no disclosures. The disclosures of the other authors are listed with the articles. Dr. Stockwell has no disclosures.
A version of this article first appeared on Medscape.com.
Two types of electronically delivered letter strategies – a letter highlighting potential cardiovascular benefits of influenza vaccination and a repeat reminder letter – increased flu shot uptake, compared with usual care alone, in a national study of seniors in Denmark.
And in a prespecified subanalysis focusing on older adults with cardiovascular disease, these two strategies were also effective in boosting vaccine uptake in those with or without CVD.
The findings are from the Nationwide Utilization of Danish Government Electronic Letter System for Increasing Influenza Vaccine Uptake (NUDGE-FLU) trial, which compared usual care alone with one of nine different electronic letter “behavioral nudge” strategies during the 2022-2023 flu season in people aged 65 years and older.
Niklas Dyrby Johansen, MD, Hospital–Herlev and Gentofte and Copenhagen University, presented the main study findings in a late-breaking clinical trial session at the joint scientific sessions of the American College of Cardiology and the World Heart Federation, and the article was simultaneously published in The Lancet
The subanalysis in patients with CVD was published online March 5 in Circulation.
“Despite modest effect sizes, the results may have important implications when translated to a population level,” Dr. Dyrby Johansen concluded during his presentation. Still, the authors write, “the low-touch (no person-to-person interaction), inexpensive, and highly scalable nature of these electronic letters might have important population-level public health implications.”
They note that, among approximately 63 million Medicare beneficiaries in the United States, a 0.89–percentage point absolute increase in vaccination rate achieved through the most successful electronic letter in NUDGE-FLU, the one highlighting cardiovascular gain, would be expected to lead to 500,000 additional vaccinations and potentially prevent 7,849 illnesses, 4,395 medical visits, 714 hospitalizations, and 66 deaths each year.
Electronic letter systems similar to the one used in this trial are already in place in several European countries, including Sweden, Norway, and Ireland, the researchers note.
In countries such as the United States, where implementing a nationwide government electronic letter system might not be feasible, nudges could be done via email, text message, or other systems, but whether this would be as effective remains to be seen.
Commenting on the findings, David Cho, MD, UCLA Health and chair of the ACC Health Care Innovation Council, commended the researchers on engaging patients with more than a million separate nudges sent out during one flu season, and randomly assigning participants to 10 different types of nudges, calling it “impressive.”
“I think the concept that the nudge is to plant an idea that leads to an action is pretty much the basis of a lot of these health care interventions, which seems like a small way to have a big impact at outcome,” Dr. Cho noted. “The behavioral science aspects of the nudges are also fascinating to me personally, and I think to a lot of the cardiologists in the audience – about how you actually get people to act. I think it’s been a lifelong question for people in general, how do you get people to follow through on an action?”
“So I found the fact that secondary gain from a cardiovascular health standpoint, but also the repeated nudges were sort of simple ways that you could have people take ownership and get their flu vaccination,” he said.
“This is ACC, this is a cardiovascular conference, but the influence of vaccine is not just a primary care problem, it is also directly affecting cardiovascular disease,” Dr. Cho concluded.
‘Small but important effect’
In an accompanying editorial (Lancet. 2023 Mar 5. doi: 10.1016/S0140-6736(23)00453-1), Melissa Stockwell, MD, Columbia University, New York, writes, “The study by Johansen and colleagues highlights the small but still important effect of scalable, digital interventions across an entire at-risk population.”
A difference of 0.89% in the entire study population of over 960,000 adults age 65 years or older would be more than 8,500 additional adults protected, she notes. “That increase is important for a scalable intervention that has a low cost per letter.”
Moreover, “that the cardiovascular gain–framed messages worked best in those who had not been vaccinated in the previous season further highlights the potential impact on a more vaccine-hesitant population,” Dr. Stockwell notes.
However, with the mandatory government electronic notification system in Denmark, “notifications are sent via regular email and SMS message, and recipients log in through a portal or smartphone app to view the letter.” Similar studies in the United States that included this extra step of needing to sign in online have not been effective in older populations.
Another limitation is that the intervention may have a different effect in populations for which there is a digital divide between people with or without Internet access of sufficient data on their mobile phones.
First-of-its kind, nationwide pragmatic trial
The NUDGE-FLU protocol was previously published in the American Heart Journal. NUDGE-FLU is a first-of-its kind nationwide, pragmatic, registry-based, cluster-randomized implementation trial of electronically delivered nudges to increase influenza vaccination uptake, the researchers note.
They identified 964,870 individuals who were 65 years or older (or would turn 65 by Jan. 15, 2023) who lived in one of 691,820 households in Denmark.
This excluded individuals who lived in a nursing home or were exempt from the government’s mandatory electronic letter system that is used for official communications.
Households were randomly assigned 9:1:1:1:1:1:1:1:1:1 to receive usual care alone or to one of nine electronic letter strategies based on different behavioral science approaches to encourage influenza vaccination uptake:
- Standard electronic letter
- Standard electronic letter sent at randomization and again 14 days later (repeated letter)
- Depersonalized letter without the recipient’s name
- Gain-framing nudge (“Vaccinations help end pandemics, like COVID-19 and the flu. Protect yourself and your loved ones.”)
- Loss-framing nudge (“When too few people get vaccinated, pandemics from diseases like COVID-19 and the flu can spread and place you and your loved ones at risk.”)
- Collective-goal nudge (“78% of Danes 65 and above were vaccinated against influenza last year. Help us achieve an even higher goal this year.”)
- Active choice or implementation-intention prompt (“We encourage you to record your appointment time here.”)
- Cardiovascular gain–framing nudge (“In addition to its protection against influenza infection, influenza vaccination also seems to protect against cardiovascular disease such as heart attacks and heart failure.”)
- Expert-authority statement (“I recommend everyone over the age of 65 years to get vaccinated against influenza – Tyra Grove Krause, Executive Vice President, Statens Serum Institut.”)
The electronic letters were sent out Sept. 16, 2022, and the primary endpoint was vaccine receipt on or before Jan. 1, 2023.
All individuals received an informative vaccination encouragement letter from the Danish Health Authority (usual care) delivered via the same electronic letter system during Sept. 17 through Sept. 21, 2022.
The individuals had a mean age of 73.8 years, 51.5% were women, and 27.4% had chronic cardiovascular disease.
The analyses were done in one randomly selected individual per household.
Influenza vaccination rates were significantly higher in the cardiovascular gain–framing nudge group vs. usual care (81.00% vs. 80.12%; difference, 0.89 percentage points; P < .0001) and in the repeat-letter group vs. usual care (80.85% vs 80.12%; difference, 0.73 percentage points; P = .0006).
These two strategies also improved vaccination rates across major subgroups.
The cardiovascular gain–framed letter was particularly effective among participants who had not been vaccinated for influenza in the previous season.
The seven other letter strategies did not increase flu shot uptake.
Subanalysis in CVD
In the prespecified subanalysis of the NUDGE-FLU trial of patients aged 65 and older that focused on patients with CVD, Daniel Modin, MB, and colleagues report that 83.1% of patients with CVD vs. 79.2% of patients without CVD received influenza vaccination within the requested time (P < .0001).
The two nudging strategies – a letter highlighting potential cardiovascular benefits of influenza vaccination or a repeat letter – that were effective in boosting flu shot rates in the main analysis were also effective in all major CVD subgroups (ischemic heart disease, pulmonary heart disease, heart failure, atrial fibrillation, cerebrovascular disease, atherosclerotic CVD, embolic or thrombotic disease, and congenital heart disease).
Despite strong guideline endorsement, “influenza vaccination rates remain suboptimal in patients with high-risk cardiovascular disease,” Dr. Morin and colleagues write, possibly because of “insufficient knowledge among patients and providers of potential clinical benefits, concerns about vaccine safety, and other forms of vaccine hesitancy.”
Their findings suggest that “select digital behaviorally informed nudges delivered in advance of vaccine availability might be utilized to increase influenza vaccinate uptake in individuals with cardiovascular disease.”
NUDGE-HF was funded by Sanofi. Dr. Johansen and Dr. Modin have no disclosures. The disclosures of the other authors are listed with the articles. Dr. Stockwell has no disclosures.
A version of this article first appeared on Medscape.com.
FROM ACC 2023
EHR alerts boosted MRA prescribing to patients with HFrEF
NEW ORLEANS – EHR-embedded alerts that a patient with heart failure with reduced ejection fraction (HFrEF) is a great candidate for treatment with a mineralocorticoid receptor antagonist (MRA) more than doubled prescribing of this “pillar” class for HFrEF, compared with control practices that used usual care and no alerts.
That’s according to results of BETTER CARE-HF, a single-center, randomized trial with more than 2,000 patients and involving 180 cardiologists.
“EHR-embedded tools cans be a rapid, low-cost, and high-impact method to increase prescription of life-saving therapies across large populations,” said Amrita Mukhopadhyay, MD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
Her study targeted underprescribing of an MRA – spironolactone or eplerenone (Inspra) – because of its “vastly underprescribed” status in U.S. practice, where roughly two-thirds of patients with HFrEF do not receive an MRA despite clear recommendations from several medical groups that it is an essential part of treatment for most patients with HFrEF. Dr. Mukhopadhyay estimated that more comprehensive prescribing of MRAs to U.S. patients with HFrEF could prevent more than 20,000 deaths annually.
She also explained that the EHR-embedded alert was carefully devised, through interviews with cardiologists and pilot testing, to optimize the nudge so that it was less intrusive but effective for capturing attention and initiating action.
‘Clinically relevant, impressive results’
“This is a really important study, because despite overwhelming evidence for more than a decade favoring MRA use for patients with HFrEF there is an incredibly large treatment gap. MRAs can reduce all-cause death in people with HFrEF by 25%-30%, as well as reduce hospitalizations for heart failure, at a cost of less than $50 a year,” commented Gregg C. Fonarow, MD, interim chief of cardiology at the University of California, Los Angeles. The study showed “very clinically relevant, impressive results” for individualized, patient-specific alerts to prescribe an MRA and order the laboratory tests, particularly for serum potassium levels, needed to safely start the treatment, Dr. Fonarow said in an interview.
The BETTER CARE-HF study ran at more than 60 practices in the New York City region operated by the NYU Langone Health system, which sponsored the study. The trial randomized 180 cardiologists from these practices in a cluster format to one of three study arms: Sixty cardiologists received the EHR-embedded alerts for their relevant patients (755 patients) when the patient was in the physician’s office; another 60 cardiologists received a less tailored, monthly message that flagged all patients with HFrEF in a cardiologist’s practice who remained untreated candidates for MRA intervention (812 patients); and a third arm of 60 cardiologists and their HFrEF patients served as controls where the clinicians received no alert or message (644 patients).
The study included 2,211 patients with HFrEF and not on MRA treatment at baseline who were all identified as good candidates for starting treatment with the class, with no contraindications, no preexisting hyperkalemia, and no advanced-stage renal dysfunction.
The study’s primary outcome was the percentage of patients in each subgroup who received a new prescription for an MRA. This occurred in 29.6% of the patients whose physicians received an alert, in 15.6% of the patients whose physicians received a monthly message, and in 11.7% of patients in the control practices. Statistical analyses showed that the alerts led to a significant 2.53-fold increase in MRA prescribing, while the messages linked with a significant 67% increase in prescribing, compared with the control practices, reported Dr. Mukhopadhyay, a health services researcher at NYU Langone Health in New York. Simultaneously with her report, the results also appeared in the Journal of the American College of Cardiology.
The findings also showed that the alert and message had no significant impact on the prescribing of any other medication classes for HFrEF, compared with the controls. And the alert intervention had minimal adverse effects. While patients in the alert arm showed a significant, 45% relative increase in the incidence of hyperkalemia episodes, compared with control patients (because of a 4.5% absolute increase in hyperkalemia events), the rate of “significant” hyperkalemia with a value of at least 5.5 mmol/L, occurred in 5.0% of patients in the alert group and 5.1% of patients in the control arm.
Potassium testing poses another barrier
Even though the alerts substantially improved MRA prescribing, 70% of patients deemed MRA eligible in the alert subgroup still failed to receive a prescription. One additional barrier specific to MRA prescribing is the need it triggers for serial laboratory testing to monitor serum potassium levels. “Potassium testing generates additional work outside the index visit, which along with the risk for hyperkalemia exists as a barrier,” commented Lee R. Goldberg, MD, a heart failure specialist and professor at the University of Pennsylvania in Philadelphia. “This may be the next aspect to focus on to improve MRA uptake,” he said as a designated discussant for the report.
“It’s not enough to just prompt medication treatment. We also need to prompt appropriate laboratory testing,” noted Dr. Fonarow.
He also said that the approach tested by Dr. Mukhopadhyay could now be expanded to outpatient cardiologists. “The onus is on everyone involved in caring for patients with HFrEF failure to explain why maximum effort is not being made to deploy” all of the guideline-directed medical therapies for the disorder.
EHR alerts “are one way to bridge the prescribing gap, but we need multiple approaches so that all eligible patients receive guideline-directed medical therapy,” Dr. Fonarow said.
BETTER CARE-HF received no commercial funding, and Dr. Mukhopadhyay had no disclosures. Dr. Fonarow has been a consultant to AstraZeneca, Amgen, Cytokinetics, Lilly, Merck, Novartis, and Pfizer. Dr. Goldberg has received personal fees from Abbott, VisCardia, and Zoll/Respircardia.
NEW ORLEANS – EHR-embedded alerts that a patient with heart failure with reduced ejection fraction (HFrEF) is a great candidate for treatment with a mineralocorticoid receptor antagonist (MRA) more than doubled prescribing of this “pillar” class for HFrEF, compared with control practices that used usual care and no alerts.
That’s according to results of BETTER CARE-HF, a single-center, randomized trial with more than 2,000 patients and involving 180 cardiologists.
“EHR-embedded tools cans be a rapid, low-cost, and high-impact method to increase prescription of life-saving therapies across large populations,” said Amrita Mukhopadhyay, MD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
Her study targeted underprescribing of an MRA – spironolactone or eplerenone (Inspra) – because of its “vastly underprescribed” status in U.S. practice, where roughly two-thirds of patients with HFrEF do not receive an MRA despite clear recommendations from several medical groups that it is an essential part of treatment for most patients with HFrEF. Dr. Mukhopadhyay estimated that more comprehensive prescribing of MRAs to U.S. patients with HFrEF could prevent more than 20,000 deaths annually.
She also explained that the EHR-embedded alert was carefully devised, through interviews with cardiologists and pilot testing, to optimize the nudge so that it was less intrusive but effective for capturing attention and initiating action.
‘Clinically relevant, impressive results’
“This is a really important study, because despite overwhelming evidence for more than a decade favoring MRA use for patients with HFrEF there is an incredibly large treatment gap. MRAs can reduce all-cause death in people with HFrEF by 25%-30%, as well as reduce hospitalizations for heart failure, at a cost of less than $50 a year,” commented Gregg C. Fonarow, MD, interim chief of cardiology at the University of California, Los Angeles. The study showed “very clinically relevant, impressive results” for individualized, patient-specific alerts to prescribe an MRA and order the laboratory tests, particularly for serum potassium levels, needed to safely start the treatment, Dr. Fonarow said in an interview.
The BETTER CARE-HF study ran at more than 60 practices in the New York City region operated by the NYU Langone Health system, which sponsored the study. The trial randomized 180 cardiologists from these practices in a cluster format to one of three study arms: Sixty cardiologists received the EHR-embedded alerts for their relevant patients (755 patients) when the patient was in the physician’s office; another 60 cardiologists received a less tailored, monthly message that flagged all patients with HFrEF in a cardiologist’s practice who remained untreated candidates for MRA intervention (812 patients); and a third arm of 60 cardiologists and their HFrEF patients served as controls where the clinicians received no alert or message (644 patients).
The study included 2,211 patients with HFrEF and not on MRA treatment at baseline who were all identified as good candidates for starting treatment with the class, with no contraindications, no preexisting hyperkalemia, and no advanced-stage renal dysfunction.
The study’s primary outcome was the percentage of patients in each subgroup who received a new prescription for an MRA. This occurred in 29.6% of the patients whose physicians received an alert, in 15.6% of the patients whose physicians received a monthly message, and in 11.7% of patients in the control practices. Statistical analyses showed that the alerts led to a significant 2.53-fold increase in MRA prescribing, while the messages linked with a significant 67% increase in prescribing, compared with the control practices, reported Dr. Mukhopadhyay, a health services researcher at NYU Langone Health in New York. Simultaneously with her report, the results also appeared in the Journal of the American College of Cardiology.
The findings also showed that the alert and message had no significant impact on the prescribing of any other medication classes for HFrEF, compared with the controls. And the alert intervention had minimal adverse effects. While patients in the alert arm showed a significant, 45% relative increase in the incidence of hyperkalemia episodes, compared with control patients (because of a 4.5% absolute increase in hyperkalemia events), the rate of “significant” hyperkalemia with a value of at least 5.5 mmol/L, occurred in 5.0% of patients in the alert group and 5.1% of patients in the control arm.
Potassium testing poses another barrier
Even though the alerts substantially improved MRA prescribing, 70% of patients deemed MRA eligible in the alert subgroup still failed to receive a prescription. One additional barrier specific to MRA prescribing is the need it triggers for serial laboratory testing to monitor serum potassium levels. “Potassium testing generates additional work outside the index visit, which along with the risk for hyperkalemia exists as a barrier,” commented Lee R. Goldberg, MD, a heart failure specialist and professor at the University of Pennsylvania in Philadelphia. “This may be the next aspect to focus on to improve MRA uptake,” he said as a designated discussant for the report.
“It’s not enough to just prompt medication treatment. We also need to prompt appropriate laboratory testing,” noted Dr. Fonarow.
He also said that the approach tested by Dr. Mukhopadhyay could now be expanded to outpatient cardiologists. “The onus is on everyone involved in caring for patients with HFrEF failure to explain why maximum effort is not being made to deploy” all of the guideline-directed medical therapies for the disorder.
EHR alerts “are one way to bridge the prescribing gap, but we need multiple approaches so that all eligible patients receive guideline-directed medical therapy,” Dr. Fonarow said.
BETTER CARE-HF received no commercial funding, and Dr. Mukhopadhyay had no disclosures. Dr. Fonarow has been a consultant to AstraZeneca, Amgen, Cytokinetics, Lilly, Merck, Novartis, and Pfizer. Dr. Goldberg has received personal fees from Abbott, VisCardia, and Zoll/Respircardia.
NEW ORLEANS – EHR-embedded alerts that a patient with heart failure with reduced ejection fraction (HFrEF) is a great candidate for treatment with a mineralocorticoid receptor antagonist (MRA) more than doubled prescribing of this “pillar” class for HFrEF, compared with control practices that used usual care and no alerts.
That’s according to results of BETTER CARE-HF, a single-center, randomized trial with more than 2,000 patients and involving 180 cardiologists.
“EHR-embedded tools cans be a rapid, low-cost, and high-impact method to increase prescription of life-saving therapies across large populations,” said Amrita Mukhopadhyay, MD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
Her study targeted underprescribing of an MRA – spironolactone or eplerenone (Inspra) – because of its “vastly underprescribed” status in U.S. practice, where roughly two-thirds of patients with HFrEF do not receive an MRA despite clear recommendations from several medical groups that it is an essential part of treatment for most patients with HFrEF. Dr. Mukhopadhyay estimated that more comprehensive prescribing of MRAs to U.S. patients with HFrEF could prevent more than 20,000 deaths annually.
She also explained that the EHR-embedded alert was carefully devised, through interviews with cardiologists and pilot testing, to optimize the nudge so that it was less intrusive but effective for capturing attention and initiating action.
‘Clinically relevant, impressive results’
“This is a really important study, because despite overwhelming evidence for more than a decade favoring MRA use for patients with HFrEF there is an incredibly large treatment gap. MRAs can reduce all-cause death in people with HFrEF by 25%-30%, as well as reduce hospitalizations for heart failure, at a cost of less than $50 a year,” commented Gregg C. Fonarow, MD, interim chief of cardiology at the University of California, Los Angeles. The study showed “very clinically relevant, impressive results” for individualized, patient-specific alerts to prescribe an MRA and order the laboratory tests, particularly for serum potassium levels, needed to safely start the treatment, Dr. Fonarow said in an interview.
The BETTER CARE-HF study ran at more than 60 practices in the New York City region operated by the NYU Langone Health system, which sponsored the study. The trial randomized 180 cardiologists from these practices in a cluster format to one of three study arms: Sixty cardiologists received the EHR-embedded alerts for their relevant patients (755 patients) when the patient was in the physician’s office; another 60 cardiologists received a less tailored, monthly message that flagged all patients with HFrEF in a cardiologist’s practice who remained untreated candidates for MRA intervention (812 patients); and a third arm of 60 cardiologists and their HFrEF patients served as controls where the clinicians received no alert or message (644 patients).
The study included 2,211 patients with HFrEF and not on MRA treatment at baseline who were all identified as good candidates for starting treatment with the class, with no contraindications, no preexisting hyperkalemia, and no advanced-stage renal dysfunction.
The study’s primary outcome was the percentage of patients in each subgroup who received a new prescription for an MRA. This occurred in 29.6% of the patients whose physicians received an alert, in 15.6% of the patients whose physicians received a monthly message, and in 11.7% of patients in the control practices. Statistical analyses showed that the alerts led to a significant 2.53-fold increase in MRA prescribing, while the messages linked with a significant 67% increase in prescribing, compared with the control practices, reported Dr. Mukhopadhyay, a health services researcher at NYU Langone Health in New York. Simultaneously with her report, the results also appeared in the Journal of the American College of Cardiology.
The findings also showed that the alert and message had no significant impact on the prescribing of any other medication classes for HFrEF, compared with the controls. And the alert intervention had minimal adverse effects. While patients in the alert arm showed a significant, 45% relative increase in the incidence of hyperkalemia episodes, compared with control patients (because of a 4.5% absolute increase in hyperkalemia events), the rate of “significant” hyperkalemia with a value of at least 5.5 mmol/L, occurred in 5.0% of patients in the alert group and 5.1% of patients in the control arm.
Potassium testing poses another barrier
Even though the alerts substantially improved MRA prescribing, 70% of patients deemed MRA eligible in the alert subgroup still failed to receive a prescription. One additional barrier specific to MRA prescribing is the need it triggers for serial laboratory testing to monitor serum potassium levels. “Potassium testing generates additional work outside the index visit, which along with the risk for hyperkalemia exists as a barrier,” commented Lee R. Goldberg, MD, a heart failure specialist and professor at the University of Pennsylvania in Philadelphia. “This may be the next aspect to focus on to improve MRA uptake,” he said as a designated discussant for the report.
“It’s not enough to just prompt medication treatment. We also need to prompt appropriate laboratory testing,” noted Dr. Fonarow.
He also said that the approach tested by Dr. Mukhopadhyay could now be expanded to outpatient cardiologists. “The onus is on everyone involved in caring for patients with HFrEF failure to explain why maximum effort is not being made to deploy” all of the guideline-directed medical therapies for the disorder.
EHR alerts “are one way to bridge the prescribing gap, but we need multiple approaches so that all eligible patients receive guideline-directed medical therapy,” Dr. Fonarow said.
BETTER CARE-HF received no commercial funding, and Dr. Mukhopadhyay had no disclosures. Dr. Fonarow has been a consultant to AstraZeneca, Amgen, Cytokinetics, Lilly, Merck, Novartis, and Pfizer. Dr. Goldberg has received personal fees from Abbott, VisCardia, and Zoll/Respircardia.
AT ACC 2023
BIOVASC: Immediate complete revascularization beneficial in ACS
Immediate complete revascularization during the index procedure might become the new treatment paradigm in patients with an acute coronary syndrome (ACS) and multivessel disease, based on results of the BIOVASC trial.
In the trial, in patients presenting with ACS and multivessel disease, immediate complete revascularization was noninferior to staged complete revascularization for the primary composite outcome and was associated with a reduction in myocardial infarction and unplanned ischemia-driven revascularization.
The BIOVASC trial was presented on March 5 by Roberto Diletti, MD, Erasmus University Medical Center, Rotterdam, the Netherlands, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The study was simultaneously published online in The Lancet.
“We did not detect an early safety signal against an immediate complete revascularization strategy,” the authors state in the Lancet paper, adding: “Treating physicians should not be concerned about potential risks associated with immediate treatment of nonculprit lesions.”
They note, “This strategy might be particularly effective in patients with only two-vessel disease and reasonably simple lesions, with a high likelihood of procedural success without excessive use of radiation, contrast dye, or other resources.”
The trial also showed a shorter hospital stay with an immediate complete revascularization strategy.
“Immediate complete revascularization might have potential health economic benefits because of the lower rate of myocardial infarction, including spontaneous myocardial infarction, and unplanned revascularizations, and the shorter overall hospital stay,” the researchers conclude.
Introducing his presentation, Dr. Diletti explained that multiple studies have established the clinical benefit of complete coronary revascularization as compared with exclusive reperfusion of the culprit lesion, but the optimal timing for nonculprit lesion revascularization remains unclear.
The BIOVASC trial, conducted in Belgium, Italy, the Netherlands, and Spain, involved 1,525 patients with ST-segment elevation MI (STEMI) or non-STEMI ACS and multivessel coronary artery disease with a clearly identifiable culprit lesion.
They were randomly assigned to undergo immediate complete revascularization (percutaneous coronary intervention [PCI] of the culprit lesion first, followed by other nonculprit lesions deemed to be clinically significant by the operator during the index procedure) or staged complete revascularization (PCI of only the culprit lesion during the index procedure and PCI of all nonculprit lesions deemed to be clinically significant within 6 weeks after the index procedure).
The primary outcome was the composite of all-cause mortality, MI, any unplanned ischemia-driven revascularization, or cerebrovascular events at 1 year after the index procedure.
The trial had a noninferiority design, with noninferiority of immediate to staged complete revascularization considered to be met if the upper boundary of the 95% confidence interval of the hazard ratio for the primary outcome did not exceed 1.39.
Among the trial population, 40% of patients had STEMI, 52% had non-STEMI, and 8% had unstable angina.
In the immediate complete revascularization group, 16 patients did not receive complete revascularization during the index procedure primarily because of prolonged procedure time, procedural complexity, or excessive contrast dye use.
In the staged group, 30% of patients underwent all subsequent procedures during the index hospitalization.
Results showed that the primary composite outcome at 1 year occurred in 7.6% of the immediate revascularization group and in 9.4% of the staged group, meeting the noninferiority criteria (HR, 0.78; 95% CI, 0.55-1.11; P for noninferiority = .0011).
Superiority of the immediate over the staged complete revascularization strategy was not met at 1-year follow-up (P for superiority = .17).
However, in the prespecified analysis of clinical events at 30 days after the index procedure, immediate complete revascularization was superior to staged revascularization in terms of the composite primary outcome (2.2% vs. 5.8%; HR, 0.38; P for superiority = .0007).
One-year results showed no difference in all-cause death between the two groups, but the immediate complete revascularization group appeared to have a reduction in MI (1.9% vs. 4.5%) and fewer unplanned ischemia-driven revascularizations (4.2% vs. 6.7%).
The difference in MI was mainly driven by spontaneous MIs (not procedure related) that predominantly occurred in the time window between the index procedure and the planned date for the staged intervention, and an originally nonculprit lesion was identified as the cause for these events in almost all cases.
Subgroup analysis showed similar results across the patient population, including age, sex, and STEMI vs. non-STEMI presentation.
High rate of MI in staged group
Discussant of the study at the ACC session, Dipti Itchhaporia, MD, University of California, Irvine, said this was a “very important trial.”
She expressed surprise over the “remarkably high rate” of MI in the staged procedure group and asked Dr. Diletti why that might have occurred.
He responded that the operator may have misjudged the culprit lesion or that patients with ACS may have multiple unstable plaques and “treating the culprit lesion alone does not do the job.”
He added: “We need to look at the data more thoroughly to better understand this, but in both scenarios, immediate complete revascularization would prevent these events.”
Dr. Itchhaporia also pointed out a low rate of functional imaging used in the study.
Dr. Diletti replied that this reflected current European practice, but he acknowledged that, “in my opinion this reduces our ability to detect the culprit lesion.”
Commenting at an ACC press conference, David Moliterno, MD, Gill Heart and Vascular Institute, Lexington, Ky., said the trial poses the question “Can we fix it all at once?” and the results suggest “Yes, we can.”
He said this approach had the advantage of removing any uncertainly as to which was the culprit lesion. “We just fix everything – leave no blockage behind.”
But he pointed out that for some patients this may not be appropriate, such as those with compromised renal function, in whom excessive amounts of contrast material should be avoided.
CABG still needs to be considered
In a comment accompanying the Lancet publication, Tobias Pustjens, MD, Pieter Vriesendorp, MD, and Arnoud W.J. van’t Hof, MD, Cardiovascular Research Institute Maastricht (the Netherlands), note that more than half of the patients presenting with an ACS have multivessel coronary disease.
They say the trial results suggest that “pursuing an immediate complete revascularisation strategy, especially in times of reduced hospital capacity and staff scarcity, not only benefits the individual patient in clinical outcomes but can also safely reduce the pressure on health care systems.”
But they also point out that the possibility of coronary artery bypass grafting (CABG) should not be omitted, and that CABG is still the treatment of choice in patients with diabetes or complex coronary artery disease.
They conclude: “The results of the BIOVASC study move clinical practice forward from culprit-only to an immediate, complete revascularisation strategy. … However, further fine tuning of this treatment strategy to substantiate a role for intracoronary physiology assessment, intracoronary imaging, and guidance of the heart team decision is needed.”
The BIOVASC trial was supported by an unrestricted research grant from Biotronik AG. Dr. Diletti has received institutional research grants from Biotronik, Medtronic, ACIST Medical Systems, and Boston Scientific. Dr. van’t Hof has received institutional research grants from Biotronik.
A version of this article first appeared on Medscape.com.
Immediate complete revascularization during the index procedure might become the new treatment paradigm in patients with an acute coronary syndrome (ACS) and multivessel disease, based on results of the BIOVASC trial.
In the trial, in patients presenting with ACS and multivessel disease, immediate complete revascularization was noninferior to staged complete revascularization for the primary composite outcome and was associated with a reduction in myocardial infarction and unplanned ischemia-driven revascularization.
The BIOVASC trial was presented on March 5 by Roberto Diletti, MD, Erasmus University Medical Center, Rotterdam, the Netherlands, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The study was simultaneously published online in The Lancet.
“We did not detect an early safety signal against an immediate complete revascularization strategy,” the authors state in the Lancet paper, adding: “Treating physicians should not be concerned about potential risks associated with immediate treatment of nonculprit lesions.”
They note, “This strategy might be particularly effective in patients with only two-vessel disease and reasonably simple lesions, with a high likelihood of procedural success without excessive use of radiation, contrast dye, or other resources.”
The trial also showed a shorter hospital stay with an immediate complete revascularization strategy.
“Immediate complete revascularization might have potential health economic benefits because of the lower rate of myocardial infarction, including spontaneous myocardial infarction, and unplanned revascularizations, and the shorter overall hospital stay,” the researchers conclude.
Introducing his presentation, Dr. Diletti explained that multiple studies have established the clinical benefit of complete coronary revascularization as compared with exclusive reperfusion of the culprit lesion, but the optimal timing for nonculprit lesion revascularization remains unclear.
The BIOVASC trial, conducted in Belgium, Italy, the Netherlands, and Spain, involved 1,525 patients with ST-segment elevation MI (STEMI) or non-STEMI ACS and multivessel coronary artery disease with a clearly identifiable culprit lesion.
They were randomly assigned to undergo immediate complete revascularization (percutaneous coronary intervention [PCI] of the culprit lesion first, followed by other nonculprit lesions deemed to be clinically significant by the operator during the index procedure) or staged complete revascularization (PCI of only the culprit lesion during the index procedure and PCI of all nonculprit lesions deemed to be clinically significant within 6 weeks after the index procedure).
The primary outcome was the composite of all-cause mortality, MI, any unplanned ischemia-driven revascularization, or cerebrovascular events at 1 year after the index procedure.
The trial had a noninferiority design, with noninferiority of immediate to staged complete revascularization considered to be met if the upper boundary of the 95% confidence interval of the hazard ratio for the primary outcome did not exceed 1.39.
Among the trial population, 40% of patients had STEMI, 52% had non-STEMI, and 8% had unstable angina.
In the immediate complete revascularization group, 16 patients did not receive complete revascularization during the index procedure primarily because of prolonged procedure time, procedural complexity, or excessive contrast dye use.
In the staged group, 30% of patients underwent all subsequent procedures during the index hospitalization.
Results showed that the primary composite outcome at 1 year occurred in 7.6% of the immediate revascularization group and in 9.4% of the staged group, meeting the noninferiority criteria (HR, 0.78; 95% CI, 0.55-1.11; P for noninferiority = .0011).
Superiority of the immediate over the staged complete revascularization strategy was not met at 1-year follow-up (P for superiority = .17).
However, in the prespecified analysis of clinical events at 30 days after the index procedure, immediate complete revascularization was superior to staged revascularization in terms of the composite primary outcome (2.2% vs. 5.8%; HR, 0.38; P for superiority = .0007).
One-year results showed no difference in all-cause death between the two groups, but the immediate complete revascularization group appeared to have a reduction in MI (1.9% vs. 4.5%) and fewer unplanned ischemia-driven revascularizations (4.2% vs. 6.7%).
The difference in MI was mainly driven by spontaneous MIs (not procedure related) that predominantly occurred in the time window between the index procedure and the planned date for the staged intervention, and an originally nonculprit lesion was identified as the cause for these events in almost all cases.
Subgroup analysis showed similar results across the patient population, including age, sex, and STEMI vs. non-STEMI presentation.
High rate of MI in staged group
Discussant of the study at the ACC session, Dipti Itchhaporia, MD, University of California, Irvine, said this was a “very important trial.”
She expressed surprise over the “remarkably high rate” of MI in the staged procedure group and asked Dr. Diletti why that might have occurred.
He responded that the operator may have misjudged the culprit lesion or that patients with ACS may have multiple unstable plaques and “treating the culprit lesion alone does not do the job.”
He added: “We need to look at the data more thoroughly to better understand this, but in both scenarios, immediate complete revascularization would prevent these events.”
Dr. Itchhaporia also pointed out a low rate of functional imaging used in the study.
Dr. Diletti replied that this reflected current European practice, but he acknowledged that, “in my opinion this reduces our ability to detect the culprit lesion.”
Commenting at an ACC press conference, David Moliterno, MD, Gill Heart and Vascular Institute, Lexington, Ky., said the trial poses the question “Can we fix it all at once?” and the results suggest “Yes, we can.”
He said this approach had the advantage of removing any uncertainly as to which was the culprit lesion. “We just fix everything – leave no blockage behind.”
But he pointed out that for some patients this may not be appropriate, such as those with compromised renal function, in whom excessive amounts of contrast material should be avoided.
CABG still needs to be considered
In a comment accompanying the Lancet publication, Tobias Pustjens, MD, Pieter Vriesendorp, MD, and Arnoud W.J. van’t Hof, MD, Cardiovascular Research Institute Maastricht (the Netherlands), note that more than half of the patients presenting with an ACS have multivessel coronary disease.
They say the trial results suggest that “pursuing an immediate complete revascularisation strategy, especially in times of reduced hospital capacity and staff scarcity, not only benefits the individual patient in clinical outcomes but can also safely reduce the pressure on health care systems.”
But they also point out that the possibility of coronary artery bypass grafting (CABG) should not be omitted, and that CABG is still the treatment of choice in patients with diabetes or complex coronary artery disease.
They conclude: “The results of the BIOVASC study move clinical practice forward from culprit-only to an immediate, complete revascularisation strategy. … However, further fine tuning of this treatment strategy to substantiate a role for intracoronary physiology assessment, intracoronary imaging, and guidance of the heart team decision is needed.”
The BIOVASC trial was supported by an unrestricted research grant from Biotronik AG. Dr. Diletti has received institutional research grants from Biotronik, Medtronic, ACIST Medical Systems, and Boston Scientific. Dr. van’t Hof has received institutional research grants from Biotronik.
A version of this article first appeared on Medscape.com.
Immediate complete revascularization during the index procedure might become the new treatment paradigm in patients with an acute coronary syndrome (ACS) and multivessel disease, based on results of the BIOVASC trial.
In the trial, in patients presenting with ACS and multivessel disease, immediate complete revascularization was noninferior to staged complete revascularization for the primary composite outcome and was associated with a reduction in myocardial infarction and unplanned ischemia-driven revascularization.
The BIOVASC trial was presented on March 5 by Roberto Diletti, MD, Erasmus University Medical Center, Rotterdam, the Netherlands, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The study was simultaneously published online in The Lancet.
“We did not detect an early safety signal against an immediate complete revascularization strategy,” the authors state in the Lancet paper, adding: “Treating physicians should not be concerned about potential risks associated with immediate treatment of nonculprit lesions.”
They note, “This strategy might be particularly effective in patients with only two-vessel disease and reasonably simple lesions, with a high likelihood of procedural success without excessive use of radiation, contrast dye, or other resources.”
The trial also showed a shorter hospital stay with an immediate complete revascularization strategy.
“Immediate complete revascularization might have potential health economic benefits because of the lower rate of myocardial infarction, including spontaneous myocardial infarction, and unplanned revascularizations, and the shorter overall hospital stay,” the researchers conclude.
Introducing his presentation, Dr. Diletti explained that multiple studies have established the clinical benefit of complete coronary revascularization as compared with exclusive reperfusion of the culprit lesion, but the optimal timing for nonculprit lesion revascularization remains unclear.
The BIOVASC trial, conducted in Belgium, Italy, the Netherlands, and Spain, involved 1,525 patients with ST-segment elevation MI (STEMI) or non-STEMI ACS and multivessel coronary artery disease with a clearly identifiable culprit lesion.
They were randomly assigned to undergo immediate complete revascularization (percutaneous coronary intervention [PCI] of the culprit lesion first, followed by other nonculprit lesions deemed to be clinically significant by the operator during the index procedure) or staged complete revascularization (PCI of only the culprit lesion during the index procedure and PCI of all nonculprit lesions deemed to be clinically significant within 6 weeks after the index procedure).
The primary outcome was the composite of all-cause mortality, MI, any unplanned ischemia-driven revascularization, or cerebrovascular events at 1 year after the index procedure.
The trial had a noninferiority design, with noninferiority of immediate to staged complete revascularization considered to be met if the upper boundary of the 95% confidence interval of the hazard ratio for the primary outcome did not exceed 1.39.
Among the trial population, 40% of patients had STEMI, 52% had non-STEMI, and 8% had unstable angina.
In the immediate complete revascularization group, 16 patients did not receive complete revascularization during the index procedure primarily because of prolonged procedure time, procedural complexity, or excessive contrast dye use.
In the staged group, 30% of patients underwent all subsequent procedures during the index hospitalization.
Results showed that the primary composite outcome at 1 year occurred in 7.6% of the immediate revascularization group and in 9.4% of the staged group, meeting the noninferiority criteria (HR, 0.78; 95% CI, 0.55-1.11; P for noninferiority = .0011).
Superiority of the immediate over the staged complete revascularization strategy was not met at 1-year follow-up (P for superiority = .17).
However, in the prespecified analysis of clinical events at 30 days after the index procedure, immediate complete revascularization was superior to staged revascularization in terms of the composite primary outcome (2.2% vs. 5.8%; HR, 0.38; P for superiority = .0007).
One-year results showed no difference in all-cause death between the two groups, but the immediate complete revascularization group appeared to have a reduction in MI (1.9% vs. 4.5%) and fewer unplanned ischemia-driven revascularizations (4.2% vs. 6.7%).
The difference in MI was mainly driven by spontaneous MIs (not procedure related) that predominantly occurred in the time window between the index procedure and the planned date for the staged intervention, and an originally nonculprit lesion was identified as the cause for these events in almost all cases.
Subgroup analysis showed similar results across the patient population, including age, sex, and STEMI vs. non-STEMI presentation.
High rate of MI in staged group
Discussant of the study at the ACC session, Dipti Itchhaporia, MD, University of California, Irvine, said this was a “very important trial.”
She expressed surprise over the “remarkably high rate” of MI in the staged procedure group and asked Dr. Diletti why that might have occurred.
He responded that the operator may have misjudged the culprit lesion or that patients with ACS may have multiple unstable plaques and “treating the culprit lesion alone does not do the job.”
He added: “We need to look at the data more thoroughly to better understand this, but in both scenarios, immediate complete revascularization would prevent these events.”
Dr. Itchhaporia also pointed out a low rate of functional imaging used in the study.
Dr. Diletti replied that this reflected current European practice, but he acknowledged that, “in my opinion this reduces our ability to detect the culprit lesion.”
Commenting at an ACC press conference, David Moliterno, MD, Gill Heart and Vascular Institute, Lexington, Ky., said the trial poses the question “Can we fix it all at once?” and the results suggest “Yes, we can.”
He said this approach had the advantage of removing any uncertainly as to which was the culprit lesion. “We just fix everything – leave no blockage behind.”
But he pointed out that for some patients this may not be appropriate, such as those with compromised renal function, in whom excessive amounts of contrast material should be avoided.
CABG still needs to be considered
In a comment accompanying the Lancet publication, Tobias Pustjens, MD, Pieter Vriesendorp, MD, and Arnoud W.J. van’t Hof, MD, Cardiovascular Research Institute Maastricht (the Netherlands), note that more than half of the patients presenting with an ACS have multivessel coronary disease.
They say the trial results suggest that “pursuing an immediate complete revascularisation strategy, especially in times of reduced hospital capacity and staff scarcity, not only benefits the individual patient in clinical outcomes but can also safely reduce the pressure on health care systems.”
But they also point out that the possibility of coronary artery bypass grafting (CABG) should not be omitted, and that CABG is still the treatment of choice in patients with diabetes or complex coronary artery disease.
They conclude: “The results of the BIOVASC study move clinical practice forward from culprit-only to an immediate, complete revascularisation strategy. … However, further fine tuning of this treatment strategy to substantiate a role for intracoronary physiology assessment, intracoronary imaging, and guidance of the heart team decision is needed.”
The BIOVASC trial was supported by an unrestricted research grant from Biotronik AG. Dr. Diletti has received institutional research grants from Biotronik, Medtronic, ACIST Medical Systems, and Boston Scientific. Dr. van’t Hof has received institutional research grants from Biotronik.
A version of this article first appeared on Medscape.com.
FROM ACS 2023
When intravascular imaging guides complex PCI, MACE risk is lowered
NEW ORLEANS – In patients undergoing percutaneous intervention (PCI) for complex coronary lesions, intravascular imaging is superior to angiography for reducing the risk of target lesion failure (TLF), according to results of a randomized trial.
Previous studies have produced the same conclusion, but the advantage was demonstrated this time in a multicenter well-powered randomized trial, principal investigator Joo Yong Hahn, MD, PhD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
The earlier studies “were not definitive,” said Dr. Hahn, pointing out that even those that were randomized lacked sufficient duration of follow-up or were not inclusive of a broad array of types of complex PCI.
In this clinical outcomes–driven study, called RENOVATE-COMPLEX-PCI, 1,639 patients undergoing complex PCI in 20 South Korean treatment centers were randomized in a 2:1 ratio to PCI guided by intravascular imaging or angiography alone. There were nine types of complex PCI eligible for trial entry, including bifurcated lesions, long lesions (expected stent length ≥ 38 mm), total coronary occlusions, lesions requiring multiple stents, severely calcified lesions, and lesions in multiple vessels.
Intravascular imaging in the experimental arm could be performed with either intravascular ultrasound (IVUS) or optical coherence tomography (OCT), according to Dr. Hahn. Because one might be better than the other for specific patient and lesions characteristics, the type of intravascular imaging in the experimental group was selected at the discretion of the treating investigator, reported Dr. Hahn, of the Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University, Seoul.
The primary TLF endpoint was defined as death from cardiovascular causes, target-vessel-related MI, and target-vessel revascularization.
Risk reduction of > 35% observed
After a median of 2.1 years of follow-up, the lower TLF incidence in the group with PCI guided by intravascular imaging (7.7% vs. 12.3%) translated into a 36% reduction in risk (hazard ratio, 0.64; P = .008).
Intravascular imaging was associated with a numerical reduction of each component of TLF. In the case of death from cardiovascular causes, the confidence interval remained below the line of unity (HR 0.47; 95% CI, 0.24-0.93).
Although this was not true for target vessel–related MI (HR, 0.74, 95% CI, 0.45-1.22) or target vessel revascularization (HR, 0.66; 95% CI, 0.36-1.22), it was also true of TLF without procedural-related MI (HR, 0.59; 95% CI, 0.39-0.90) and cardiac death or target vessel–related MI (HR, 0.63; 95% CI, 0.42-0.93).
With few exceptions, all of the secondary outcomes “moved in the right direction” to favor intravascular imaging, including death from any cause (HR 0.71, 95% CI, 0.44-1.15), reported Dr. Hahn, who noted that the results were simultaneously published in the New England Journal of Medicine.
When compared, there were no major baseline differences in the 1,092 patients with PCI guided by intravascular imaging relative to the 547 guided by angiography. The median age was 65.5 years. Most (79%) were male. About half (51%) had an acute coronary syndrome and the remainder had stable ischemic heart disease. The proportions of patients with hypertension (61%), dyslipidemia (51%), and diabetes (38%) were substantial. About 18% of patients were current smokers, 24% had a previous PCI, and 7% had a previous MI.
Stent types were similar in the two groups, and they were delivered by radial access. Procedural success was achieved in about 98% of both groups. Almost all patients were discharged on a statin, aspirin, and a P2Y12 inhibitor, and the other specific postprocedural medications were comparable in the two groups.
Advantage of intravascular imaging consistent
Of the complex lesions, most (55%) had diffuse long coronary artery lesions, but other types of complex PCI, including bifurcated lesions (22%), chronic total occlusions (20%), severely calcified lesions (14%), and ostial lesions of a major coronary artery (15%) were represented. Across these lesion types, intravascular imaging was favored over angiography for TLF at least numerically. The potential exceptions were lesions requiring at least three stents (HR, 1.24; 95% CI, 0.49-3.18), but confidence intervals were wide.
The trial was unblinded, but Dr. Hahn reported that imaging analyses were performed at a core laboratory and events were adjudicated by a committee with members unaware of trial group assignments.
One unanswered question is cost. Because intravascular imaging adds cost to PCI relative to angiography, cost-effectiveness analyses are needed to provide context for the decision to use this approach in all complex PCI patients. These analyses are planned.
Based on the consistency of these trial results with previous studies, almost all of which showed the same thing, “the intravascular imaging world has spoken,” said Wayne B. Batchelor, MD, director of interventional cardiology, Inova Heart and Vascular Institute, Fairfax, Va. “The only question now is when will the interventional community is going to listen.”
Dr. Batchelor predicted that these data will change the mindset of many practitioners “to shift the debate to why not do it [intravascular imaging] from why do it.”
“Only about 15% of PCI is performed with intravascular imaging in the United States, and these [results] argue that this number needs to go up,” Dr. Batchelor said. Although he said there are technical reasons, such as diffuse lesions or small vessels, that prevent intravascular imaging from being used in every complex patient, he suggested the data are compelling.
“If you apply this to the one million patients undergoing PCI in the United States, this will translate potentially into tens of thousands of patients protected from the TVF endpoint,” Dr. Batchelor said.
Dr. Hahn reports no potential conflicts of interest, but this investigator-initiated trial received funding from Boston Scientific and Abbott Vascular. Dr. Batchelor reports financial relationships with Abbott Vascular, Boston Scientific, Idorsia, Medtronic, and V-Wave Medical.
NEW ORLEANS – In patients undergoing percutaneous intervention (PCI) for complex coronary lesions, intravascular imaging is superior to angiography for reducing the risk of target lesion failure (TLF), according to results of a randomized trial.
Previous studies have produced the same conclusion, but the advantage was demonstrated this time in a multicenter well-powered randomized trial, principal investigator Joo Yong Hahn, MD, PhD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
The earlier studies “were not definitive,” said Dr. Hahn, pointing out that even those that were randomized lacked sufficient duration of follow-up or were not inclusive of a broad array of types of complex PCI.
In this clinical outcomes–driven study, called RENOVATE-COMPLEX-PCI, 1,639 patients undergoing complex PCI in 20 South Korean treatment centers were randomized in a 2:1 ratio to PCI guided by intravascular imaging or angiography alone. There were nine types of complex PCI eligible for trial entry, including bifurcated lesions, long lesions (expected stent length ≥ 38 mm), total coronary occlusions, lesions requiring multiple stents, severely calcified lesions, and lesions in multiple vessels.
Intravascular imaging in the experimental arm could be performed with either intravascular ultrasound (IVUS) or optical coherence tomography (OCT), according to Dr. Hahn. Because one might be better than the other for specific patient and lesions characteristics, the type of intravascular imaging in the experimental group was selected at the discretion of the treating investigator, reported Dr. Hahn, of the Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University, Seoul.
The primary TLF endpoint was defined as death from cardiovascular causes, target-vessel-related MI, and target-vessel revascularization.
Risk reduction of > 35% observed
After a median of 2.1 years of follow-up, the lower TLF incidence in the group with PCI guided by intravascular imaging (7.7% vs. 12.3%) translated into a 36% reduction in risk (hazard ratio, 0.64; P = .008).
Intravascular imaging was associated with a numerical reduction of each component of TLF. In the case of death from cardiovascular causes, the confidence interval remained below the line of unity (HR 0.47; 95% CI, 0.24-0.93).
Although this was not true for target vessel–related MI (HR, 0.74, 95% CI, 0.45-1.22) or target vessel revascularization (HR, 0.66; 95% CI, 0.36-1.22), it was also true of TLF without procedural-related MI (HR, 0.59; 95% CI, 0.39-0.90) and cardiac death or target vessel–related MI (HR, 0.63; 95% CI, 0.42-0.93).
With few exceptions, all of the secondary outcomes “moved in the right direction” to favor intravascular imaging, including death from any cause (HR 0.71, 95% CI, 0.44-1.15), reported Dr. Hahn, who noted that the results were simultaneously published in the New England Journal of Medicine.
When compared, there were no major baseline differences in the 1,092 patients with PCI guided by intravascular imaging relative to the 547 guided by angiography. The median age was 65.5 years. Most (79%) were male. About half (51%) had an acute coronary syndrome and the remainder had stable ischemic heart disease. The proportions of patients with hypertension (61%), dyslipidemia (51%), and diabetes (38%) were substantial. About 18% of patients were current smokers, 24% had a previous PCI, and 7% had a previous MI.
Stent types were similar in the two groups, and they were delivered by radial access. Procedural success was achieved in about 98% of both groups. Almost all patients were discharged on a statin, aspirin, and a P2Y12 inhibitor, and the other specific postprocedural medications were comparable in the two groups.
Advantage of intravascular imaging consistent
Of the complex lesions, most (55%) had diffuse long coronary artery lesions, but other types of complex PCI, including bifurcated lesions (22%), chronic total occlusions (20%), severely calcified lesions (14%), and ostial lesions of a major coronary artery (15%) were represented. Across these lesion types, intravascular imaging was favored over angiography for TLF at least numerically. The potential exceptions were lesions requiring at least three stents (HR, 1.24; 95% CI, 0.49-3.18), but confidence intervals were wide.
The trial was unblinded, but Dr. Hahn reported that imaging analyses were performed at a core laboratory and events were adjudicated by a committee with members unaware of trial group assignments.
One unanswered question is cost. Because intravascular imaging adds cost to PCI relative to angiography, cost-effectiveness analyses are needed to provide context for the decision to use this approach in all complex PCI patients. These analyses are planned.
Based on the consistency of these trial results with previous studies, almost all of which showed the same thing, “the intravascular imaging world has spoken,” said Wayne B. Batchelor, MD, director of interventional cardiology, Inova Heart and Vascular Institute, Fairfax, Va. “The only question now is when will the interventional community is going to listen.”
Dr. Batchelor predicted that these data will change the mindset of many practitioners “to shift the debate to why not do it [intravascular imaging] from why do it.”
“Only about 15% of PCI is performed with intravascular imaging in the United States, and these [results] argue that this number needs to go up,” Dr. Batchelor said. Although he said there are technical reasons, such as diffuse lesions or small vessels, that prevent intravascular imaging from being used in every complex patient, he suggested the data are compelling.
“If you apply this to the one million patients undergoing PCI in the United States, this will translate potentially into tens of thousands of patients protected from the TVF endpoint,” Dr. Batchelor said.
Dr. Hahn reports no potential conflicts of interest, but this investigator-initiated trial received funding from Boston Scientific and Abbott Vascular. Dr. Batchelor reports financial relationships with Abbott Vascular, Boston Scientific, Idorsia, Medtronic, and V-Wave Medical.
NEW ORLEANS – In patients undergoing percutaneous intervention (PCI) for complex coronary lesions, intravascular imaging is superior to angiography for reducing the risk of target lesion failure (TLF), according to results of a randomized trial.
Previous studies have produced the same conclusion, but the advantage was demonstrated this time in a multicenter well-powered randomized trial, principal investigator Joo Yong Hahn, MD, PhD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
The earlier studies “were not definitive,” said Dr. Hahn, pointing out that even those that were randomized lacked sufficient duration of follow-up or were not inclusive of a broad array of types of complex PCI.
In this clinical outcomes–driven study, called RENOVATE-COMPLEX-PCI, 1,639 patients undergoing complex PCI in 20 South Korean treatment centers were randomized in a 2:1 ratio to PCI guided by intravascular imaging or angiography alone. There were nine types of complex PCI eligible for trial entry, including bifurcated lesions, long lesions (expected stent length ≥ 38 mm), total coronary occlusions, lesions requiring multiple stents, severely calcified lesions, and lesions in multiple vessels.
Intravascular imaging in the experimental arm could be performed with either intravascular ultrasound (IVUS) or optical coherence tomography (OCT), according to Dr. Hahn. Because one might be better than the other for specific patient and lesions characteristics, the type of intravascular imaging in the experimental group was selected at the discretion of the treating investigator, reported Dr. Hahn, of the Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University, Seoul.
The primary TLF endpoint was defined as death from cardiovascular causes, target-vessel-related MI, and target-vessel revascularization.
Risk reduction of > 35% observed
After a median of 2.1 years of follow-up, the lower TLF incidence in the group with PCI guided by intravascular imaging (7.7% vs. 12.3%) translated into a 36% reduction in risk (hazard ratio, 0.64; P = .008).
Intravascular imaging was associated with a numerical reduction of each component of TLF. In the case of death from cardiovascular causes, the confidence interval remained below the line of unity (HR 0.47; 95% CI, 0.24-0.93).
Although this was not true for target vessel–related MI (HR, 0.74, 95% CI, 0.45-1.22) or target vessel revascularization (HR, 0.66; 95% CI, 0.36-1.22), it was also true of TLF without procedural-related MI (HR, 0.59; 95% CI, 0.39-0.90) and cardiac death or target vessel–related MI (HR, 0.63; 95% CI, 0.42-0.93).
With few exceptions, all of the secondary outcomes “moved in the right direction” to favor intravascular imaging, including death from any cause (HR 0.71, 95% CI, 0.44-1.15), reported Dr. Hahn, who noted that the results were simultaneously published in the New England Journal of Medicine.
When compared, there were no major baseline differences in the 1,092 patients with PCI guided by intravascular imaging relative to the 547 guided by angiography. The median age was 65.5 years. Most (79%) were male. About half (51%) had an acute coronary syndrome and the remainder had stable ischemic heart disease. The proportions of patients with hypertension (61%), dyslipidemia (51%), and diabetes (38%) were substantial. About 18% of patients were current smokers, 24% had a previous PCI, and 7% had a previous MI.
Stent types were similar in the two groups, and they were delivered by radial access. Procedural success was achieved in about 98% of both groups. Almost all patients were discharged on a statin, aspirin, and a P2Y12 inhibitor, and the other specific postprocedural medications were comparable in the two groups.
Advantage of intravascular imaging consistent
Of the complex lesions, most (55%) had diffuse long coronary artery lesions, but other types of complex PCI, including bifurcated lesions (22%), chronic total occlusions (20%), severely calcified lesions (14%), and ostial lesions of a major coronary artery (15%) were represented. Across these lesion types, intravascular imaging was favored over angiography for TLF at least numerically. The potential exceptions were lesions requiring at least three stents (HR, 1.24; 95% CI, 0.49-3.18), but confidence intervals were wide.
The trial was unblinded, but Dr. Hahn reported that imaging analyses were performed at a core laboratory and events were adjudicated by a committee with members unaware of trial group assignments.
One unanswered question is cost. Because intravascular imaging adds cost to PCI relative to angiography, cost-effectiveness analyses are needed to provide context for the decision to use this approach in all complex PCI patients. These analyses are planned.
Based on the consistency of these trial results with previous studies, almost all of which showed the same thing, “the intravascular imaging world has spoken,” said Wayne B. Batchelor, MD, director of interventional cardiology, Inova Heart and Vascular Institute, Fairfax, Va. “The only question now is when will the interventional community is going to listen.”
Dr. Batchelor predicted that these data will change the mindset of many practitioners “to shift the debate to why not do it [intravascular imaging] from why do it.”
“Only about 15% of PCI is performed with intravascular imaging in the United States, and these [results] argue that this number needs to go up,” Dr. Batchelor said. Although he said there are technical reasons, such as diffuse lesions or small vessels, that prevent intravascular imaging from being used in every complex patient, he suggested the data are compelling.
“If you apply this to the one million patients undergoing PCI in the United States, this will translate potentially into tens of thousands of patients protected from the TVF endpoint,” Dr. Batchelor said.
Dr. Hahn reports no potential conflicts of interest, but this investigator-initiated trial received funding from Boston Scientific and Abbott Vascular. Dr. Batchelor reports financial relationships with Abbott Vascular, Boston Scientific, Idorsia, Medtronic, and V-Wave Medical.
AT ACC 2023
Viability-guided PCI doubted in stable severe CAD: REVIVED-BCIS2
There is no magical amount of viable ventricular myocardium that makes percutaneous coronary intervention (PCI) an effective addition to optimal medical therapy (OMT) in stable patients with coronary disease and poor ventricular function, suggests an analysis from a major trial.
The REVIVED-BCIS2 trial recently made waves when it showed no clinical advantage from adding PCI to OMT in stable patients with severe ischemic left ventricular (LV) dysfunction. All the patients had shown viable but dysfunctional myocardium that could potentially be revascularized.
But in a secondary analysis, extent of such hibernating heart muscle was not a good predictor of clinical outcomes, which in the trial meant death from any cause or hospitalization for heart failure (HHF).
Burden of myocardial scar tissue, however, turned out to be a potent predictor of clinical risk regardless of coronary disease severity or even LV ejection fraction (LVEF).
Because myocardial viability tracks poorly with outcomes in patients like those enrolled in the trial, as the new analysis suggests, conventional viability testing isn’t an effective guide for deciding who among them should get PCI, Divaka Perera, MD, said in an interview.
Dr. Perera, of King’s College London and the trial’s principal investigator, presented the REVIVED-BCIS2 secondary results at the joint scientific sessions of the American College of Cardiology and the World Heart Federation..
Viability testing for ischemia, he noted, is often used in practice to aid revascularization decisions. As the extent of myocardial viability can vary, it’s been asked – ever since the trial’s primary publication – whether there could be “a sweet spot or Goldilocks zone of viability that would allow prediction of which patients will do better with PCI compared to medical therapy,” Dr. Perera said. “The trial conclusively shows that is not the case.”
That the extent of hibernating myocardium, which is viable but dysfunctional, didn’t predict clinical outcomes or LV functional recovery “is disruptive of current practice and challenges a view that’s been held for decades.”
The trial’s 700 patients receiving OMT had been randomly assigned to undergo PCI or not, 347 and 353 patients, respectively. About 12% of the total were women.
About 70% of patients underwent baseline and follow-up myocardial viability testing using cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement for estimation of scar burden; the remainder underwent dobutamine-stress echocardiography. All imaging assessments were conducted at independent core laboratories, Dr. Perera reported.
Extent of myocardial viability was defined three ways: volume of hibernating heart muscle, total volume of viable myocardium, and scar burden – all expressed as a percentage of total LV volume.
Every 10% increment in LV volume found to be hibernating related to a hazard ratio of 0.98 (95% confidence interval, 0.93-1.04; P = .56) for all-cause mortality or HHF at a median of 3.3 years. The analysis was adjusted for age, sex, diabetes, previous HHF, chronic renal failure, extent of CAD, type of viability testing, and baseline LVEF.
The adjusted HR for the same percentage increment in total viable myocardium was marginally significantly reduced at 0.93 (95% CI, 0.87-1.00; P = .048).
The correlation with scar burden was stronger. The adjusted composite-endpoint HR per 10% increment in scar burden was significantly increased at 1.18 (95% CI, 1.04-1.33; P = .009).
Extent of myocardial viability by tertiles, regardless of viability definition, did not highlight any group with a reduced risk for death or HHF, or group with better LV functional recovery, from OMT plus PCI, compared with OMT alone.
The findings appear to suggest that scar burden, but not extent of viability as it’s usually measured, may effectively guide PCI decisions in such patients, Dr. Perera said.
“I would say that viability testing as we understand it now, based on the paradigm of hibernating myocardium, is very useful,” he said, “but that is not the only information we can get from a viability test.”
Scar burden can also be determined from the same tests but isn’t typically looked at. “We’re actually collecting this information but not using it,” Dr. Perera said. “When we do, it is really powerfully predictive” of both clinical outcomes and LV functional recovery. “Yet scar burden is not in any of the guidelines for stratifying risk.”
REVIVED-BCIS2 was funded by the National Institute for Health and Care Research Health Technology Assessment Program. Dr. Perera had no disclosures.
A version of this article first appeared on Medscape.com.
There is no magical amount of viable ventricular myocardium that makes percutaneous coronary intervention (PCI) an effective addition to optimal medical therapy (OMT) in stable patients with coronary disease and poor ventricular function, suggests an analysis from a major trial.
The REVIVED-BCIS2 trial recently made waves when it showed no clinical advantage from adding PCI to OMT in stable patients with severe ischemic left ventricular (LV) dysfunction. All the patients had shown viable but dysfunctional myocardium that could potentially be revascularized.
But in a secondary analysis, extent of such hibernating heart muscle was not a good predictor of clinical outcomes, which in the trial meant death from any cause or hospitalization for heart failure (HHF).
Burden of myocardial scar tissue, however, turned out to be a potent predictor of clinical risk regardless of coronary disease severity or even LV ejection fraction (LVEF).
Because myocardial viability tracks poorly with outcomes in patients like those enrolled in the trial, as the new analysis suggests, conventional viability testing isn’t an effective guide for deciding who among them should get PCI, Divaka Perera, MD, said in an interview.
Dr. Perera, of King’s College London and the trial’s principal investigator, presented the REVIVED-BCIS2 secondary results at the joint scientific sessions of the American College of Cardiology and the World Heart Federation..
Viability testing for ischemia, he noted, is often used in practice to aid revascularization decisions. As the extent of myocardial viability can vary, it’s been asked – ever since the trial’s primary publication – whether there could be “a sweet spot or Goldilocks zone of viability that would allow prediction of which patients will do better with PCI compared to medical therapy,” Dr. Perera said. “The trial conclusively shows that is not the case.”
That the extent of hibernating myocardium, which is viable but dysfunctional, didn’t predict clinical outcomes or LV functional recovery “is disruptive of current practice and challenges a view that’s been held for decades.”
The trial’s 700 patients receiving OMT had been randomly assigned to undergo PCI or not, 347 and 353 patients, respectively. About 12% of the total were women.
About 70% of patients underwent baseline and follow-up myocardial viability testing using cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement for estimation of scar burden; the remainder underwent dobutamine-stress echocardiography. All imaging assessments were conducted at independent core laboratories, Dr. Perera reported.
Extent of myocardial viability was defined three ways: volume of hibernating heart muscle, total volume of viable myocardium, and scar burden – all expressed as a percentage of total LV volume.
Every 10% increment in LV volume found to be hibernating related to a hazard ratio of 0.98 (95% confidence interval, 0.93-1.04; P = .56) for all-cause mortality or HHF at a median of 3.3 years. The analysis was adjusted for age, sex, diabetes, previous HHF, chronic renal failure, extent of CAD, type of viability testing, and baseline LVEF.
The adjusted HR for the same percentage increment in total viable myocardium was marginally significantly reduced at 0.93 (95% CI, 0.87-1.00; P = .048).
The correlation with scar burden was stronger. The adjusted composite-endpoint HR per 10% increment in scar burden was significantly increased at 1.18 (95% CI, 1.04-1.33; P = .009).
Extent of myocardial viability by tertiles, regardless of viability definition, did not highlight any group with a reduced risk for death or HHF, or group with better LV functional recovery, from OMT plus PCI, compared with OMT alone.
The findings appear to suggest that scar burden, but not extent of viability as it’s usually measured, may effectively guide PCI decisions in such patients, Dr. Perera said.
“I would say that viability testing as we understand it now, based on the paradigm of hibernating myocardium, is very useful,” he said, “but that is not the only information we can get from a viability test.”
Scar burden can also be determined from the same tests but isn’t typically looked at. “We’re actually collecting this information but not using it,” Dr. Perera said. “When we do, it is really powerfully predictive” of both clinical outcomes and LV functional recovery. “Yet scar burden is not in any of the guidelines for stratifying risk.”
REVIVED-BCIS2 was funded by the National Institute for Health and Care Research Health Technology Assessment Program. Dr. Perera had no disclosures.
A version of this article first appeared on Medscape.com.
There is no magical amount of viable ventricular myocardium that makes percutaneous coronary intervention (PCI) an effective addition to optimal medical therapy (OMT) in stable patients with coronary disease and poor ventricular function, suggests an analysis from a major trial.
The REVIVED-BCIS2 trial recently made waves when it showed no clinical advantage from adding PCI to OMT in stable patients with severe ischemic left ventricular (LV) dysfunction. All the patients had shown viable but dysfunctional myocardium that could potentially be revascularized.
But in a secondary analysis, extent of such hibernating heart muscle was not a good predictor of clinical outcomes, which in the trial meant death from any cause or hospitalization for heart failure (HHF).
Burden of myocardial scar tissue, however, turned out to be a potent predictor of clinical risk regardless of coronary disease severity or even LV ejection fraction (LVEF).
Because myocardial viability tracks poorly with outcomes in patients like those enrolled in the trial, as the new analysis suggests, conventional viability testing isn’t an effective guide for deciding who among them should get PCI, Divaka Perera, MD, said in an interview.
Dr. Perera, of King’s College London and the trial’s principal investigator, presented the REVIVED-BCIS2 secondary results at the joint scientific sessions of the American College of Cardiology and the World Heart Federation..
Viability testing for ischemia, he noted, is often used in practice to aid revascularization decisions. As the extent of myocardial viability can vary, it’s been asked – ever since the trial’s primary publication – whether there could be “a sweet spot or Goldilocks zone of viability that would allow prediction of which patients will do better with PCI compared to medical therapy,” Dr. Perera said. “The trial conclusively shows that is not the case.”
That the extent of hibernating myocardium, which is viable but dysfunctional, didn’t predict clinical outcomes or LV functional recovery “is disruptive of current practice and challenges a view that’s been held for decades.”
The trial’s 700 patients receiving OMT had been randomly assigned to undergo PCI or not, 347 and 353 patients, respectively. About 12% of the total were women.
About 70% of patients underwent baseline and follow-up myocardial viability testing using cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement for estimation of scar burden; the remainder underwent dobutamine-stress echocardiography. All imaging assessments were conducted at independent core laboratories, Dr. Perera reported.
Extent of myocardial viability was defined three ways: volume of hibernating heart muscle, total volume of viable myocardium, and scar burden – all expressed as a percentage of total LV volume.
Every 10% increment in LV volume found to be hibernating related to a hazard ratio of 0.98 (95% confidence interval, 0.93-1.04; P = .56) for all-cause mortality or HHF at a median of 3.3 years. The analysis was adjusted for age, sex, diabetes, previous HHF, chronic renal failure, extent of CAD, type of viability testing, and baseline LVEF.
The adjusted HR for the same percentage increment in total viable myocardium was marginally significantly reduced at 0.93 (95% CI, 0.87-1.00; P = .048).
The correlation with scar burden was stronger. The adjusted composite-endpoint HR per 10% increment in scar burden was significantly increased at 1.18 (95% CI, 1.04-1.33; P = .009).
Extent of myocardial viability by tertiles, regardless of viability definition, did not highlight any group with a reduced risk for death or HHF, or group with better LV functional recovery, from OMT plus PCI, compared with OMT alone.
The findings appear to suggest that scar burden, but not extent of viability as it’s usually measured, may effectively guide PCI decisions in such patients, Dr. Perera said.
“I would say that viability testing as we understand it now, based on the paradigm of hibernating myocardium, is very useful,” he said, “but that is not the only information we can get from a viability test.”
Scar burden can also be determined from the same tests but isn’t typically looked at. “We’re actually collecting this information but not using it,” Dr. Perera said. “When we do, it is really powerfully predictive” of both clinical outcomes and LV functional recovery. “Yet scar burden is not in any of the guidelines for stratifying risk.”
REVIVED-BCIS2 was funded by the National Institute for Health and Care Research Health Technology Assessment Program. Dr. Perera had no disclosures.
A version of this article first appeared on Medscape.com.
FROM ACC 2023
Atorvastatin cut anthracycline cardiac dysfunction in lymphoma
NEW ORLEANS – Atorvastatin treatment of patients with lymphoma undergoing treatment with an anthracycline significantly cut the incidence of incident cardiac dysfunction by about two-thirds during 12 months of treatment, in a multicenter, randomized trial with 300 enrolled patients.
“These data support the use of atorvastatin among patients with lymphoma being treated with anthracyclines where prevention of cardiac systolic dysfunction is important,” concluded Tomas G. Neilan, MD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
He highlighted that an important difference between the new study, STOP-CA, and a major prior study with a neutral effect published in 2022, was that STOP-CA “was powered for a major change” in cardiac function as the study’s primary outcome, a decline from baseline in left ventricular ejection fraction (LVEF) of at least 10% that also reduced ejection fraction to less than 55%.
“We can consider these medications [atorvastatin] for patients at higher risk for cardiac toxicity from anthracyclines, such as patients who receive a higher dose of an anthracycline, older patients, people with obesity, and women, commented Anita Deswal, MD, professor and chair of the department of cardiology at the University of Texas MD Anderson Cancer Center, Houston, who was not involved with the study.
A basis for an ‘important discussion’ with patients
“For patients receiving higher doses of anthracyclines, the STOP-CA trial says that whether to start a statin for cardiac protection is now an important discussion” for these patients to have with their treating clinicians. ”That was not the case before today,” commented Ronald M. Witteles, MD, a cardiologist and professor who specializes in cardio-oncology at Stanford (Calif.) University.
“For a patient being treated for lymphoma or for another cancer and treated with equal or higher anthracycline doses, such as patients with a sarcoma, this trial’s results at the very least warrant a discussion between physicians and patients to make the decision,” Dr. Witteles, who was not involved in the study, said in an interview. But he also cautioned that “whether an individual patient should take a statin in this scenario is still not a no-brainer. While the trial was positive, it was for an imaging rather than for a clinical endpoint.”
Experts noted that a similar study with the clinical endpoint of heart failure would require both many more randomized patients as well as much longer follow-up. STOP-CA was not powered for this endpoint. During its 12-month duration, a total of 11 patients developed heart failure, with no between group difference.
STOP-CA enrolled adults with lymphoma (Hodgkin or non-Hodgkin) and scheduled to undergo anthracycline treatment at eight U.S. centers and one in Canada, and excluded patients already on statin treatment or those for whom a statin was already indicated. Of the 300 enrolled patients, 286 had 12-month follow-up. Randomization assigned patients to receive either 40 mg daily of atorvastatin or placebo.
Their cumulative, median anthracycline dose was 300 mg/m2, which is typical for treating lymphoma, but higher than the typical dose use for patients with breast cancer. At baseline, average LVEF was 63%, and after 12 months this had declined to 59%. Forty-six of the 286 patients assessed after 12 months fulfilled the primary outcome of at least a 10–percentage point reduction from baseline in their LVEF and a decline in LVEF to less than 55%. Researchers used cardiac MR to assess LVEF at baseline, and in most patients at follow-up, but a minority of patients had their follow-up assessments by echocardiography because of logistical issues. Greater than 90% of patients were adherent to their assigned regimen.
Tripled incidence of cardiac dysfunction in placebo patients
The incidence of this outcome was 9% among the patients who received atorvastatin, and 22% among those on placebo, a significant difference. The calculated odds of the primary outcome was 2.9-fold more likely among the patients treated with placebo, compared with those who received atorvastatin, also a significant difference.
The study’s secondary outcome was patients who had at least a 5% drop from baseline in their LVEF and with a LVEF of less than 55% after 12 months. This outcome occurred in 13% of patients treated with atorvastatin and in 29% of those who received placebo, a significant difference.
The atorvastatin and placebo arms showed no significant differences in adverse events during the study, with roughly similar incidence rates for muscle pain, elevated liver enzymes, and renal failure. None of the enrolled patients developed myositis.
Atorvastatin treatment also produced an expected average 37% decline from baseline in levels of LDL cholesterol.
“This was a well-designed and important trial,” said Dr. Witteles. “Anthracyclines remain a mainstay of cancer therapies for a number of malignancies, such as lymphoma and sarcoma, and the cardiac side effects of development of cardiac dysfunction are unequivocally real.”
The importance of a clinically meaningful effect
The results especially contrast with the findings from the PREVENT study, published in 2022, which compared a daily, 40-mg atorvastatin treatment with placebo in 279 randomized patients with breast cancer and treated for 24 months. However, patients in PREVENT had a cumulative, median anthracycline dose of 240 mg/m2, and the study’s primary outcome was the average change from baseline in LVEF after 24 months of treatment, which was a reduction of 0.08 percentage points in the placebo arm, a nonsignificant difference.
In STOP-CA, the average change in LVEF from baseline was a 1–percentage point reduction in the placebo arm, compared with the atorvastatin-treated patients, a difference that was statistically significant, but “not clinically significant,” said Dr. Neilan, director of the cardio-oncology program at Massachusetts General Hospital, Boston. He cited the good fortune of the STOP-CA investigators when they received a recommendation from reviewers early on to design their study to track a clinically meaningful change in LVEF rather than just looking at the average overall change.
Dr. Deswal also noted that it is unlikely that future studies will examine the efficacy of a statin for preventing LVEF in patients across the range of cancers that are eligible for anthracycline treatment. As a result, she predicted that “we may have to extrapolate” the results from STOP-CA to patients with other cancer types.
STOP-CA received no commercial funding. Dr. Neilan has been a consultant for and received fees from Abbvie, Amgen, Bristol-Myers Squibb, CRC Oncology, Genentech, Roche, and Sanofi, and has received grant funding from AstraZeneca and Bristol Myers Squib. Dr. Deswal and Dr. Witteles had no relevant disclosures.
NEW ORLEANS – Atorvastatin treatment of patients with lymphoma undergoing treatment with an anthracycline significantly cut the incidence of incident cardiac dysfunction by about two-thirds during 12 months of treatment, in a multicenter, randomized trial with 300 enrolled patients.
“These data support the use of atorvastatin among patients with lymphoma being treated with anthracyclines where prevention of cardiac systolic dysfunction is important,” concluded Tomas G. Neilan, MD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
He highlighted that an important difference between the new study, STOP-CA, and a major prior study with a neutral effect published in 2022, was that STOP-CA “was powered for a major change” in cardiac function as the study’s primary outcome, a decline from baseline in left ventricular ejection fraction (LVEF) of at least 10% that also reduced ejection fraction to less than 55%.
“We can consider these medications [atorvastatin] for patients at higher risk for cardiac toxicity from anthracyclines, such as patients who receive a higher dose of an anthracycline, older patients, people with obesity, and women, commented Anita Deswal, MD, professor and chair of the department of cardiology at the University of Texas MD Anderson Cancer Center, Houston, who was not involved with the study.
A basis for an ‘important discussion’ with patients
“For patients receiving higher doses of anthracyclines, the STOP-CA trial says that whether to start a statin for cardiac protection is now an important discussion” for these patients to have with their treating clinicians. ”That was not the case before today,” commented Ronald M. Witteles, MD, a cardiologist and professor who specializes in cardio-oncology at Stanford (Calif.) University.
“For a patient being treated for lymphoma or for another cancer and treated with equal or higher anthracycline doses, such as patients with a sarcoma, this trial’s results at the very least warrant a discussion between physicians and patients to make the decision,” Dr. Witteles, who was not involved in the study, said in an interview. But he also cautioned that “whether an individual patient should take a statin in this scenario is still not a no-brainer. While the trial was positive, it was for an imaging rather than for a clinical endpoint.”
Experts noted that a similar study with the clinical endpoint of heart failure would require both many more randomized patients as well as much longer follow-up. STOP-CA was not powered for this endpoint. During its 12-month duration, a total of 11 patients developed heart failure, with no between group difference.
STOP-CA enrolled adults with lymphoma (Hodgkin or non-Hodgkin) and scheduled to undergo anthracycline treatment at eight U.S. centers and one in Canada, and excluded patients already on statin treatment or those for whom a statin was already indicated. Of the 300 enrolled patients, 286 had 12-month follow-up. Randomization assigned patients to receive either 40 mg daily of atorvastatin or placebo.
Their cumulative, median anthracycline dose was 300 mg/m2, which is typical for treating lymphoma, but higher than the typical dose use for patients with breast cancer. At baseline, average LVEF was 63%, and after 12 months this had declined to 59%. Forty-six of the 286 patients assessed after 12 months fulfilled the primary outcome of at least a 10–percentage point reduction from baseline in their LVEF and a decline in LVEF to less than 55%. Researchers used cardiac MR to assess LVEF at baseline, and in most patients at follow-up, but a minority of patients had their follow-up assessments by echocardiography because of logistical issues. Greater than 90% of patients were adherent to their assigned regimen.
Tripled incidence of cardiac dysfunction in placebo patients
The incidence of this outcome was 9% among the patients who received atorvastatin, and 22% among those on placebo, a significant difference. The calculated odds of the primary outcome was 2.9-fold more likely among the patients treated with placebo, compared with those who received atorvastatin, also a significant difference.
The study’s secondary outcome was patients who had at least a 5% drop from baseline in their LVEF and with a LVEF of less than 55% after 12 months. This outcome occurred in 13% of patients treated with atorvastatin and in 29% of those who received placebo, a significant difference.
The atorvastatin and placebo arms showed no significant differences in adverse events during the study, with roughly similar incidence rates for muscle pain, elevated liver enzymes, and renal failure. None of the enrolled patients developed myositis.
Atorvastatin treatment also produced an expected average 37% decline from baseline in levels of LDL cholesterol.
“This was a well-designed and important trial,” said Dr. Witteles. “Anthracyclines remain a mainstay of cancer therapies for a number of malignancies, such as lymphoma and sarcoma, and the cardiac side effects of development of cardiac dysfunction are unequivocally real.”
The importance of a clinically meaningful effect
The results especially contrast with the findings from the PREVENT study, published in 2022, which compared a daily, 40-mg atorvastatin treatment with placebo in 279 randomized patients with breast cancer and treated for 24 months. However, patients in PREVENT had a cumulative, median anthracycline dose of 240 mg/m2, and the study’s primary outcome was the average change from baseline in LVEF after 24 months of treatment, which was a reduction of 0.08 percentage points in the placebo arm, a nonsignificant difference.
In STOP-CA, the average change in LVEF from baseline was a 1–percentage point reduction in the placebo arm, compared with the atorvastatin-treated patients, a difference that was statistically significant, but “not clinically significant,” said Dr. Neilan, director of the cardio-oncology program at Massachusetts General Hospital, Boston. He cited the good fortune of the STOP-CA investigators when they received a recommendation from reviewers early on to design their study to track a clinically meaningful change in LVEF rather than just looking at the average overall change.
Dr. Deswal also noted that it is unlikely that future studies will examine the efficacy of a statin for preventing LVEF in patients across the range of cancers that are eligible for anthracycline treatment. As a result, she predicted that “we may have to extrapolate” the results from STOP-CA to patients with other cancer types.
STOP-CA received no commercial funding. Dr. Neilan has been a consultant for and received fees from Abbvie, Amgen, Bristol-Myers Squibb, CRC Oncology, Genentech, Roche, and Sanofi, and has received grant funding from AstraZeneca and Bristol Myers Squib. Dr. Deswal and Dr. Witteles had no relevant disclosures.
NEW ORLEANS – Atorvastatin treatment of patients with lymphoma undergoing treatment with an anthracycline significantly cut the incidence of incident cardiac dysfunction by about two-thirds during 12 months of treatment, in a multicenter, randomized trial with 300 enrolled patients.
“These data support the use of atorvastatin among patients with lymphoma being treated with anthracyclines where prevention of cardiac systolic dysfunction is important,” concluded Tomas G. Neilan, MD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
He highlighted that an important difference between the new study, STOP-CA, and a major prior study with a neutral effect published in 2022, was that STOP-CA “was powered for a major change” in cardiac function as the study’s primary outcome, a decline from baseline in left ventricular ejection fraction (LVEF) of at least 10% that also reduced ejection fraction to less than 55%.
“We can consider these medications [atorvastatin] for patients at higher risk for cardiac toxicity from anthracyclines, such as patients who receive a higher dose of an anthracycline, older patients, people with obesity, and women, commented Anita Deswal, MD, professor and chair of the department of cardiology at the University of Texas MD Anderson Cancer Center, Houston, who was not involved with the study.
A basis for an ‘important discussion’ with patients
“For patients receiving higher doses of anthracyclines, the STOP-CA trial says that whether to start a statin for cardiac protection is now an important discussion” for these patients to have with their treating clinicians. ”That was not the case before today,” commented Ronald M. Witteles, MD, a cardiologist and professor who specializes in cardio-oncology at Stanford (Calif.) University.
“For a patient being treated for lymphoma or for another cancer and treated with equal or higher anthracycline doses, such as patients with a sarcoma, this trial’s results at the very least warrant a discussion between physicians and patients to make the decision,” Dr. Witteles, who was not involved in the study, said in an interview. But he also cautioned that “whether an individual patient should take a statin in this scenario is still not a no-brainer. While the trial was positive, it was for an imaging rather than for a clinical endpoint.”
Experts noted that a similar study with the clinical endpoint of heart failure would require both many more randomized patients as well as much longer follow-up. STOP-CA was not powered for this endpoint. During its 12-month duration, a total of 11 patients developed heart failure, with no between group difference.
STOP-CA enrolled adults with lymphoma (Hodgkin or non-Hodgkin) and scheduled to undergo anthracycline treatment at eight U.S. centers and one in Canada, and excluded patients already on statin treatment or those for whom a statin was already indicated. Of the 300 enrolled patients, 286 had 12-month follow-up. Randomization assigned patients to receive either 40 mg daily of atorvastatin or placebo.
Their cumulative, median anthracycline dose was 300 mg/m2, which is typical for treating lymphoma, but higher than the typical dose use for patients with breast cancer. At baseline, average LVEF was 63%, and after 12 months this had declined to 59%. Forty-six of the 286 patients assessed after 12 months fulfilled the primary outcome of at least a 10–percentage point reduction from baseline in their LVEF and a decline in LVEF to less than 55%. Researchers used cardiac MR to assess LVEF at baseline, and in most patients at follow-up, but a minority of patients had their follow-up assessments by echocardiography because of logistical issues. Greater than 90% of patients were adherent to their assigned regimen.
Tripled incidence of cardiac dysfunction in placebo patients
The incidence of this outcome was 9% among the patients who received atorvastatin, and 22% among those on placebo, a significant difference. The calculated odds of the primary outcome was 2.9-fold more likely among the patients treated with placebo, compared with those who received atorvastatin, also a significant difference.
The study’s secondary outcome was patients who had at least a 5% drop from baseline in their LVEF and with a LVEF of less than 55% after 12 months. This outcome occurred in 13% of patients treated with atorvastatin and in 29% of those who received placebo, a significant difference.
The atorvastatin and placebo arms showed no significant differences in adverse events during the study, with roughly similar incidence rates for muscle pain, elevated liver enzymes, and renal failure. None of the enrolled patients developed myositis.
Atorvastatin treatment also produced an expected average 37% decline from baseline in levels of LDL cholesterol.
“This was a well-designed and important trial,” said Dr. Witteles. “Anthracyclines remain a mainstay of cancer therapies for a number of malignancies, such as lymphoma and sarcoma, and the cardiac side effects of development of cardiac dysfunction are unequivocally real.”
The importance of a clinically meaningful effect
The results especially contrast with the findings from the PREVENT study, published in 2022, which compared a daily, 40-mg atorvastatin treatment with placebo in 279 randomized patients with breast cancer and treated for 24 months. However, patients in PREVENT had a cumulative, median anthracycline dose of 240 mg/m2, and the study’s primary outcome was the average change from baseline in LVEF after 24 months of treatment, which was a reduction of 0.08 percentage points in the placebo arm, a nonsignificant difference.
In STOP-CA, the average change in LVEF from baseline was a 1–percentage point reduction in the placebo arm, compared with the atorvastatin-treated patients, a difference that was statistically significant, but “not clinically significant,” said Dr. Neilan, director of the cardio-oncology program at Massachusetts General Hospital, Boston. He cited the good fortune of the STOP-CA investigators when they received a recommendation from reviewers early on to design their study to track a clinically meaningful change in LVEF rather than just looking at the average overall change.
Dr. Deswal also noted that it is unlikely that future studies will examine the efficacy of a statin for preventing LVEF in patients across the range of cancers that are eligible for anthracycline treatment. As a result, she predicted that “we may have to extrapolate” the results from STOP-CA to patients with other cancer types.
STOP-CA received no commercial funding. Dr. Neilan has been a consultant for and received fees from Abbvie, Amgen, Bristol-Myers Squibb, CRC Oncology, Genentech, Roche, and Sanofi, and has received grant funding from AstraZeneca and Bristol Myers Squib. Dr. Deswal and Dr. Witteles had no relevant disclosures.
AT ACC 2023