Hypertension

The addition of aspirin to standard guideline management for blood pressure did not reduce the risk of cardiovascular events among adults with hypertension and controlled systolic blood pressure in a study.

The benefits of aspirin use for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) have been questioned in light of data showing neutral outcomes in low-risk patients and concerns about increased bleeding risk and mortality in healthy older adults, wrote Rita Del Pinto, MD, of University of L’Aquila (Italy) and colleagues in JAMA Network Open.

In the study, Dr. Del Pinto and colleagues conducted a post hoc analysis of data from more than 2,500 participants in SPRINT (Systolic Blood Pressure Intervention Trial), a multicenter, randomized trial conducted from 2010 to 2013.

The goal of SPRINT was to compare intensive and standard blood pressure–lowering strategies for hypertension patients. The primary outcome of the current study was risk of a first cardiovascular event, which included adjudicated myocardial infarction, non–myocardial infarction acute coronary syndrome, stroke, acute heart failure, and CVD death.“There has been considerable improvement in the management of cardiovascular risk factors since the first reports on aspirin use for cardiovascular prevention,” Dr. Del Pinto said in an interview.

“As for hypertension, not only have more effective antihypertensive medications become available, but also evidence has recently emerged in support of a downwards redefinition of blood pressure targets during treatment,” she said. “In this context, in an era when great attention is paid to the personalization of treatment, no specific studies had addressed the association of aspirin use as a primary prevention strategy in a cohort of relatively old, high-risk individuals with treated systolic blood pressure steadily below the recommended target,” she added.

The researchers assessed whether aspirin use in addition to standard blood pressure management (a target of less than 140 mm Hg) decreased risk and improved survival.

The study population included 2,664 adult patients; 29.3% were women, and 24.5% were aged 75 years and older. Half of the patients (1,332) received aspirin and 1,332 did not.

In a multivariate analysis, 42 cardiovascular events occurred in the aspirin group, compared with 20 events in those not exposed to aspirin (hazard ratio, 2.30). The findings were consistent in subgroup analyses of younger individuals, current and former smokers, and patients on statins.

An additional subgroup analysis of individuals randomized to standard care or intensive care in the SPRINT study showed no significant difference in primary outcome rates between individuals who received aspirin and those who did not. The rates for aspirin use vs. non–aspirin use were 5.85% vs. 3.60% in the standard treatment group and 4.66% vs. 2.56% in the intensive treatment group.

The study findings were limited by several factors, including the post hoc design, short follow-up period, and lack of data on the initiation of aspirin and bleeding events, the researchers wrote. However, the results suggest that modern management of hypertension may have redefined the potential benefits of aspirin in patients with hypertension, they concluded.

Findings confirm value of preventive care

“The study was conducted as a post-hoc analysis on an experimental cohort, which must be considered when interpreting the results,” Dr. Del Pinto said.

Despite the limitations, the study findings affirm that effective treatment of major cardiovascular risk factors, such as hypertension, with proven drugs is “a mainstay of the primary prevention of ASCVD,” she emphasized.

As for additional research, “Testing our findings in a dedicated setting with sufficiently long follow-up, where aspirin dose and indication, as well as any possible bleeding event, are reported could expand the clinical meaning of our observations,” said Dr. Del Pinto. “Also, the clinical impact of aspirin, even in combination with novel cardiovascular drugs such as direct oral anticoagulants, in populations exposed to combinations of risk factors, deserves further investigation.”

Data support shared decision-making

“While recent evidence has not shown a benefit of aspirin in the primary prevention of ASCVD in several populations, the subpopulation of patients with hypertension as an ASCVD risk factor is also of interest to the clinician,” Suman Pal, MD, of the University of New Mexico, Albuquerque, said in an interview. “The lack of benefit of aspirin in this study, despite its limitations, was surprising, and I would be eager to see how the role of aspirin in ASCVD prevention would continue to evolve in conjunction with improvement in other therapies for modification of risk factors.”

“The decision to continue aspirin in this subgroup of patients should warrant a discussion with patients and a reexamination of risks and benefits until further data are available,” Dr. Pal emphasized. 

Larger studies with long-term follow-ups would be required to further clarify the role of aspirin in primary prevention of ASCVD in patients with hypertension without diabetes or chronic kidney disease, he added.

Data were supplied courtesy of BioLINCC. The study received no outside funding. The researchers and Dr. Pal had no financial conflicts to disclose.

The addition of aspirin to standard guideline management for blood pressure did not reduce the risk of cardiovascular events among adults with hypertension and controlled systolic blood pressure in a study.

The benefits of aspirin use for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) have been questioned in light of data showing neutral outcomes in low-risk patients and concerns about increased bleeding risk and mortality in healthy older adults, wrote Rita Del Pinto, MD, of University of L’Aquila (Italy) and colleagues in JAMA Network Open.

In the study, Dr. Del Pinto and colleagues conducted a post hoc analysis of data from more than 2,500 participants in SPRINT (Systolic Blood Pressure Intervention Trial), a multicenter, randomized trial conducted from 2010 to 2013.

The goal of SPRINT was to compare intensive and standard blood pressure–lowering strategies for hypertension patients. The primary outcome of the current study was risk of a first cardiovascular event, which included adjudicated myocardial infarction, non–myocardial infarction acute coronary syndrome, stroke, acute heart failure, and CVD death.“There has been considerable improvement in the management of cardiovascular risk factors since the first reports on aspirin use for cardiovascular prevention,” Dr. Del Pinto said in an interview.

“As for hypertension, not only have more effective antihypertensive medications become available, but also evidence has recently emerged in support of a downwards redefinition of blood pressure targets during treatment,” she said. “In this context, in an era when great attention is paid to the personalization of treatment, no specific studies had addressed the association of aspirin use as a primary prevention strategy in a cohort of relatively old, high-risk individuals with treated systolic blood pressure steadily below the recommended target,” she added.

The researchers assessed whether aspirin use in addition to standard blood pressure management (a target of less than 140 mm Hg) decreased risk and improved survival.

The study population included 2,664 adult patients; 29.3% were women, and 24.5% were aged 75 years and older. Half of the patients (1,332) received aspirin and 1,332 did not.

In a multivariate analysis, 42 cardiovascular events occurred in the aspirin group, compared with 20 events in those not exposed to aspirin (hazard ratio, 2.30). The findings were consistent in subgroup analyses of younger individuals, current and former smokers, and patients on statins.

An additional subgroup analysis of individuals randomized to standard care or intensive care in the SPRINT study showed no significant difference in primary outcome rates between individuals who received aspirin and those who did not. The rates for aspirin use vs. non–aspirin use were 5.85% vs. 3.60% in the standard treatment group and 4.66% vs. 2.56% in the intensive treatment group.

The study findings were limited by several factors, including the post hoc design, short follow-up period, and lack of data on the initiation of aspirin and bleeding events, the researchers wrote. However, the results suggest that modern management of hypertension may have redefined the potential benefits of aspirin in patients with hypertension, they concluded.

Findings confirm value of preventive care

“The study was conducted as a post-hoc analysis on an experimental cohort, which must be considered when interpreting the results,” Dr. Del Pinto said.

Despite the limitations, the study findings affirm that effective treatment of major cardiovascular risk factors, such as hypertension, with proven drugs is “a mainstay of the primary prevention of ASCVD,” she emphasized.

As for additional research, “Testing our findings in a dedicated setting with sufficiently long follow-up, where aspirin dose and indication, as well as any possible bleeding event, are reported could expand the clinical meaning of our observations,” said Dr. Del Pinto. “Also, the clinical impact of aspirin, even in combination with novel cardiovascular drugs such as direct oral anticoagulants, in populations exposed to combinations of risk factors, deserves further investigation.”

Data support shared decision-making

“While recent evidence has not shown a benefit of aspirin in the primary prevention of ASCVD in several populations, the subpopulation of patients with hypertension as an ASCVD risk factor is also of interest to the clinician,” Suman Pal, MD, of the University of New Mexico, Albuquerque, said in an interview. “The lack of benefit of aspirin in this study, despite its limitations, was surprising, and I would be eager to see how the role of aspirin in ASCVD prevention would continue to evolve in conjunction with improvement in other therapies for modification of risk factors.”

“The decision to continue aspirin in this subgroup of patients should warrant a discussion with patients and a reexamination of risks and benefits until further data are available,” Dr. Pal emphasized. 

Larger studies with long-term follow-ups would be required to further clarify the role of aspirin in primary prevention of ASCVD in patients with hypertension without diabetes or chronic kidney disease, he added.

Data were supplied courtesy of BioLINCC. The study received no outside funding. The researchers and Dr. Pal had no financial conflicts to disclose.

The addition of aspirin to standard guideline management for blood pressure did not reduce the risk of cardiovascular events among adults with hypertension and controlled systolic blood pressure in a study.

The benefits of aspirin use for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) have been questioned in light of data showing neutral outcomes in low-risk patients and concerns about increased bleeding risk and mortality in healthy older adults, wrote Rita Del Pinto, MD, of University of L’Aquila (Italy) and colleagues in JAMA Network Open.

In the study, Dr. Del Pinto and colleagues conducted a post hoc analysis of data from more than 2,500 participants in SPRINT (Systolic Blood Pressure Intervention Trial), a multicenter, randomized trial conducted from 2010 to 2013.

The goal of SPRINT was to compare intensive and standard blood pressure–lowering strategies for hypertension patients. The primary outcome of the current study was risk of a first cardiovascular event, which included adjudicated myocardial infarction, non–myocardial infarction acute coronary syndrome, stroke, acute heart failure, and CVD death.“There has been considerable improvement in the management of cardiovascular risk factors since the first reports on aspirin use for cardiovascular prevention,” Dr. Del Pinto said in an interview.

“As for hypertension, not only have more effective antihypertensive medications become available, but also evidence has recently emerged in support of a downwards redefinition of blood pressure targets during treatment,” she said. “In this context, in an era when great attention is paid to the personalization of treatment, no specific studies had addressed the association of aspirin use as a primary prevention strategy in a cohort of relatively old, high-risk individuals with treated systolic blood pressure steadily below the recommended target,” she added.

The researchers assessed whether aspirin use in addition to standard blood pressure management (a target of less than 140 mm Hg) decreased risk and improved survival.

The study population included 2,664 adult patients; 29.3% were women, and 24.5% were aged 75 years and older. Half of the patients (1,332) received aspirin and 1,332 did not.

In a multivariate analysis, 42 cardiovascular events occurred in the aspirin group, compared with 20 events in those not exposed to aspirin (hazard ratio, 2.30). The findings were consistent in subgroup analyses of younger individuals, current and former smokers, and patients on statins.

An additional subgroup analysis of individuals randomized to standard care or intensive care in the SPRINT study showed no significant difference in primary outcome rates between individuals who received aspirin and those who did not. The rates for aspirin use vs. non–aspirin use were 5.85% vs. 3.60% in the standard treatment group and 4.66% vs. 2.56% in the intensive treatment group.

The study findings were limited by several factors, including the post hoc design, short follow-up period, and lack of data on the initiation of aspirin and bleeding events, the researchers wrote. However, the results suggest that modern management of hypertension may have redefined the potential benefits of aspirin in patients with hypertension, they concluded.

Findings confirm value of preventive care

“The study was conducted as a post-hoc analysis on an experimental cohort, which must be considered when interpreting the results,” Dr. Del Pinto said.

Despite the limitations, the study findings affirm that effective treatment of major cardiovascular risk factors, such as hypertension, with proven drugs is “a mainstay of the primary prevention of ASCVD,” she emphasized.

As for additional research, “Testing our findings in a dedicated setting with sufficiently long follow-up, where aspirin dose and indication, as well as any possible bleeding event, are reported could expand the clinical meaning of our observations,” said Dr. Del Pinto. “Also, the clinical impact of aspirin, even in combination with novel cardiovascular drugs such as direct oral anticoagulants, in populations exposed to combinations of risk factors, deserves further investigation.”

Data support shared decision-making

“While recent evidence has not shown a benefit of aspirin in the primary prevention of ASCVD in several populations, the subpopulation of patients with hypertension as an ASCVD risk factor is also of interest to the clinician,” Suman Pal, MD, of the University of New Mexico, Albuquerque, said in an interview. “The lack of benefit of aspirin in this study, despite its limitations, was surprising, and I would be eager to see how the role of aspirin in ASCVD prevention would continue to evolve in conjunction with improvement in other therapies for modification of risk factors.”

“The decision to continue aspirin in this subgroup of patients should warrant a discussion with patients and a reexamination of risks and benefits until further data are available,” Dr. Pal emphasized. 

Larger studies with long-term follow-ups would be required to further clarify the role of aspirin in primary prevention of ASCVD in patients with hypertension without diabetes or chronic kidney disease, he added.

Data were supplied courtesy of BioLINCC. The study received no outside funding. The researchers and Dr. Pal had no financial conflicts to disclose.

Radiofrequency renal denervation provided progressive reductions in blood pressure at 3 years in patients on antihypertensive medication, but this did not translate into fewer antihypertensive drugs, new results from the SPYRAL HTN-ON MED trial show.

At 36 months, 24-hour ambulatory systolic and diastolic blood pressures were 10.0 mm Hg (P = .003) and 5.9 mm Hg (P = .005) lower, respectively, in patients who underwent renal denervation with Medtronic’s Symplicity Spyral radiofrequency catheter, compared with patients treated with a sham procedure.

The number of antihypertensive drugs, however, increased in both groups from an average of two at baseline and 6 months to three at 3 years (P = .76).

Based on the number of drugs, class, and dose, medication burden increased significantly in the sham group at 12 months (6.5 vs. 4.9; P = .04) and trended higher at 3 years (10.3 vs. 7.6; P = .26).

The procedure appeared safe, with no renal safety events in the denervation group and only three safety events overall at 36 months. One cardiovascular death occurred 693 days after a sham procedure and one patient had a hypertensive crisis and stroke 427 days after renal denervation and was discharged in stable condition, according to results published in The Lancet.

“Given the long-term safety and efficacy of renal denervation, it may provide an alternative adjunctive treatment modality in the management of hypertension,” Felix Mahfoud, MD, Saarland University Hospital, Homburg, Germany, said during a presentation of the study at the recent American College of Cardiology (ACC) 2022 Scientific Session.

Ted Bosworth/MDedge News

Sham-controlled evidence

As previously reported, significant BP reductions at 6 months in SPYRAL HTN-ON provided proof of concept and helped revive enthusiasm for the procedure after failing to meet the primary endpoint in the SYMPLICITY HTN-3 trial. Results from the Global SYMPLICITY Registry have shown benefits out to 3 years, but sham-controlled data have been lacking.

The trial enrolled 80 patients with an office systolic BP of 150-180 mm Hg and diastolic of 90 mm Hg or greater and 24-hour ambulatory systolic BP of 140-170 mm Hg, who were on up to three antihypertensive medications.

Medication changes were allowed beginning at 6 months; patients and physicians were unblinded at 12 months. Between 24 and 36 months, 13 patients assigned to the sham procedure crossed over to denervation treatment. Medication adherence at 3 years was 77% in the denervation group versus 93% in the sham group.

At 3 years, the renal denervation group had significantly greater reductions from baseline in several ambulatory BP measures, compared with the sham group, including: 24-hour systolic (10.0 mm Hg), morning systolic (11.0 mm Hg), daytime systolic (8.9 mm Hg), and night-time systolic (11.8 mm Hg).

Renal denervation led to an 8.2 mm Hg greater fall in office systolic BP, but this failed to reach statistical significance (P = .07).

Almost twice as many patients in the denervation group achieved a 24-hour systolic BP less than 140 mm Hg than in the sham group (83.3%, vs. 43.8%; P = .002), Dr. Mahfoud reported.

“Although renal denervation appears to effectively lower blood pressure, participants in the renal denervation group did not quite reach guideline-recommended blood pressure thresholds,” Harini Sarathy, MD, University of California, San Francisco, and Liann Abu Salman, MD, Perelman School of Medicine, University of Pennsylvania, Philadelphia, point out in an accompanying editorial. “This result could have been due to a degree of physician inertia or differential prescribing of blood pressure medications for the intervention group, compared with the sham control group, wherein physicians might have considered renal denervation to be the fourth antihypertensive medication.”

The editorialists also note that nearly a third of the sham group (13 of 42) underwent renal denervation. “The differentially missing BP readings at 24 months for the sham group are a cause for concern, although the absence of any meaningful differences in results after imputation is somewhat reassuring.”

A 10 mm Hg reduction in BP after 36 months would be expected to translate to a significant reduction in cardiovascular outcomes, they say. The sustained reductions in several systolic readings also speak to the “always-on distinctiveness” that renal denervation proponents claim.

“In the stark absence of novel antihypertensive drug development, renal denervation is seemingly poised to be an effective supplement, if not an alternative, to complex antihypertensive regimens with frequent dosing schedules,” they conclude. “We look forward to results of the Expansion trial in providing more definitive answers regarding whether this translates to meaningful protection from target organ damage.”

Dr. Mahfoud observed that BP control worsened during the COVID-19 pandemic, which may have impacted BP results, but that in-person follow-up visits were still performed. Other limitations are a lack of information on patients’ exercise, diet, and smoking habits and that blood and urine testing assessed medication adherence at discrete time points, but adherence over an extended period of time is uncertain.

Dr. Mahfoud reports research grants from Deutsche Forschungsgemeinschaft and Deutsche Gesellschaft für Kardiologie and scientific support and speaker honoraria from Bayer, Boehringer Ingelheim, Medtronic, Merck, and ReCor Medical. The study was funded by Medtronic. Dr. Sarathy and Dr. Salman report no relevant financial relationships.

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

Radiofrequency renal denervation provided progressive reductions in blood pressure at 3 years in patients on antihypertensive medication, but this did not translate into fewer antihypertensive drugs, new results from the SPYRAL HTN-ON MED trial show.

At 36 months, 24-hour ambulatory systolic and diastolic blood pressures were 10.0 mm Hg (P = .003) and 5.9 mm Hg (P = .005) lower, respectively, in patients who underwent renal denervation with Medtronic’s Symplicity Spyral radiofrequency catheter, compared with patients treated with a sham procedure.

The number of antihypertensive drugs, however, increased in both groups from an average of two at baseline and 6 months to three at 3 years (P = .76).

Based on the number of drugs, class, and dose, medication burden increased significantly in the sham group at 12 months (6.5 vs. 4.9; P = .04) and trended higher at 3 years (10.3 vs. 7.6; P = .26).

The procedure appeared safe, with no renal safety events in the denervation group and only three safety events overall at 36 months. One cardiovascular death occurred 693 days after a sham procedure and one patient had a hypertensive crisis and stroke 427 days after renal denervation and was discharged in stable condition, according to results published in The Lancet.

“Given the long-term safety and efficacy of renal denervation, it may provide an alternative adjunctive treatment modality in the management of hypertension,” Felix Mahfoud, MD, Saarland University Hospital, Homburg, Germany, said during a presentation of the study at the recent American College of Cardiology (ACC) 2022 Scientific Session.

Ted Bosworth/MDedge News

Sham-controlled evidence

As previously reported, significant BP reductions at 6 months in SPYRAL HTN-ON provided proof of concept and helped revive enthusiasm for the procedure after failing to meet the primary endpoint in the SYMPLICITY HTN-3 trial. Results from the Global SYMPLICITY Registry have shown benefits out to 3 years, but sham-controlled data have been lacking.

The trial enrolled 80 patients with an office systolic BP of 150-180 mm Hg and diastolic of 90 mm Hg or greater and 24-hour ambulatory systolic BP of 140-170 mm Hg, who were on up to three antihypertensive medications.

Medication changes were allowed beginning at 6 months; patients and physicians were unblinded at 12 months. Between 24 and 36 months, 13 patients assigned to the sham procedure crossed over to denervation treatment. Medication adherence at 3 years was 77% in the denervation group versus 93% in the sham group.

At 3 years, the renal denervation group had significantly greater reductions from baseline in several ambulatory BP measures, compared with the sham group, including: 24-hour systolic (10.0 mm Hg), morning systolic (11.0 mm Hg), daytime systolic (8.9 mm Hg), and night-time systolic (11.8 mm Hg).

Renal denervation led to an 8.2 mm Hg greater fall in office systolic BP, but this failed to reach statistical significance (P = .07).

Almost twice as many patients in the denervation group achieved a 24-hour systolic BP less than 140 mm Hg than in the sham group (83.3%, vs. 43.8%; P = .002), Dr. Mahfoud reported.

“Although renal denervation appears to effectively lower blood pressure, participants in the renal denervation group did not quite reach guideline-recommended blood pressure thresholds,” Harini Sarathy, MD, University of California, San Francisco, and Liann Abu Salman, MD, Perelman School of Medicine, University of Pennsylvania, Philadelphia, point out in an accompanying editorial. “This result could have been due to a degree of physician inertia or differential prescribing of blood pressure medications for the intervention group, compared with the sham control group, wherein physicians might have considered renal denervation to be the fourth antihypertensive medication.”

The editorialists also note that nearly a third of the sham group (13 of 42) underwent renal denervation. “The differentially missing BP readings at 24 months for the sham group are a cause for concern, although the absence of any meaningful differences in results after imputation is somewhat reassuring.”

A 10 mm Hg reduction in BP after 36 months would be expected to translate to a significant reduction in cardiovascular outcomes, they say. The sustained reductions in several systolic readings also speak to the “always-on distinctiveness” that renal denervation proponents claim.

“In the stark absence of novel antihypertensive drug development, renal denervation is seemingly poised to be an effective supplement, if not an alternative, to complex antihypertensive regimens with frequent dosing schedules,” they conclude. “We look forward to results of the Expansion trial in providing more definitive answers regarding whether this translates to meaningful protection from target organ damage.”

Dr. Mahfoud observed that BP control worsened during the COVID-19 pandemic, which may have impacted BP results, but that in-person follow-up visits were still performed. Other limitations are a lack of information on patients’ exercise, diet, and smoking habits and that blood and urine testing assessed medication adherence at discrete time points, but adherence over an extended period of time is uncertain.

Dr. Mahfoud reports research grants from Deutsche Forschungsgemeinschaft and Deutsche Gesellschaft für Kardiologie and scientific support and speaker honoraria from Bayer, Boehringer Ingelheim, Medtronic, Merck, and ReCor Medical. The study was funded by Medtronic. Dr. Sarathy and Dr. Salman report no relevant financial relationships.

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

Radiofrequency renal denervation provided progressive reductions in blood pressure at 3 years in patients on antihypertensive medication, but this did not translate into fewer antihypertensive drugs, new results from the SPYRAL HTN-ON MED trial show.

At 36 months, 24-hour ambulatory systolic and diastolic blood pressures were 10.0 mm Hg (P = .003) and 5.9 mm Hg (P = .005) lower, respectively, in patients who underwent renal denervation with Medtronic’s Symplicity Spyral radiofrequency catheter, compared with patients treated with a sham procedure.

The number of antihypertensive drugs, however, increased in both groups from an average of two at baseline and 6 months to three at 3 years (P = .76).

Based on the number of drugs, class, and dose, medication burden increased significantly in the sham group at 12 months (6.5 vs. 4.9; P = .04) and trended higher at 3 years (10.3 vs. 7.6; P = .26).

The procedure appeared safe, with no renal safety events in the denervation group and only three safety events overall at 36 months. One cardiovascular death occurred 693 days after a sham procedure and one patient had a hypertensive crisis and stroke 427 days after renal denervation and was discharged in stable condition, according to results published in The Lancet.

“Given the long-term safety and efficacy of renal denervation, it may provide an alternative adjunctive treatment modality in the management of hypertension,” Felix Mahfoud, MD, Saarland University Hospital, Homburg, Germany, said during a presentation of the study at the recent American College of Cardiology (ACC) 2022 Scientific Session.

Ted Bosworth/MDedge News

Sham-controlled evidence

As previously reported, significant BP reductions at 6 months in SPYRAL HTN-ON provided proof of concept and helped revive enthusiasm for the procedure after failing to meet the primary endpoint in the SYMPLICITY HTN-3 trial. Results from the Global SYMPLICITY Registry have shown benefits out to 3 years, but sham-controlled data have been lacking.

The trial enrolled 80 patients with an office systolic BP of 150-180 mm Hg and diastolic of 90 mm Hg or greater and 24-hour ambulatory systolic BP of 140-170 mm Hg, who were on up to three antihypertensive medications.

Medication changes were allowed beginning at 6 months; patients and physicians were unblinded at 12 months. Between 24 and 36 months, 13 patients assigned to the sham procedure crossed over to denervation treatment. Medication adherence at 3 years was 77% in the denervation group versus 93% in the sham group.

At 3 years, the renal denervation group had significantly greater reductions from baseline in several ambulatory BP measures, compared with the sham group, including: 24-hour systolic (10.0 mm Hg), morning systolic (11.0 mm Hg), daytime systolic (8.9 mm Hg), and night-time systolic (11.8 mm Hg).

Renal denervation led to an 8.2 mm Hg greater fall in office systolic BP, but this failed to reach statistical significance (P = .07).

Almost twice as many patients in the denervation group achieved a 24-hour systolic BP less than 140 mm Hg than in the sham group (83.3%, vs. 43.8%; P = .002), Dr. Mahfoud reported.

“Although renal denervation appears to effectively lower blood pressure, participants in the renal denervation group did not quite reach guideline-recommended blood pressure thresholds,” Harini Sarathy, MD, University of California, San Francisco, and Liann Abu Salman, MD, Perelman School of Medicine, University of Pennsylvania, Philadelphia, point out in an accompanying editorial. “This result could have been due to a degree of physician inertia or differential prescribing of blood pressure medications for the intervention group, compared with the sham control group, wherein physicians might have considered renal denervation to be the fourth antihypertensive medication.”

The editorialists also note that nearly a third of the sham group (13 of 42) underwent renal denervation. “The differentially missing BP readings at 24 months for the sham group are a cause for concern, although the absence of any meaningful differences in results after imputation is somewhat reassuring.”

A 10 mm Hg reduction in BP after 36 months would be expected to translate to a significant reduction in cardiovascular outcomes, they say. The sustained reductions in several systolic readings also speak to the “always-on distinctiveness” that renal denervation proponents claim.

“In the stark absence of novel antihypertensive drug development, renal denervation is seemingly poised to be an effective supplement, if not an alternative, to complex antihypertensive regimens with frequent dosing schedules,” they conclude. “We look forward to results of the Expansion trial in providing more definitive answers regarding whether this translates to meaningful protection from target organ damage.”

Dr. Mahfoud observed that BP control worsened during the COVID-19 pandemic, which may have impacted BP results, but that in-person follow-up visits were still performed. Other limitations are a lack of information on patients’ exercise, diet, and smoking habits and that blood and urine testing assessed medication adherence at discrete time points, but adherence over an extended period of time is uncertain.

Dr. Mahfoud reports research grants from Deutsche Forschungsgemeinschaft and Deutsche Gesellschaft für Kardiologie and scientific support and speaker honoraria from Bayer, Boehringer Ingelheim, Medtronic, Merck, and ReCor Medical. The study was funded by Medtronic. Dr. Sarathy and Dr. Salman report no relevant financial relationships.

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

A genetic risk score based on blood pressure has been shown to potentially help determine the increased risk for heart attack or stroke in people with type 2 diabetes, suggesting that glucose control alone won’t be enough to control a person’s genetic risk for other cardiometabolic diseases.

The study analyzed genetic data from 6,335 participants, characterized as a high-risk multiethnic type 2 diabetes population, in the Action to Control Cardiovascular Risk in Diabetes study (ACCORD). Investigators developed a multivariable-adjustable model that found that, with each degree increase in the genetic score, the risk of cardiovascular disease (CVD) events increased 12%. However, the study found no relationship between glycemic control therapy and BP genetic risk score in CVD risk (P < .10).

Researchers at the University of Alabama at Birmingham reported on the risk score in a research letter

“This study highlights that commonly occurring changes in our DNA that cumulatively contribute to a higher risk of BP and hypertension can predispose T2DM [type 2 diabetes mellitus] patients to a higher risk of CVD events,” lead author Pankaj Arora, MD, said in a comment. The genetic risk score used in the study was effective at identifying CVD risks among the study participants even after accounting for conventional CV risk factors, added Dr. Arora, who’s director of the cardiovascular clinical and translational research and cardiovascular genetics clinic programs at UAB. “We recognize that cardiometabolic diseases travel together. Simply controlling the blood glucose level in isolation without considering an individual’s genetic risk for other cardiometabolic diseases may not yield a reduction of CVD risk in T2DM.”

The study used a map of more than 1,000 common genetic variants known to affect BP and compared that with the DNA of study participants to determine their genetic risks. Dr. Arora and colleagues wrote that the “results invigorate the potential implications” of using a BP polygenic risk score to address CVD risks through early intervention with lifestyle modifications such as diet, exercise, smoking cessation, weight management, and BP control in people with high genetic risk.

Gene profiles like the model the UAB researchers developed are still far away from the clinic, Dr. Arora said. “While such gene profiles are being used regularly in cancer management, these gene profiles are not easily available for cardiologists and endocrinologists to order.” He noted that the cardiogenomics clinic at UAB is one of the few centers that provide this kind of gene profiling in the United States. “Studies like this are bringing gene profiling closer to the doorstep of all cardiology and endocrinology clinics.”

The next step for the research is to expand the genetic variants used in the profiles. “We are now trying to develop a gene profile that encompasses more than 1 million common genetic variations and will be more informative,” Dr. Arora said. He added that few randomized clinical trials have shown using a BP genetic risk score in the clinic would improve outcomes of people with T2DM.

Peggy Peterson Photograph

Kiran Musunuru, MD, PhD, MPH, director of the genetic and epigenetic origins of disease program at the University of Pennsylvania’s cardiovascular program in Philadelphia, provided context on what the study adds to the understanding of CVD risk in people with T2DM. “We know that patients with type 2 diabetes are at increased risk of cardiovascular disease, some of which is due to coexisting risk factors like abnormal lipids and hypertension,” he said in a comment. “This study shows that genetic predisposition to high blood pressure is one of the drivers of risk in these patients.” Dr. Musunuru is also chair of the writing group for the American Heart Association scientific statement on the use of genetics and genomics in clinical care.

However, he noted that collecting that kind of genetic data is challenging because few companies offer the tests and few centers do routine genetic testing. “As more studies like this one demonstrate the potential benefits of genetic testing, we can expect to see broader adoption by clinicians,” Dr. Musunuru said.

Dr. Arora receives funding from the National Heart, Lung, and Blood Institute and the Doris Duke Charitable Foundation. The ACCORD study received funding from Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca, Bayer, Closer Healthcare, GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Merck, Novartis, Novo Nordisk, Omron Healthcare, Sanofi-Aventis US, and Schering-Plough. Dr. Musunuru has no relevant relationships to disclose.


 

A genetic risk score based on blood pressure has been shown to potentially help determine the increased risk for heart attack or stroke in people with type 2 diabetes, suggesting that glucose control alone won’t be enough to control a person’s genetic risk for other cardiometabolic diseases.

The study analyzed genetic data from 6,335 participants, characterized as a high-risk multiethnic type 2 diabetes population, in the Action to Control Cardiovascular Risk in Diabetes study (ACCORD). Investigators developed a multivariable-adjustable model that found that, with each degree increase in the genetic score, the risk of cardiovascular disease (CVD) events increased 12%. However, the study found no relationship between glycemic control therapy and BP genetic risk score in CVD risk (P < .10).

Researchers at the University of Alabama at Birmingham reported on the risk score in a research letter

“This study highlights that commonly occurring changes in our DNA that cumulatively contribute to a higher risk of BP and hypertension can predispose T2DM [type 2 diabetes mellitus] patients to a higher risk of CVD events,” lead author Pankaj Arora, MD, said in a comment. The genetic risk score used in the study was effective at identifying CVD risks among the study participants even after accounting for conventional CV risk factors, added Dr. Arora, who’s director of the cardiovascular clinical and translational research and cardiovascular genetics clinic programs at UAB. “We recognize that cardiometabolic diseases travel together. Simply controlling the blood glucose level in isolation without considering an individual’s genetic risk for other cardiometabolic diseases may not yield a reduction of CVD risk in T2DM.”

The study used a map of more than 1,000 common genetic variants known to affect BP and compared that with the DNA of study participants to determine their genetic risks. Dr. Arora and colleagues wrote that the “results invigorate the potential implications” of using a BP polygenic risk score to address CVD risks through early intervention with lifestyle modifications such as diet, exercise, smoking cessation, weight management, and BP control in people with high genetic risk.

Gene profiles like the model the UAB researchers developed are still far away from the clinic, Dr. Arora said. “While such gene profiles are being used regularly in cancer management, these gene profiles are not easily available for cardiologists and endocrinologists to order.” He noted that the cardiogenomics clinic at UAB is one of the few centers that provide this kind of gene profiling in the United States. “Studies like this are bringing gene profiling closer to the doorstep of all cardiology and endocrinology clinics.”

The next step for the research is to expand the genetic variants used in the profiles. “We are now trying to develop a gene profile that encompasses more than 1 million common genetic variations and will be more informative,” Dr. Arora said. He added that few randomized clinical trials have shown using a BP genetic risk score in the clinic would improve outcomes of people with T2DM.

Peggy Peterson Photograph

Kiran Musunuru, MD, PhD, MPH, director of the genetic and epigenetic origins of disease program at the University of Pennsylvania’s cardiovascular program in Philadelphia, provided context on what the study adds to the understanding of CVD risk in people with T2DM. “We know that patients with type 2 diabetes are at increased risk of cardiovascular disease, some of which is due to coexisting risk factors like abnormal lipids and hypertension,” he said in a comment. “This study shows that genetic predisposition to high blood pressure is one of the drivers of risk in these patients.” Dr. Musunuru is also chair of the writing group for the American Heart Association scientific statement on the use of genetics and genomics in clinical care.

However, he noted that collecting that kind of genetic data is challenging because few companies offer the tests and few centers do routine genetic testing. “As more studies like this one demonstrate the potential benefits of genetic testing, we can expect to see broader adoption by clinicians,” Dr. Musunuru said.

Dr. Arora receives funding from the National Heart, Lung, and Blood Institute and the Doris Duke Charitable Foundation. The ACCORD study received funding from Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca, Bayer, Closer Healthcare, GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Merck, Novartis, Novo Nordisk, Omron Healthcare, Sanofi-Aventis US, and Schering-Plough. Dr. Musunuru has no relevant relationships to disclose.


 

A genetic risk score based on blood pressure has been shown to potentially help determine the increased risk for heart attack or stroke in people with type 2 diabetes, suggesting that glucose control alone won’t be enough to control a person’s genetic risk for other cardiometabolic diseases.

The study analyzed genetic data from 6,335 participants, characterized as a high-risk multiethnic type 2 diabetes population, in the Action to Control Cardiovascular Risk in Diabetes study (ACCORD). Investigators developed a multivariable-adjustable model that found that, with each degree increase in the genetic score, the risk of cardiovascular disease (CVD) events increased 12%. However, the study found no relationship between glycemic control therapy and BP genetic risk score in CVD risk (P < .10).

Researchers at the University of Alabama at Birmingham reported on the risk score in a research letter

“This study highlights that commonly occurring changes in our DNA that cumulatively contribute to a higher risk of BP and hypertension can predispose T2DM [type 2 diabetes mellitus] patients to a higher risk of CVD events,” lead author Pankaj Arora, MD, said in a comment. The genetic risk score used in the study was effective at identifying CVD risks among the study participants even after accounting for conventional CV risk factors, added Dr. Arora, who’s director of the cardiovascular clinical and translational research and cardiovascular genetics clinic programs at UAB. “We recognize that cardiometabolic diseases travel together. Simply controlling the blood glucose level in isolation without considering an individual’s genetic risk for other cardiometabolic diseases may not yield a reduction of CVD risk in T2DM.”

The study used a map of more than 1,000 common genetic variants known to affect BP and compared that with the DNA of study participants to determine their genetic risks. Dr. Arora and colleagues wrote that the “results invigorate the potential implications” of using a BP polygenic risk score to address CVD risks through early intervention with lifestyle modifications such as diet, exercise, smoking cessation, weight management, and BP control in people with high genetic risk.

Gene profiles like the model the UAB researchers developed are still far away from the clinic, Dr. Arora said. “While such gene profiles are being used regularly in cancer management, these gene profiles are not easily available for cardiologists and endocrinologists to order.” He noted that the cardiogenomics clinic at UAB is one of the few centers that provide this kind of gene profiling in the United States. “Studies like this are bringing gene profiling closer to the doorstep of all cardiology and endocrinology clinics.”

The next step for the research is to expand the genetic variants used in the profiles. “We are now trying to develop a gene profile that encompasses more than 1 million common genetic variations and will be more informative,” Dr. Arora said. He added that few randomized clinical trials have shown using a BP genetic risk score in the clinic would improve outcomes of people with T2DM.

Peggy Peterson Photograph

Kiran Musunuru, MD, PhD, MPH, director of the genetic and epigenetic origins of disease program at the University of Pennsylvania’s cardiovascular program in Philadelphia, provided context on what the study adds to the understanding of CVD risk in people with T2DM. “We know that patients with type 2 diabetes are at increased risk of cardiovascular disease, some of which is due to coexisting risk factors like abnormal lipids and hypertension,” he said in a comment. “This study shows that genetic predisposition to high blood pressure is one of the drivers of risk in these patients.” Dr. Musunuru is also chair of the writing group for the American Heart Association scientific statement on the use of genetics and genomics in clinical care.

However, he noted that collecting that kind of genetic data is challenging because few companies offer the tests and few centers do routine genetic testing. “As more studies like this one demonstrate the potential benefits of genetic testing, we can expect to see broader adoption by clinicians,” Dr. Musunuru said.

Dr. Arora receives funding from the National Heart, Lung, and Blood Institute and the Doris Duke Charitable Foundation. The ACCORD study received funding from Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca, Bayer, Closer Healthcare, GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Merck, Novartis, Novo Nordisk, Omron Healthcare, Sanofi-Aventis US, and Schering-Plough. Dr. Musunuru has no relevant relationships to disclose.


 

WASHINGTON – Patients with heart failure who received an annual influenza vaccine for 3 years running had significantly fewer all-cause hospitalizations and significantly fewer cases of pneumonia during that time, compared with placebo-treated patients with heart failure, in a prospective, randomized, global trial with 5,129 participants.

Although the results failed to show a significant reduction in all-cause deaths linked to influenza vaccination, compared with controls during the entire 3 years of the study, the results did show a significant 21% relative mortality-risk reduction by vaccination during periods of peak influenza circulation, and a significant 23% reduction in cardiovascular deaths, compared with controls during peak seasons.

courtesy Dr. Mark Loeb

“This is the first randomized, controlled trial of influenza vaccine in patients with heart failure, and we showed that vaccination reduces deaths” during peak influenza seasons, Mark Loeb, MD, said during a press briefing at the annual scientific sessions of the American College of Cardiology. The results send “an important global message that patients with heart failure should receive the influenza vaccine,” said Dr. Loeb, a professor at McMaster University, Hamilton, Ont., who specializes in clinical epidemiology and infectious diseases.

Dr. Loeb admitted that he and his associates erred when they picked the time window to assess the two primary endpoints for the trial: the combined rate of cardiovascular death, nonfatal MI, and nonfatal stroke, and this combined endpoint plus hospitalizations for heart failure.

The time window they selected was the entirety of all 3 years following three annual immunizations. That was a mistake.
 

No flu vaccine benefit outside flu season

“We know that the influenza vaccine will not have any effect outside of when influenza is circulating. In retrospect, we should have done that,” Dr. Loeb bemoaned during his talk. He chalked up the bad choice to concern over collecting enough endpoints to see a significant between-group difference when the researchers designed the study.

For the entire 3 years of follow-up, influenza vaccination was tied to a nonsignificant 7% relative risk reduction for the first primary endpoint, and a nonsignificant 9% relative risk reduction for the second primary endpoint, he reported.

But Dr. Loeb lobbied for the relevance of several significant secondary endpoints that collectively showed a compelling pattern of benefit during his talk. These included, for the full 3-years of follow-up, important, significant reductions relative to placebo of 16% for first all-cause hospitalizations (P = .01), and a 42% relative risk reduction in first cases of pneumonia (P = .0006).

Then there were the benefits that appeared during influenza season. In that analysis, first events for the first primary endpoint fell after vaccination by a significant 18% relative to placebo. The in-season analysis also showed the significant cuts in both all-cause and cardiovascular deaths.

Despite the neutral primary endpoints, “if you look at these data as a whole I think they speak to the importance of vaccinating patients with heart failure against influenza,” Dr. Loeb maintained.



‘Totality of evidence supports vaccination’

“I agree that the totality of evidence supports influenza vaccination,” commented Mark H. Drazner, MD, professor and clinical chief of cardiology at the University of Texas Southwestern Medical Center, Dallas, who was designated discussant for the report.

“The message should be to offer influenza vaccine to patients with heart failure,” Dr. Drazner said in an interview. “Previous data on influenza vaccine in patients with heart failure were largely observational. This was a randomized, prospective, placebo-controlled trial. That’s a step forward. Proving efficacy in a randomized trial is important.”

Dr Drazner added that his institution already promotes a “strong mandate” to vaccinate patients with heart failure against influenza.

“The influenza vaccine is a very effective and cost-efficient public health measure. Preventing hospitalizations of patients with heart failure has so many benefits,” commented Craig Beavers, PharmD, vice president of professional services at Baptist Health in Paducah, Ky., and a discussant during the press briefing.

Mitchel L. Zoler/MDedge News

The Influenza Vaccine To Prevent Adverse Vascular Events (IVVE) trial enrolled people with heart failure in New York Heart Association functional class II, III, or IV from any of 10 low- and middle-income countries including China, India, the Philippines, and multiple countries from Africa and the Middle East. They averaged 57 years of age, and slightly more than half were women.

IVVE was sponsored by McMaster University; the only commercial support that IVVE received was a free supply of influenza vaccine from Sanofi Pasteur. Dr. Loeb, Dr. Drazner, and Dr. Beavers had no disclosures.

WASHINGTON – Patients with heart failure who received an annual influenza vaccine for 3 years running had significantly fewer all-cause hospitalizations and significantly fewer cases of pneumonia during that time, compared with placebo-treated patients with heart failure, in a prospective, randomized, global trial with 5,129 participants.

Although the results failed to show a significant reduction in all-cause deaths linked to influenza vaccination, compared with controls during the entire 3 years of the study, the results did show a significant 21% relative mortality-risk reduction by vaccination during periods of peak influenza circulation, and a significant 23% reduction in cardiovascular deaths, compared with controls during peak seasons.

courtesy Dr. Mark Loeb

“This is the first randomized, controlled trial of influenza vaccine in patients with heart failure, and we showed that vaccination reduces deaths” during peak influenza seasons, Mark Loeb, MD, said during a press briefing at the annual scientific sessions of the American College of Cardiology. The results send “an important global message that patients with heart failure should receive the influenza vaccine,” said Dr. Loeb, a professor at McMaster University, Hamilton, Ont., who specializes in clinical epidemiology and infectious diseases.

Dr. Loeb admitted that he and his associates erred when they picked the time window to assess the two primary endpoints for the trial: the combined rate of cardiovascular death, nonfatal MI, and nonfatal stroke, and this combined endpoint plus hospitalizations for heart failure.

The time window they selected was the entirety of all 3 years following three annual immunizations. That was a mistake.
 

No flu vaccine benefit outside flu season

“We know that the influenza vaccine will not have any effect outside of when influenza is circulating. In retrospect, we should have done that,” Dr. Loeb bemoaned during his talk. He chalked up the bad choice to concern over collecting enough endpoints to see a significant between-group difference when the researchers designed the study.

For the entire 3 years of follow-up, influenza vaccination was tied to a nonsignificant 7% relative risk reduction for the first primary endpoint, and a nonsignificant 9% relative risk reduction for the second primary endpoint, he reported.

But Dr. Loeb lobbied for the relevance of several significant secondary endpoints that collectively showed a compelling pattern of benefit during his talk. These included, for the full 3-years of follow-up, important, significant reductions relative to placebo of 16% for first all-cause hospitalizations (P = .01), and a 42% relative risk reduction in first cases of pneumonia (P = .0006).

Then there were the benefits that appeared during influenza season. In that analysis, first events for the first primary endpoint fell after vaccination by a significant 18% relative to placebo. The in-season analysis also showed the significant cuts in both all-cause and cardiovascular deaths.

Despite the neutral primary endpoints, “if you look at these data as a whole I think they speak to the importance of vaccinating patients with heart failure against influenza,” Dr. Loeb maintained.



‘Totality of evidence supports vaccination’

“I agree that the totality of evidence supports influenza vaccination,” commented Mark H. Drazner, MD, professor and clinical chief of cardiology at the University of Texas Southwestern Medical Center, Dallas, who was designated discussant for the report.

“The message should be to offer influenza vaccine to patients with heart failure,” Dr. Drazner said in an interview. “Previous data on influenza vaccine in patients with heart failure were largely observational. This was a randomized, prospective, placebo-controlled trial. That’s a step forward. Proving efficacy in a randomized trial is important.”

Dr Drazner added that his institution already promotes a “strong mandate” to vaccinate patients with heart failure against influenza.

“The influenza vaccine is a very effective and cost-efficient public health measure. Preventing hospitalizations of patients with heart failure has so many benefits,” commented Craig Beavers, PharmD, vice president of professional services at Baptist Health in Paducah, Ky., and a discussant during the press briefing.

Mitchel L. Zoler/MDedge News

The Influenza Vaccine To Prevent Adverse Vascular Events (IVVE) trial enrolled people with heart failure in New York Heart Association functional class II, III, or IV from any of 10 low- and middle-income countries including China, India, the Philippines, and multiple countries from Africa and the Middle East. They averaged 57 years of age, and slightly more than half were women.

IVVE was sponsored by McMaster University; the only commercial support that IVVE received was a free supply of influenza vaccine from Sanofi Pasteur. Dr. Loeb, Dr. Drazner, and Dr. Beavers had no disclosures.

WASHINGTON – Patients with heart failure who received an annual influenza vaccine for 3 years running had significantly fewer all-cause hospitalizations and significantly fewer cases of pneumonia during that time, compared with placebo-treated patients with heart failure, in a prospective, randomized, global trial with 5,129 participants.

Although the results failed to show a significant reduction in all-cause deaths linked to influenza vaccination, compared with controls during the entire 3 years of the study, the results did show a significant 21% relative mortality-risk reduction by vaccination during periods of peak influenza circulation, and a significant 23% reduction in cardiovascular deaths, compared with controls during peak seasons.

courtesy Dr. Mark Loeb

“This is the first randomized, controlled trial of influenza vaccine in patients with heart failure, and we showed that vaccination reduces deaths” during peak influenza seasons, Mark Loeb, MD, said during a press briefing at the annual scientific sessions of the American College of Cardiology. The results send “an important global message that patients with heart failure should receive the influenza vaccine,” said Dr. Loeb, a professor at McMaster University, Hamilton, Ont., who specializes in clinical epidemiology and infectious diseases.

Dr. Loeb admitted that he and his associates erred when they picked the time window to assess the two primary endpoints for the trial: the combined rate of cardiovascular death, nonfatal MI, and nonfatal stroke, and this combined endpoint plus hospitalizations for heart failure.

The time window they selected was the entirety of all 3 years following three annual immunizations. That was a mistake.
 

No flu vaccine benefit outside flu season

“We know that the influenza vaccine will not have any effect outside of when influenza is circulating. In retrospect, we should have done that,” Dr. Loeb bemoaned during his talk. He chalked up the bad choice to concern over collecting enough endpoints to see a significant between-group difference when the researchers designed the study.

For the entire 3 years of follow-up, influenza vaccination was tied to a nonsignificant 7% relative risk reduction for the first primary endpoint, and a nonsignificant 9% relative risk reduction for the second primary endpoint, he reported.

But Dr. Loeb lobbied for the relevance of several significant secondary endpoints that collectively showed a compelling pattern of benefit during his talk. These included, for the full 3-years of follow-up, important, significant reductions relative to placebo of 16% for first all-cause hospitalizations (P = .01), and a 42% relative risk reduction in first cases of pneumonia (P = .0006).

Then there were the benefits that appeared during influenza season. In that analysis, first events for the first primary endpoint fell after vaccination by a significant 18% relative to placebo. The in-season analysis also showed the significant cuts in both all-cause and cardiovascular deaths.

Despite the neutral primary endpoints, “if you look at these data as a whole I think they speak to the importance of vaccinating patients with heart failure against influenza,” Dr. Loeb maintained.



‘Totality of evidence supports vaccination’

“I agree that the totality of evidence supports influenza vaccination,” commented Mark H. Drazner, MD, professor and clinical chief of cardiology at the University of Texas Southwestern Medical Center, Dallas, who was designated discussant for the report.

“The message should be to offer influenza vaccine to patients with heart failure,” Dr. Drazner said in an interview. “Previous data on influenza vaccine in patients with heart failure were largely observational. This was a randomized, prospective, placebo-controlled trial. That’s a step forward. Proving efficacy in a randomized trial is important.”

Dr Drazner added that his institution already promotes a “strong mandate” to vaccinate patients with heart failure against influenza.

“The influenza vaccine is a very effective and cost-efficient public health measure. Preventing hospitalizations of patients with heart failure has so many benefits,” commented Craig Beavers, PharmD, vice president of professional services at Baptist Health in Paducah, Ky., and a discussant during the press briefing.

Mitchel L. Zoler/MDedge News

The Influenza Vaccine To Prevent Adverse Vascular Events (IVVE) trial enrolled people with heart failure in New York Heart Association functional class II, III, or IV from any of 10 low- and middle-income countries including China, India, the Philippines, and multiple countries from Africa and the Middle East. They averaged 57 years of age, and slightly more than half were women.

IVVE was sponsored by McMaster University; the only commercial support that IVVE received was a free supply of influenza vaccine from Sanofi Pasteur. Dr. Loeb, Dr. Drazner, and Dr. Beavers had no disclosures.

The new heart failure (HF) guidelines released by three North American societies had a lot of catching up to do given the significant, even paradigm-shifting, additions to available treatment options in the last few years.

The landscape now includes both new and repurposed drug therapies that benefit almost without regard to ejection fraction (EF), and evidence-based urgency to engage patients early on with at least four core medication classes, so-called quadruple therapy.

Catherine Hackett/MDedge News

The guideline document offers a roadmap for navigating those key issues and many others and uses some creative tactics. They include the introduction of generalist-friendly labels for the traditional but obscurely named four stages of HF severity that, it is hoped, will have wider reach and expand the use of effective therapies.

It introduces additional disease-staging terminology that characterizes the syndrome as a continuum:  

• “At risk for HF” for stage A, applied to asymptomatic patients with risk factors such as diabetes or hypertension but no known cardiac changes.
• “Pre-HF” for stage B, which adds cardiac structural changes or elevated natriuretic peptides, still in the absence of symptoms.
• “Symptomatic HF” for stage C, that is, structural disease with current or previous symptoms.
• “Advanced HF” for stage D, characterized by severe debilitating symptoms or repeated hospitalizations even with guideline-directed medical therapy (GDMT).

The new terms should be “easier for primary care physicians as well as nonspecialists” to remember and use effectively “and easier to translate to the patients,” compared with the solely alphabetical staging labels appearing in the guidelines for more than 15 years, Biykem Bozkurt, MD, PhD, Baylor College of Medicine, Houston, said in an interview.

An emphasis on “at risk for HF” and “pre-HF” in the new document may help efforts to expand primary prevention of HF and management of preclinical HF. The guideline, Dr. Bozkurt said, includes specific treatment recommendations for those early stages.

The document also updates and sometimes introduces “recommendations for advanced heart failure, acute heart failure, and comorbidities – specifically for atrial fibrillation, iron deficiency, sleep apnea, coronary artery disease, and valvular heart disease,” Dr. Bozkurt observed, as well as for cardiomyopathy and HF related to pregnancy and cancer chemotherapy. “So, it’s a very comprehensive guideline.”

Dr. Bozkurt is vice chair of the guideline writing committee and helped introduce the guideline at the annual scientific sessions of the American College of Cardiology. The document, developed by the ACC, the American Heart Association, and the Heart Failure Society of America, was published April 1, 2022, in the societies’ flagship journals, Journal of the American College of Cardiology, Circulation, and the Journal of Cardiac Failure, respectively. It replaces the 2013 guideline from the ACC and AHA and the ACC/AHA/HFSA–focused update from 2017.

“We really need to treat early, and then we need to treat appropriately,” Douglas L. Mann, MD, Washington University in St. Louis, said in an interview. Dr. Mann, who was not involved in development of the new guideline, said he is “enthusiastic” about the new staging terminology.

“I think it makes it easier to convey the message that these people do need medicines, will benefit from medicines, and in some cases heart failure can be preventable,” he said. “I’m in favor of anything that simplifies it and makes it more readily interpretable by busy doctors who aren’t specialists.”

With the new staging terminology and in other ways, the guideline seems to appreciate cardiomyopathy as a journey from preclinical to advanced symptomatic stages – the preclinical “at-risk” stage tightening focus on primary prevention – and updated thinking on classification of HF by EF.

For example, there is new consideration of “HF with improved ejection fraction” (HFimpEF), which suggests the patient may be evolving from HF with reduced EF (HFrEF) to HF with EF that is preserved or mildly reduced, or vice versa.

With HFimpEF, which identifies patients previously with an EF of 40% or lower that improves to beyond 40% at follow-up testing, patients should continue on the medications they had been previously taking for HFrEF, Dr. Bozkurt said.

Patients at risk for HF, in stage A by the older terminology, are characterized by one or more significant HF risk factors, such as hypertension, diabetes, or coronary disease, as they have been in prior guidelines. But the new document, Dr. Bozkurt observed, adds genetic cardiomyopathies and exposure to cardiotoxic agents to the list.

Perhaps surprisingly, the guideline also includes elevated natriuretic peptides as an indicator of “at risk for HF,” with implications for screening. The evidence suggests that, “for patients who are at risk for heart failure, natriuretic peptide-based screening, followed by team-based care, can prevent development of left ventricular dysfunction in heart failure,” Dr. Bozkurt said.

Persons at risk for HF realistically encompass a huge swath of the population given the world prevalence of high blood pressure, obesity, and diabetes. Management of stage A, therefore, focuses on established tenets of primary cardiovascular prevention, such as weight and BP control, exercise, and healthy dietary choices.

They may well be eligible for treatment with sodium-glucose transporter 2 (SGLT2) inhibitors, which have been “game changers,” Dr. Mann said. “Now you can give them to diabetics and it’s going to prevent heart failure and [cardiovascular] events. We didn’t have a drug like that before, so I think that places a lot of emphasis on aggressive treatment of diabetes.”

For patients with symptomatic HF, the document touts multidisciplinary care and early initiation of drugs from each of four drug classes. Such quadruple therapy includes an SGLT2 inhibitor along with a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin system (RAS) inhibitor: the “core foundational therapies” for patients with HFrEF, Dr. Bozkurt observed.

Of note, she said, the angiotensin receptor–neprilysin inhibitor sacubitril/valsartan (Entresto, Novartis) is the preferred RAS inhibitor. But “if the ARNI cannot be used, then use ACE inhibitors.” If the patient is intolerant of ACE inhibitors because of cough or angioedema, then the choice should be an angiotensin-receptor blocker.

“We have very effective therapies offering survival and morbidity benefits as well as improvements in quality of life and reverse remodeling,” Dr. Bozkurt observed. “The most important message is that optimization of therapies, including all of these medication classes, saves lives.”

The guideline also includes, for the first time, a series of “value statements” on cost-effectiveness of different therapies that assign a “high-value” rating to MRAs, hydralazine, and isosorbide dinitrate in otherwise optimally treated self-identified African Americans, and device therapy in appropriately selected patients. The statements hold SGLT2 inhibitors in chronic symptomatic HF and cardiac transplantation in advanced GDMT-resistant HF to be of “intermediate” value.

The value statements, Dr. Bozkurt noted, “are included throughout the document when there is evidence; when there is a high-quality cost-effectiveness study published.”

Dr. Bozkurt disclosed receiving honoraria or consulting fees from Amgen, AstraZeneca, Baxter International, Bristol-Myers Squibb, Sanofi-Aventis, scPharmaceuticals, and Vifor Pharma; serving on a data safety monitoring board for LivaNova USA; and holding other relationships with Abbott Laboratories and Relypsa. Dr. Mann disclosed receiving honoraria or consulting fees from MyoKardia, Novartis, and Novo Nordisk.

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

The new heart failure (HF) guidelines released by three North American societies had a lot of catching up to do given the significant, even paradigm-shifting, additions to available treatment options in the last few years.

The landscape now includes both new and repurposed drug therapies that benefit almost without regard to ejection fraction (EF), and evidence-based urgency to engage patients early on with at least four core medication classes, so-called quadruple therapy.

Catherine Hackett/MDedge News

The guideline document offers a roadmap for navigating those key issues and many others and uses some creative tactics. They include the introduction of generalist-friendly labels for the traditional but obscurely named four stages of HF severity that, it is hoped, will have wider reach and expand the use of effective therapies.

It introduces additional disease-staging terminology that characterizes the syndrome as a continuum:  

• “At risk for HF” for stage A, applied to asymptomatic patients with risk factors such as diabetes or hypertension but no known cardiac changes.
• “Pre-HF” for stage B, which adds cardiac structural changes or elevated natriuretic peptides, still in the absence of symptoms.
• “Symptomatic HF” for stage C, that is, structural disease with current or previous symptoms.
• “Advanced HF” for stage D, characterized by severe debilitating symptoms or repeated hospitalizations even with guideline-directed medical therapy (GDMT).

The new terms should be “easier for primary care physicians as well as nonspecialists” to remember and use effectively “and easier to translate to the patients,” compared with the solely alphabetical staging labels appearing in the guidelines for more than 15 years, Biykem Bozkurt, MD, PhD, Baylor College of Medicine, Houston, said in an interview.

An emphasis on “at risk for HF” and “pre-HF” in the new document may help efforts to expand primary prevention of HF and management of preclinical HF. The guideline, Dr. Bozkurt said, includes specific treatment recommendations for those early stages.

The document also updates and sometimes introduces “recommendations for advanced heart failure, acute heart failure, and comorbidities – specifically for atrial fibrillation, iron deficiency, sleep apnea, coronary artery disease, and valvular heart disease,” Dr. Bozkurt observed, as well as for cardiomyopathy and HF related to pregnancy and cancer chemotherapy. “So, it’s a very comprehensive guideline.”

Dr. Bozkurt is vice chair of the guideline writing committee and helped introduce the guideline at the annual scientific sessions of the American College of Cardiology. The document, developed by the ACC, the American Heart Association, and the Heart Failure Society of America, was published April 1, 2022, in the societies’ flagship journals, Journal of the American College of Cardiology, Circulation, and the Journal of Cardiac Failure, respectively. It replaces the 2013 guideline from the ACC and AHA and the ACC/AHA/HFSA–focused update from 2017.

“We really need to treat early, and then we need to treat appropriately,” Douglas L. Mann, MD, Washington University in St. Louis, said in an interview. Dr. Mann, who was not involved in development of the new guideline, said he is “enthusiastic” about the new staging terminology.

“I think it makes it easier to convey the message that these people do need medicines, will benefit from medicines, and in some cases heart failure can be preventable,” he said. “I’m in favor of anything that simplifies it and makes it more readily interpretable by busy doctors who aren’t specialists.”

With the new staging terminology and in other ways, the guideline seems to appreciate cardiomyopathy as a journey from preclinical to advanced symptomatic stages – the preclinical “at-risk” stage tightening focus on primary prevention – and updated thinking on classification of HF by EF.

For example, there is new consideration of “HF with improved ejection fraction” (HFimpEF), which suggests the patient may be evolving from HF with reduced EF (HFrEF) to HF with EF that is preserved or mildly reduced, or vice versa.

With HFimpEF, which identifies patients previously with an EF of 40% or lower that improves to beyond 40% at follow-up testing, patients should continue on the medications they had been previously taking for HFrEF, Dr. Bozkurt said.

Patients at risk for HF, in stage A by the older terminology, are characterized by one or more significant HF risk factors, such as hypertension, diabetes, or coronary disease, as they have been in prior guidelines. But the new document, Dr. Bozkurt observed, adds genetic cardiomyopathies and exposure to cardiotoxic agents to the list.

Perhaps surprisingly, the guideline also includes elevated natriuretic peptides as an indicator of “at risk for HF,” with implications for screening. The evidence suggests that, “for patients who are at risk for heart failure, natriuretic peptide-based screening, followed by team-based care, can prevent development of left ventricular dysfunction in heart failure,” Dr. Bozkurt said.

Persons at risk for HF realistically encompass a huge swath of the population given the world prevalence of high blood pressure, obesity, and diabetes. Management of stage A, therefore, focuses on established tenets of primary cardiovascular prevention, such as weight and BP control, exercise, and healthy dietary choices.

They may well be eligible for treatment with sodium-glucose transporter 2 (SGLT2) inhibitors, which have been “game changers,” Dr. Mann said. “Now you can give them to diabetics and it’s going to prevent heart failure and [cardiovascular] events. We didn’t have a drug like that before, so I think that places a lot of emphasis on aggressive treatment of diabetes.”

For patients with symptomatic HF, the document touts multidisciplinary care and early initiation of drugs from each of four drug classes. Such quadruple therapy includes an SGLT2 inhibitor along with a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin system (RAS) inhibitor: the “core foundational therapies” for patients with HFrEF, Dr. Bozkurt observed.

Of note, she said, the angiotensin receptor–neprilysin inhibitor sacubitril/valsartan (Entresto, Novartis) is the preferred RAS inhibitor. But “if the ARNI cannot be used, then use ACE inhibitors.” If the patient is intolerant of ACE inhibitors because of cough or angioedema, then the choice should be an angiotensin-receptor blocker.

“We have very effective therapies offering survival and morbidity benefits as well as improvements in quality of life and reverse remodeling,” Dr. Bozkurt observed. “The most important message is that optimization of therapies, including all of these medication classes, saves lives.”

The guideline also includes, for the first time, a series of “value statements” on cost-effectiveness of different therapies that assign a “high-value” rating to MRAs, hydralazine, and isosorbide dinitrate in otherwise optimally treated self-identified African Americans, and device therapy in appropriately selected patients. The statements hold SGLT2 inhibitors in chronic symptomatic HF and cardiac transplantation in advanced GDMT-resistant HF to be of “intermediate” value.

The value statements, Dr. Bozkurt noted, “are included throughout the document when there is evidence; when there is a high-quality cost-effectiveness study published.”

Dr. Bozkurt disclosed receiving honoraria or consulting fees from Amgen, AstraZeneca, Baxter International, Bristol-Myers Squibb, Sanofi-Aventis, scPharmaceuticals, and Vifor Pharma; serving on a data safety monitoring board for LivaNova USA; and holding other relationships with Abbott Laboratories and Relypsa. Dr. Mann disclosed receiving honoraria or consulting fees from MyoKardia, Novartis, and Novo Nordisk.

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

The new heart failure (HF) guidelines released by three North American societies had a lot of catching up to do given the significant, even paradigm-shifting, additions to available treatment options in the last few years.

The landscape now includes both new and repurposed drug therapies that benefit almost without regard to ejection fraction (EF), and evidence-based urgency to engage patients early on with at least four core medication classes, so-called quadruple therapy.

Catherine Hackett/MDedge News

The guideline document offers a roadmap for navigating those key issues and many others and uses some creative tactics. They include the introduction of generalist-friendly labels for the traditional but obscurely named four stages of HF severity that, it is hoped, will have wider reach and expand the use of effective therapies.

It introduces additional disease-staging terminology that characterizes the syndrome as a continuum:  

• “At risk for HF” for stage A, applied to asymptomatic patients with risk factors such as diabetes or hypertension but no known cardiac changes.
• “Pre-HF” for stage B, which adds cardiac structural changes or elevated natriuretic peptides, still in the absence of symptoms.
• “Symptomatic HF” for stage C, that is, structural disease with current or previous symptoms.
• “Advanced HF” for stage D, characterized by severe debilitating symptoms or repeated hospitalizations even with guideline-directed medical therapy (GDMT).

The new terms should be “easier for primary care physicians as well as nonspecialists” to remember and use effectively “and easier to translate to the patients,” compared with the solely alphabetical staging labels appearing in the guidelines for more than 15 years, Biykem Bozkurt, MD, PhD, Baylor College of Medicine, Houston, said in an interview.

An emphasis on “at risk for HF” and “pre-HF” in the new document may help efforts to expand primary prevention of HF and management of preclinical HF. The guideline, Dr. Bozkurt said, includes specific treatment recommendations for those early stages.

The document also updates and sometimes introduces “recommendations for advanced heart failure, acute heart failure, and comorbidities – specifically for atrial fibrillation, iron deficiency, sleep apnea, coronary artery disease, and valvular heart disease,” Dr. Bozkurt observed, as well as for cardiomyopathy and HF related to pregnancy and cancer chemotherapy. “So, it’s a very comprehensive guideline.”

Dr. Bozkurt is vice chair of the guideline writing committee and helped introduce the guideline at the annual scientific sessions of the American College of Cardiology. The document, developed by the ACC, the American Heart Association, and the Heart Failure Society of America, was published April 1, 2022, in the societies’ flagship journals, Journal of the American College of Cardiology, Circulation, and the Journal of Cardiac Failure, respectively. It replaces the 2013 guideline from the ACC and AHA and the ACC/AHA/HFSA–focused update from 2017.

“We really need to treat early, and then we need to treat appropriately,” Douglas L. Mann, MD, Washington University in St. Louis, said in an interview. Dr. Mann, who was not involved in development of the new guideline, said he is “enthusiastic” about the new staging terminology.

“I think it makes it easier to convey the message that these people do need medicines, will benefit from medicines, and in some cases heart failure can be preventable,” he said. “I’m in favor of anything that simplifies it and makes it more readily interpretable by busy doctors who aren’t specialists.”

With the new staging terminology and in other ways, the guideline seems to appreciate cardiomyopathy as a journey from preclinical to advanced symptomatic stages – the preclinical “at-risk” stage tightening focus on primary prevention – and updated thinking on classification of HF by EF.

For example, there is new consideration of “HF with improved ejection fraction” (HFimpEF), which suggests the patient may be evolving from HF with reduced EF (HFrEF) to HF with EF that is preserved or mildly reduced, or vice versa.

With HFimpEF, which identifies patients previously with an EF of 40% or lower that improves to beyond 40% at follow-up testing, patients should continue on the medications they had been previously taking for HFrEF, Dr. Bozkurt said.

Patients at risk for HF, in stage A by the older terminology, are characterized by one or more significant HF risk factors, such as hypertension, diabetes, or coronary disease, as they have been in prior guidelines. But the new document, Dr. Bozkurt observed, adds genetic cardiomyopathies and exposure to cardiotoxic agents to the list.

Perhaps surprisingly, the guideline also includes elevated natriuretic peptides as an indicator of “at risk for HF,” with implications for screening. The evidence suggests that, “for patients who are at risk for heart failure, natriuretic peptide-based screening, followed by team-based care, can prevent development of left ventricular dysfunction in heart failure,” Dr. Bozkurt said.

Persons at risk for HF realistically encompass a huge swath of the population given the world prevalence of high blood pressure, obesity, and diabetes. Management of stage A, therefore, focuses on established tenets of primary cardiovascular prevention, such as weight and BP control, exercise, and healthy dietary choices.

They may well be eligible for treatment with sodium-glucose transporter 2 (SGLT2) inhibitors, which have been “game changers,” Dr. Mann said. “Now you can give them to diabetics and it’s going to prevent heart failure and [cardiovascular] events. We didn’t have a drug like that before, so I think that places a lot of emphasis on aggressive treatment of diabetes.”

For patients with symptomatic HF, the document touts multidisciplinary care and early initiation of drugs from each of four drug classes. Such quadruple therapy includes an SGLT2 inhibitor along with a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin system (RAS) inhibitor: the “core foundational therapies” for patients with HFrEF, Dr. Bozkurt observed.

Of note, she said, the angiotensin receptor–neprilysin inhibitor sacubitril/valsartan (Entresto, Novartis) is the preferred RAS inhibitor. But “if the ARNI cannot be used, then use ACE inhibitors.” If the patient is intolerant of ACE inhibitors because of cough or angioedema, then the choice should be an angiotensin-receptor blocker.

“We have very effective therapies offering survival and morbidity benefits as well as improvements in quality of life and reverse remodeling,” Dr. Bozkurt observed. “The most important message is that optimization of therapies, including all of these medication classes, saves lives.”

The guideline also includes, for the first time, a series of “value statements” on cost-effectiveness of different therapies that assign a “high-value” rating to MRAs, hydralazine, and isosorbide dinitrate in otherwise optimally treated self-identified African Americans, and device therapy in appropriately selected patients. The statements hold SGLT2 inhibitors in chronic symptomatic HF and cardiac transplantation in advanced GDMT-resistant HF to be of “intermediate” value.

The value statements, Dr. Bozkurt noted, “are included throughout the document when there is evidence; when there is a high-quality cost-effectiveness study published.”

Dr. Bozkurt disclosed receiving honoraria or consulting fees from Amgen, AstraZeneca, Baxter International, Bristol-Myers Squibb, Sanofi-Aventis, scPharmaceuticals, and Vifor Pharma; serving on a data safety monitoring board for LivaNova USA; and holding other relationships with Abbott Laboratories and Relypsa. Dr. Mann disclosed receiving honoraria or consulting fees from MyoKardia, Novartis, and Novo Nordisk.

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

People who received personalized nutrition education in a series of sessions at their regular grocery store significantly improved adherence to a healthy diet, in a new “first-of-its-kind” study in which scientific researchers partnered with a large supermarket company.

In the SuperWIN study, participants were given individualized advice from supermarket-based dietitians using data on their own buying habits recorded on their supermarket loyalty cards. This was associated with an increased adherence to the DASH (Dietary Approaches to Stop Hypertension) diet, which emphasizes vegetables, fruits and whole grains while limiting foods that are high in saturated fat, sugar, and sodium and has been shown to lower blood pressure and LDL cholesterol.

Catherine Hackett/MDedge News

One group of patients also received additional education about healthy eating and meal planning through online technologies, and this group showed even better adherence to the DASH diet.

The study was presented at the annual scientific sessions of the American College of Cardiology by Dylan Steen, MD, adjunct associate professor of medicine at the University of Cincinnati.

“The SuperWIN study provides evidence for the benefit of delivering healthy-eating interventions at modern supermarkets and retail-based clinics,” Dr. Steen said. “It demonstrates the efficacy of dietary interventions harnessing the physical environment of the supermarket, the retail-based dietitians working within the store, and the purchasing data captured on the store’s loyalty cards.”

The study was conducted in partnership with Kroger, the largest supermarket chain in the United States, which also operates a large chain of pharmacies and health clinics.

Dr. Steen said the study was addressing one of the biggest public health problems – unhealthy eating – with an innovative approach. “We need to think about how we can extend the reach of modern health care systems into communities and better deliver services right where people are; meet them where they live,” he said at an ACC press conference.

Commenting on the study at the press conference, Eileen Handberg, PhD, professor of medicine at University of Florida, Gainesville, and immediate past chair of the ACC Cardiovascular Care Team Council, said: “I am amazingly excited about this. There is so much potential here. We have never really taken advantage of the current explosion in retail-based health care before.”

Dr. Handberg suggested the study had major implications for the primary prevention of cardiovascular disease. “Little kids go shopping with their parents, so you have the ability here to change behavior from children on up if you can change the dynamic of the choices they make in the grocery store.”

In his presentation, Dr. Steen noted that, despite many longstanding guidelines on healthy eating, about 75% of Americans still have a poor-quality diet. This trial was conducted to see if a new approach could improve that situation. “If we change the environment in which we deliver dietary education, we can make a difference.”

The SuperWIN trial was conducted in 13 Kroger stores in Ohio and Kentucky. The study enrolled 267 people with at least one cardiovascular risk factor from a primary care network who regularly shopped at one of the study stores. All participants also had to be willing to follow the DASH diet, which was taught at each educational session in the trial.

All participants received one “enhanced” medical nutrition therapy that was guided by the individual’s own dietary intake analytics.

They were then randomly assigned to one of three arms. The control group received no further education. The strategy 1 group received six additional teaching sessions in the supermarket aisles over a 3-month period. Each session was guided by updated individualized purchasing data provided to the dietitian and the participant. 

The strategy 2 group received the same six additional teaching sessions as strategy 1, but they also had some additional teaching on healthy eating and meal planning from a variety of online shopping tools, and nutrition and health care apps.  

“The supermarket analytics were automatically collected so the dietitians could tell what each person liked to eat, how much of each product they were buying and how much they were spending,” Dr. Steen explained.

COVID hit halfway through the trial, and 20 participants were withdrawn for their own safety as they could no longer visit the stores, but the trial continued with the rest of the participants with enhanced safety precautions. The overall analysis cohort was 247 participants.

The average age of the participants was mid-50s, around 70% were female, and most did not have a history of cardiovascular disease.

Eating habits were assessed by three 24-hour dietary recalls assessed at the start of the study and at 3 and 6 months. The DASH score, which is a measure of adherence to the DASH diet, was calculated from this information. The score can range from 0 to 90, with an increased score showing increased adherence.

In one analysis, the researchers compared the DASH scores from the two intervention groups together with the control group, and in a second analysis they compared the scores in the strategy 2 group with those in the strategy 1 group.

Before the pandemic there was “near 100%” attendance for the six visits over the 3-month study period, which Dr. Steen said he thought was “remarkable.” During the pandemic, attendance came down to around 80%.

Results showed that the DASH score increased in all three groups at 3 months, with stepwise increases corresponding to the intensity of the intervention. DASH scores increased by 5.8 points in the control group, by 8.6 points in the strategy 1 group, and by 12.4 points in the strategy 2 group.

DASH scores significantly differed between the two intervention groups and the control group (P = .02). “This shows that purchasing data–guided in-store tours do increase the efficacy of dietary education,” Dr. Steen said.

The difference in scores between the strategy 1 and strategy 2 groups was also significant (P = .01). “This shows online enhancements increase adherence to the DASH diet even further,” Dr. Steen commented

By 6 months, the scores had dropped off a little but were still increased from baseline: by 4.4 points in the control group, 6.6 points in the strategy 1 group, and 8.4 points in the strategy 2 group. “There was again a stepwise increase as the intervention intensified, but there was no longer a significant difference between the interventions and control,” Dr. Steen noted.

Secondary endpoints included blood pressure and body mass index. Systolic blood pressure decreased slightly in all three groups: by 2.8 mm Hg in the control group, 6.6 mm Hg in the strategy 1 group, and 5.7 mm Hg in the strategy 2 group. Body mass index was reduced by 0.2, 0.4 and 0.8, respectively, but the between-group differences were not significant.

Dr. Steen said this is the first study of its kind to date in which scientific researchers collaborated with a large supermarket chain. He explained they also involved a primary care network so that health care utilization information will be available.

“We can the integrate retail-based health care information with traditional health care information. And we can start to look at downstream health care utilization and cost outcomes as well, which will be important as we start to think how to evolve the health care system,” he commented. “The hope is that we can get more scientists working with more retailers to really drive the evidence to shape the evolution of our health care system.”

Challenges ahead

Dr. Handberg pointed out there would be challenges in reaching the underserved population who do not shop at the major supermarkets. “We need to figure out how to get partnerships across the whole spectrum of grocery stores.”

She also noted that 3 months (the duration of the study intervention) was not much time to change the eating habits of a family. “Interventions may have to be a bit more intensive to get the change in blood pressure and weight that we would want to see.”

Dr Handberg hoped the major grocery store companies will see the opportunities in this approach. “Changing behavior is very complicated, and the key will be how to make people stick with the changes. But grocery stores are smart. They have got us going to their pharmacies, so getting us to see a dietitian is not that much of a stretch.”

Moderator of the ACC late-breaker session at which the study was presented, Pamela Morris, MD, from the Medical University of South Carolina, Charleston, who is also ACC annual scientific session chair, asked whether the approach could be sustained.

“I am thinking back to the barber shop study of blood pressure treatment and to my knowledge those PharmDs are no longer in those barbershops, taking blood pressures, counseling patients, and prescribing antihypertensives. So is Kroger maintaining a long-term commitment to providing this education, or how can this be financed over the long term?” she asked.

Dr. Steen replied that he believed sustainability to be one of the key strengths of this model. “Retail-based health care is exploding in the U.S. The number of retail outlets offering a comprehensive list of services is going up all the time. These programs exist regardless of whether this trial was conducted or not.”

But Dr. Steen stressed that having an evidence base will be critically important.

“Validation is an enormous part of this evolution in retail-based health care – not only to figure out what works but also to engage payors and others in the process of supporting these interventions. I think the sustainability is there – it is sort of baked into the model – but research will be a huge part of cementing this in and helping us to understand what we should do.”

The study was funded by Kroger. Dr. Steen is a consultant for Sanofi and CEO and cofounder of High Enroll.

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

People who received personalized nutrition education in a series of sessions at their regular grocery store significantly improved adherence to a healthy diet, in a new “first-of-its-kind” study in which scientific researchers partnered with a large supermarket company.

In the SuperWIN study, participants were given individualized advice from supermarket-based dietitians using data on their own buying habits recorded on their supermarket loyalty cards. This was associated with an increased adherence to the DASH (Dietary Approaches to Stop Hypertension) diet, which emphasizes vegetables, fruits and whole grains while limiting foods that are high in saturated fat, sugar, and sodium and has been shown to lower blood pressure and LDL cholesterol.

Catherine Hackett/MDedge News

One group of patients also received additional education about healthy eating and meal planning through online technologies, and this group showed even better adherence to the DASH diet.

The study was presented at the annual scientific sessions of the American College of Cardiology by Dylan Steen, MD, adjunct associate professor of medicine at the University of Cincinnati.

“The SuperWIN study provides evidence for the benefit of delivering healthy-eating interventions at modern supermarkets and retail-based clinics,” Dr. Steen said. “It demonstrates the efficacy of dietary interventions harnessing the physical environment of the supermarket, the retail-based dietitians working within the store, and the purchasing data captured on the store’s loyalty cards.”

The study was conducted in partnership with Kroger, the largest supermarket chain in the United States, which also operates a large chain of pharmacies and health clinics.

Dr. Steen said the study was addressing one of the biggest public health problems – unhealthy eating – with an innovative approach. “We need to think about how we can extend the reach of modern health care systems into communities and better deliver services right where people are; meet them where they live,” he said at an ACC press conference.

Commenting on the study at the press conference, Eileen Handberg, PhD, professor of medicine at University of Florida, Gainesville, and immediate past chair of the ACC Cardiovascular Care Team Council, said: “I am amazingly excited about this. There is so much potential here. We have never really taken advantage of the current explosion in retail-based health care before.”

Dr. Handberg suggested the study had major implications for the primary prevention of cardiovascular disease. “Little kids go shopping with their parents, so you have the ability here to change behavior from children on up if you can change the dynamic of the choices they make in the grocery store.”

In his presentation, Dr. Steen noted that, despite many longstanding guidelines on healthy eating, about 75% of Americans still have a poor-quality diet. This trial was conducted to see if a new approach could improve that situation. “If we change the environment in which we deliver dietary education, we can make a difference.”

The SuperWIN trial was conducted in 13 Kroger stores in Ohio and Kentucky. The study enrolled 267 people with at least one cardiovascular risk factor from a primary care network who regularly shopped at one of the study stores. All participants also had to be willing to follow the DASH diet, which was taught at each educational session in the trial.

All participants received one “enhanced” medical nutrition therapy that was guided by the individual’s own dietary intake analytics.

They were then randomly assigned to one of three arms. The control group received no further education. The strategy 1 group received six additional teaching sessions in the supermarket aisles over a 3-month period. Each session was guided by updated individualized purchasing data provided to the dietitian and the participant. 

The strategy 2 group received the same six additional teaching sessions as strategy 1, but they also had some additional teaching on healthy eating and meal planning from a variety of online shopping tools, and nutrition and health care apps.  

“The supermarket analytics were automatically collected so the dietitians could tell what each person liked to eat, how much of each product they were buying and how much they were spending,” Dr. Steen explained.

COVID hit halfway through the trial, and 20 participants were withdrawn for their own safety as they could no longer visit the stores, but the trial continued with the rest of the participants with enhanced safety precautions. The overall analysis cohort was 247 participants.

The average age of the participants was mid-50s, around 70% were female, and most did not have a history of cardiovascular disease.

Eating habits were assessed by three 24-hour dietary recalls assessed at the start of the study and at 3 and 6 months. The DASH score, which is a measure of adherence to the DASH diet, was calculated from this information. The score can range from 0 to 90, with an increased score showing increased adherence.

In one analysis, the researchers compared the DASH scores from the two intervention groups together with the control group, and in a second analysis they compared the scores in the strategy 2 group with those in the strategy 1 group.

Before the pandemic there was “near 100%” attendance for the six visits over the 3-month study period, which Dr. Steen said he thought was “remarkable.” During the pandemic, attendance came down to around 80%.

Results showed that the DASH score increased in all three groups at 3 months, with stepwise increases corresponding to the intensity of the intervention. DASH scores increased by 5.8 points in the control group, by 8.6 points in the strategy 1 group, and by 12.4 points in the strategy 2 group.

DASH scores significantly differed between the two intervention groups and the control group (P = .02). “This shows that purchasing data–guided in-store tours do increase the efficacy of dietary education,” Dr. Steen said.

The difference in scores between the strategy 1 and strategy 2 groups was also significant (P = .01). “This shows online enhancements increase adherence to the DASH diet even further,” Dr. Steen commented

By 6 months, the scores had dropped off a little but were still increased from baseline: by 4.4 points in the control group, 6.6 points in the strategy 1 group, and 8.4 points in the strategy 2 group. “There was again a stepwise increase as the intervention intensified, but there was no longer a significant difference between the interventions and control,” Dr. Steen noted.

Secondary endpoints included blood pressure and body mass index. Systolic blood pressure decreased slightly in all three groups: by 2.8 mm Hg in the control group, 6.6 mm Hg in the strategy 1 group, and 5.7 mm Hg in the strategy 2 group. Body mass index was reduced by 0.2, 0.4 and 0.8, respectively, but the between-group differences were not significant.

Dr. Steen said this is the first study of its kind to date in which scientific researchers collaborated with a large supermarket chain. He explained they also involved a primary care network so that health care utilization information will be available.

“We can the integrate retail-based health care information with traditional health care information. And we can start to look at downstream health care utilization and cost outcomes as well, which will be important as we start to think how to evolve the health care system,” he commented. “The hope is that we can get more scientists working with more retailers to really drive the evidence to shape the evolution of our health care system.”

Challenges ahead

Dr. Handberg pointed out there would be challenges in reaching the underserved population who do not shop at the major supermarkets. “We need to figure out how to get partnerships across the whole spectrum of grocery stores.”

She also noted that 3 months (the duration of the study intervention) was not much time to change the eating habits of a family. “Interventions may have to be a bit more intensive to get the change in blood pressure and weight that we would want to see.”

Dr Handberg hoped the major grocery store companies will see the opportunities in this approach. “Changing behavior is very complicated, and the key will be how to make people stick with the changes. But grocery stores are smart. They have got us going to their pharmacies, so getting us to see a dietitian is not that much of a stretch.”

Moderator of the ACC late-breaker session at which the study was presented, Pamela Morris, MD, from the Medical University of South Carolina, Charleston, who is also ACC annual scientific session chair, asked whether the approach could be sustained.

“I am thinking back to the barber shop study of blood pressure treatment and to my knowledge those PharmDs are no longer in those barbershops, taking blood pressures, counseling patients, and prescribing antihypertensives. So is Kroger maintaining a long-term commitment to providing this education, or how can this be financed over the long term?” she asked.

Dr. Steen replied that he believed sustainability to be one of the key strengths of this model. “Retail-based health care is exploding in the U.S. The number of retail outlets offering a comprehensive list of services is going up all the time. These programs exist regardless of whether this trial was conducted or not.”

But Dr. Steen stressed that having an evidence base will be critically important.

“Validation is an enormous part of this evolution in retail-based health care – not only to figure out what works but also to engage payors and others in the process of supporting these interventions. I think the sustainability is there – it is sort of baked into the model – but research will be a huge part of cementing this in and helping us to understand what we should do.”

The study was funded by Kroger. Dr. Steen is a consultant for Sanofi and CEO and cofounder of High Enroll.

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

People who received personalized nutrition education in a series of sessions at their regular grocery store significantly improved adherence to a healthy diet, in a new “first-of-its-kind” study in which scientific researchers partnered with a large supermarket company.

In the SuperWIN study, participants were given individualized advice from supermarket-based dietitians using data on their own buying habits recorded on their supermarket loyalty cards. This was associated with an increased adherence to the DASH (Dietary Approaches to Stop Hypertension) diet, which emphasizes vegetables, fruits and whole grains while limiting foods that are high in saturated fat, sugar, and sodium and has been shown to lower blood pressure and LDL cholesterol.

Catherine Hackett/MDedge News

One group of patients also received additional education about healthy eating and meal planning through online technologies, and this group showed even better adherence to the DASH diet.

The study was presented at the annual scientific sessions of the American College of Cardiology by Dylan Steen, MD, adjunct associate professor of medicine at the University of Cincinnati.

“The SuperWIN study provides evidence for the benefit of delivering healthy-eating interventions at modern supermarkets and retail-based clinics,” Dr. Steen said. “It demonstrates the efficacy of dietary interventions harnessing the physical environment of the supermarket, the retail-based dietitians working within the store, and the purchasing data captured on the store’s loyalty cards.”

The study was conducted in partnership with Kroger, the largest supermarket chain in the United States, which also operates a large chain of pharmacies and health clinics.

Dr. Steen said the study was addressing one of the biggest public health problems – unhealthy eating – with an innovative approach. “We need to think about how we can extend the reach of modern health care systems into communities and better deliver services right where people are; meet them where they live,” he said at an ACC press conference.

Commenting on the study at the press conference, Eileen Handberg, PhD, professor of medicine at University of Florida, Gainesville, and immediate past chair of the ACC Cardiovascular Care Team Council, said: “I am amazingly excited about this. There is so much potential here. We have never really taken advantage of the current explosion in retail-based health care before.”

Dr. Handberg suggested the study had major implications for the primary prevention of cardiovascular disease. “Little kids go shopping with their parents, so you have the ability here to change behavior from children on up if you can change the dynamic of the choices they make in the grocery store.”

In his presentation, Dr. Steen noted that, despite many longstanding guidelines on healthy eating, about 75% of Americans still have a poor-quality diet. This trial was conducted to see if a new approach could improve that situation. “If we change the environment in which we deliver dietary education, we can make a difference.”

The SuperWIN trial was conducted in 13 Kroger stores in Ohio and Kentucky. The study enrolled 267 people with at least one cardiovascular risk factor from a primary care network who regularly shopped at one of the study stores. All participants also had to be willing to follow the DASH diet, which was taught at each educational session in the trial.

All participants received one “enhanced” medical nutrition therapy that was guided by the individual’s own dietary intake analytics.

They were then randomly assigned to one of three arms. The control group received no further education. The strategy 1 group received six additional teaching sessions in the supermarket aisles over a 3-month period. Each session was guided by updated individualized purchasing data provided to the dietitian and the participant. 

The strategy 2 group received the same six additional teaching sessions as strategy 1, but they also had some additional teaching on healthy eating and meal planning from a variety of online shopping tools, and nutrition and health care apps.  

“The supermarket analytics were automatically collected so the dietitians could tell what each person liked to eat, how much of each product they were buying and how much they were spending,” Dr. Steen explained.

COVID hit halfway through the trial, and 20 participants were withdrawn for their own safety as they could no longer visit the stores, but the trial continued with the rest of the participants with enhanced safety precautions. The overall analysis cohort was 247 participants.

The average age of the participants was mid-50s, around 70% were female, and most did not have a history of cardiovascular disease.

Eating habits were assessed by three 24-hour dietary recalls assessed at the start of the study and at 3 and 6 months. The DASH score, which is a measure of adherence to the DASH diet, was calculated from this information. The score can range from 0 to 90, with an increased score showing increased adherence.

In one analysis, the researchers compared the DASH scores from the two intervention groups together with the control group, and in a second analysis they compared the scores in the strategy 2 group with those in the strategy 1 group.

Before the pandemic there was “near 100%” attendance for the six visits over the 3-month study period, which Dr. Steen said he thought was “remarkable.” During the pandemic, attendance came down to around 80%.

Results showed that the DASH score increased in all three groups at 3 months, with stepwise increases corresponding to the intensity of the intervention. DASH scores increased by 5.8 points in the control group, by 8.6 points in the strategy 1 group, and by 12.4 points in the strategy 2 group.

DASH scores significantly differed between the two intervention groups and the control group (P = .02). “This shows that purchasing data–guided in-store tours do increase the efficacy of dietary education,” Dr. Steen said.

The difference in scores between the strategy 1 and strategy 2 groups was also significant (P = .01). “This shows online enhancements increase adherence to the DASH diet even further,” Dr. Steen commented

By 6 months, the scores had dropped off a little but were still increased from baseline: by 4.4 points in the control group, 6.6 points in the strategy 1 group, and 8.4 points in the strategy 2 group. “There was again a stepwise increase as the intervention intensified, but there was no longer a significant difference between the interventions and control,” Dr. Steen noted.

Secondary endpoints included blood pressure and body mass index. Systolic blood pressure decreased slightly in all three groups: by 2.8 mm Hg in the control group, 6.6 mm Hg in the strategy 1 group, and 5.7 mm Hg in the strategy 2 group. Body mass index was reduced by 0.2, 0.4 and 0.8, respectively, but the between-group differences were not significant.

Dr. Steen said this is the first study of its kind to date in which scientific researchers collaborated with a large supermarket chain. He explained they also involved a primary care network so that health care utilization information will be available.

“We can the integrate retail-based health care information with traditional health care information. And we can start to look at downstream health care utilization and cost outcomes as well, which will be important as we start to think how to evolve the health care system,” he commented. “The hope is that we can get more scientists working with more retailers to really drive the evidence to shape the evolution of our health care system.”

Challenges ahead

Dr. Handberg pointed out there would be challenges in reaching the underserved population who do not shop at the major supermarkets. “We need to figure out how to get partnerships across the whole spectrum of grocery stores.”

She also noted that 3 months (the duration of the study intervention) was not much time to change the eating habits of a family. “Interventions may have to be a bit more intensive to get the change in blood pressure and weight that we would want to see.”

Dr Handberg hoped the major grocery store companies will see the opportunities in this approach. “Changing behavior is very complicated, and the key will be how to make people stick with the changes. But grocery stores are smart. They have got us going to their pharmacies, so getting us to see a dietitian is not that much of a stretch.”

Moderator of the ACC late-breaker session at which the study was presented, Pamela Morris, MD, from the Medical University of South Carolina, Charleston, who is also ACC annual scientific session chair, asked whether the approach could be sustained.

“I am thinking back to the barber shop study of blood pressure treatment and to my knowledge those PharmDs are no longer in those barbershops, taking blood pressures, counseling patients, and prescribing antihypertensives. So is Kroger maintaining a long-term commitment to providing this education, or how can this be financed over the long term?” she asked.

Dr. Steen replied that he believed sustainability to be one of the key strengths of this model. “Retail-based health care is exploding in the U.S. The number of retail outlets offering a comprehensive list of services is going up all the time. These programs exist regardless of whether this trial was conducted or not.”

But Dr. Steen stressed that having an evidence base will be critically important.

“Validation is an enormous part of this evolution in retail-based health care – not only to figure out what works but also to engage payors and others in the process of supporting these interventions. I think the sustainability is there – it is sort of baked into the model – but research will be a huge part of cementing this in and helping us to understand what we should do.”

The study was funded by Kroger. Dr. Steen is a consultant for Sanofi and CEO and cofounder of High Enroll.

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

In a randomized trial of patients with angina and no obstructive coronary artery disease (ANOCA), 6 weeks of treatment with diltiazem did not improve coronary vasomotor dysfunction – apart from epicardial spasm – or angina symptoms and quality of life. 

The trial investigated whether this therapy would improve these outcomes in patients with two mutually exclusive subgroups, or endotypes, of coronary vasomotor dysfunction: coronary artery spasm (epicardial spasm, microvascular spasm) or coronary microvascular dysfunction indicated by coronary flow reserve (CFR) and index of microvascular resistance (IMR) values.

Treatment success, the primary study endpoint – defined as normalization of one of the abnormal endotypes and no normal endotype becoming abnormal – was similar after treatment with diltiazem, compared with placebo. Nor were there significant differences for secondary endpoints apart from improvements in epicardial spasm in the two groups.

Tijn Jansen, MD, presented these findings from the EDIT-CMD trial in a featured clinical research session at the annual scientific sessions of the American College of Cardiology. The study was simultaneously published online April 2, 2022, in JACC: Cardiovascular Imaging.

“This first study using repeated coronary function testing provides a platform for future research,” concluded Dr. Jansen, a PhD candidate in the department of cardiology, Radboud University, Nijmegen, the Netherlands.

“We were surprised indeed” that diltiazem did not meet its primary endpoint for successful treatment and did not reduce symptoms or improve quality of life, compared with placebo, unlike results of the CorMicA trial, he said in an interview.

“We did find a treatment success, however, of 21%, which was slightly lower than expected, but it was not better than just giving placebo. This was similar regarding symptoms and quality of life, where we did find an overall improvement with diltiazem, but again not higher than using placebo,” he added. “It seems that giving the diagnosis to these patients itself creates a reduction in symptoms,” that might be caused by a reduction in stress, Dr. Jansen suggested.

The clinical implication, he said, is that more randomized controlled trials in this patient population are needed to permit evidence-based patient-tailored treatment, based on the different endotypes. “It might even be imaginable to test effectiveness in each individual patient using coronary function testing,” he said.

These tests are more and more commonly used in clinical practice, Dr. Jansen noted. “In the Netherlands, we recently launched the NL-CFT registry, which enables the participating centers to perform the CFT with a standardized protocol, with the goal to collect data and increase knowledge in this patient population.”

Heterogeneous population?

“I think probably the reason this trial was negative is [that coronary vasomotor dysfunction is] just too heterogeneous,” assigned discussant, C. Noel Bairey Merz, MD, commented.

First RCT of diltiazem in patients with ANOCA

Up to 40% of patients undergoing coronary angiography for stable angina do not have obstructive coronary artery disease (CAD), and 60%-90% of these patients have coronary vasomotor dysfunction, Dr. Jansen noted.

The landmark CorMicA trial showed that diagnosing the specific endotype of coronary vasomotor dysfunction using coronary function testing allows for tailored medication that decreased angina and improved quality of life, the researchers noted.

A recent European Society of Cardiology position paper on ANOCA “recommends the use of various pharmacological treatments including calcium-channel blockers, beta-blockers, ACE inhibitors, statins, and nitric oxide modulators, of which CCBs have the most prominent role in both endotypes of coronary vasospasms” and coronary microvascular dysfunction, they wrote.

“However, evidence substantiating these recommendations is lacking,” the researchers added, “since it is based on studies in a different population, with small sample sizes, or not placebo controlled.”

To investigate this, between 2019 and 2021, EDIT-CMD enrolled 126 adults aged 18 years and older who had two or more chronic angina episodes per week and no signs of obstructive CAD, who were seen at three hospitals specializing in ANOCA in the Netherlands.

The participants underwent coronary function testing that consisted of an acetylcholine spasm provocation test to evaluate for epicardial spasm and microvascular spasm, and a bolus thermodilution test with adenosine, to assess CFR and IMR. Coronary microvascular dysfunction was defined as CFR less than 2.0 and IMR of 25 or greater.

Of 99 patients with vasospasm or microvascular dysfunction, 85 patients were randomly assigned to receive diltiazem (n = 41) or placebo (n = 44) for 6 weeks.

The patients in both groups had a mean age of 58 years, and 29% were male; 22% had previously undergone percutaneous coronary intervention, and 48% had severe angina (Canadian Cardiovascular Society grade III/IV).

At baseline, about 50% had epicardial spasm, 25% had microvascular spasm and 25% had no spasm, and 54% in the diltiazem group and 73% in the placebo group had microvascular dysfunction.

After 6 weeks, 73 patients (35 in the placebo group and 38 in the diltiazem group) were available for repeat coronary function testing.

For the primary outcome, after 6 weeks of treatment, the proportion of patients with normalization of one abnormal parameter of coronary vasomotor dysfunction, without any normal parameter becoming abnormal, occurred in 8 patients (21%) in the diltiazem group versus 10 patients (29%) in the placebo group (P = .46)

In secondary outcomes, after 6 weeks of treatment, there were no significant differences in the prevalence of microvascular dysfunction, in Seattle Angina Questionnaire scores for angina symptoms, or RAND-36 scores for quality of life between patients who received diltiazem vs those who received placebo.

However, more patients in the diltiazem group than in the placebo group progressed from epicardial spasm to microvascular or no spasm (47% vs. 6%; P = .006).

The EDIT-CMD trial was sponsored by Abbott. Dr. Jansen has no relevant financial disclosures. Dr. Bairey Merz discloses having a fiduciary role and shares in iRhythm and being on the advisory board for Sanofi.

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

In a randomized trial of patients with angina and no obstructive coronary artery disease (ANOCA), 6 weeks of treatment with diltiazem did not improve coronary vasomotor dysfunction – apart from epicardial spasm – or angina symptoms and quality of life. 

The trial investigated whether this therapy would improve these outcomes in patients with two mutually exclusive subgroups, or endotypes, of coronary vasomotor dysfunction: coronary artery spasm (epicardial spasm, microvascular spasm) or coronary microvascular dysfunction indicated by coronary flow reserve (CFR) and index of microvascular resistance (IMR) values.

Treatment success, the primary study endpoint – defined as normalization of one of the abnormal endotypes and no normal endotype becoming abnormal – was similar after treatment with diltiazem, compared with placebo. Nor were there significant differences for secondary endpoints apart from improvements in epicardial spasm in the two groups.

Tijn Jansen, MD, presented these findings from the EDIT-CMD trial in a featured clinical research session at the annual scientific sessions of the American College of Cardiology. The study was simultaneously published online April 2, 2022, in JACC: Cardiovascular Imaging.

“This first study using repeated coronary function testing provides a platform for future research,” concluded Dr. Jansen, a PhD candidate in the department of cardiology, Radboud University, Nijmegen, the Netherlands.

“We were surprised indeed” that diltiazem did not meet its primary endpoint for successful treatment and did not reduce symptoms or improve quality of life, compared with placebo, unlike results of the CorMicA trial, he said in an interview.

“We did find a treatment success, however, of 21%, which was slightly lower than expected, but it was not better than just giving placebo. This was similar regarding symptoms and quality of life, where we did find an overall improvement with diltiazem, but again not higher than using placebo,” he added. “It seems that giving the diagnosis to these patients itself creates a reduction in symptoms,” that might be caused by a reduction in stress, Dr. Jansen suggested.

The clinical implication, he said, is that more randomized controlled trials in this patient population are needed to permit evidence-based patient-tailored treatment, based on the different endotypes. “It might even be imaginable to test effectiveness in each individual patient using coronary function testing,” he said.

These tests are more and more commonly used in clinical practice, Dr. Jansen noted. “In the Netherlands, we recently launched the NL-CFT registry, which enables the participating centers to perform the CFT with a standardized protocol, with the goal to collect data and increase knowledge in this patient population.”

Heterogeneous population?

“I think probably the reason this trial was negative is [that coronary vasomotor dysfunction is] just too heterogeneous,” assigned discussant, C. Noel Bairey Merz, MD, commented.

First RCT of diltiazem in patients with ANOCA

Up to 40% of patients undergoing coronary angiography for stable angina do not have obstructive coronary artery disease (CAD), and 60%-90% of these patients have coronary vasomotor dysfunction, Dr. Jansen noted.

The landmark CorMicA trial showed that diagnosing the specific endotype of coronary vasomotor dysfunction using coronary function testing allows for tailored medication that decreased angina and improved quality of life, the researchers noted.

A recent European Society of Cardiology position paper on ANOCA “recommends the use of various pharmacological treatments including calcium-channel blockers, beta-blockers, ACE inhibitors, statins, and nitric oxide modulators, of which CCBs have the most prominent role in both endotypes of coronary vasospasms” and coronary microvascular dysfunction, they wrote.

“However, evidence substantiating these recommendations is lacking,” the researchers added, “since it is based on studies in a different population, with small sample sizes, or not placebo controlled.”

To investigate this, between 2019 and 2021, EDIT-CMD enrolled 126 adults aged 18 years and older who had two or more chronic angina episodes per week and no signs of obstructive CAD, who were seen at three hospitals specializing in ANOCA in the Netherlands.

The participants underwent coronary function testing that consisted of an acetylcholine spasm provocation test to evaluate for epicardial spasm and microvascular spasm, and a bolus thermodilution test with adenosine, to assess CFR and IMR. Coronary microvascular dysfunction was defined as CFR less than 2.0 and IMR of 25 or greater.

Of 99 patients with vasospasm or microvascular dysfunction, 85 patients were randomly assigned to receive diltiazem (n = 41) or placebo (n = 44) for 6 weeks.

The patients in both groups had a mean age of 58 years, and 29% were male; 22% had previously undergone percutaneous coronary intervention, and 48% had severe angina (Canadian Cardiovascular Society grade III/IV).

At baseline, about 50% had epicardial spasm, 25% had microvascular spasm and 25% had no spasm, and 54% in the diltiazem group and 73% in the placebo group had microvascular dysfunction.

After 6 weeks, 73 patients (35 in the placebo group and 38 in the diltiazem group) were available for repeat coronary function testing.

For the primary outcome, after 6 weeks of treatment, the proportion of patients with normalization of one abnormal parameter of coronary vasomotor dysfunction, without any normal parameter becoming abnormal, occurred in 8 patients (21%) in the diltiazem group versus 10 patients (29%) in the placebo group (P = .46)

In secondary outcomes, after 6 weeks of treatment, there were no significant differences in the prevalence of microvascular dysfunction, in Seattle Angina Questionnaire scores for angina symptoms, or RAND-36 scores for quality of life between patients who received diltiazem vs those who received placebo.

However, more patients in the diltiazem group than in the placebo group progressed from epicardial spasm to microvascular or no spasm (47% vs. 6%; P = .006).

The EDIT-CMD trial was sponsored by Abbott. Dr. Jansen has no relevant financial disclosures. Dr. Bairey Merz discloses having a fiduciary role and shares in iRhythm and being on the advisory board for Sanofi.

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

In a randomized trial of patients with angina and no obstructive coronary artery disease (ANOCA), 6 weeks of treatment with diltiazem did not improve coronary vasomotor dysfunction – apart from epicardial spasm – or angina symptoms and quality of life. 

The trial investigated whether this therapy would improve these outcomes in patients with two mutually exclusive subgroups, or endotypes, of coronary vasomotor dysfunction: coronary artery spasm (epicardial spasm, microvascular spasm) or coronary microvascular dysfunction indicated by coronary flow reserve (CFR) and index of microvascular resistance (IMR) values.

Treatment success, the primary study endpoint – defined as normalization of one of the abnormal endotypes and no normal endotype becoming abnormal – was similar after treatment with diltiazem, compared with placebo. Nor were there significant differences for secondary endpoints apart from improvements in epicardial spasm in the two groups.

Tijn Jansen, MD, presented these findings from the EDIT-CMD trial in a featured clinical research session at the annual scientific sessions of the American College of Cardiology. The study was simultaneously published online April 2, 2022, in JACC: Cardiovascular Imaging.

“This first study using repeated coronary function testing provides a platform for future research,” concluded Dr. Jansen, a PhD candidate in the department of cardiology, Radboud University, Nijmegen, the Netherlands.

“We were surprised indeed” that diltiazem did not meet its primary endpoint for successful treatment and did not reduce symptoms or improve quality of life, compared with placebo, unlike results of the CorMicA trial, he said in an interview.

“We did find a treatment success, however, of 21%, which was slightly lower than expected, but it was not better than just giving placebo. This was similar regarding symptoms and quality of life, where we did find an overall improvement with diltiazem, but again not higher than using placebo,” he added. “It seems that giving the diagnosis to these patients itself creates a reduction in symptoms,” that might be caused by a reduction in stress, Dr. Jansen suggested.

The clinical implication, he said, is that more randomized controlled trials in this patient population are needed to permit evidence-based patient-tailored treatment, based on the different endotypes. “It might even be imaginable to test effectiveness in each individual patient using coronary function testing,” he said.

These tests are more and more commonly used in clinical practice, Dr. Jansen noted. “In the Netherlands, we recently launched the NL-CFT registry, which enables the participating centers to perform the CFT with a standardized protocol, with the goal to collect data and increase knowledge in this patient population.”

Heterogeneous population?

“I think probably the reason this trial was negative is [that coronary vasomotor dysfunction is] just too heterogeneous,” assigned discussant, C. Noel Bairey Merz, MD, commented.

First RCT of diltiazem in patients with ANOCA

Up to 40% of patients undergoing coronary angiography for stable angina do not have obstructive coronary artery disease (CAD), and 60%-90% of these patients have coronary vasomotor dysfunction, Dr. Jansen noted.

The landmark CorMicA trial showed that diagnosing the specific endotype of coronary vasomotor dysfunction using coronary function testing allows for tailored medication that decreased angina and improved quality of life, the researchers noted.

A recent European Society of Cardiology position paper on ANOCA “recommends the use of various pharmacological treatments including calcium-channel blockers, beta-blockers, ACE inhibitors, statins, and nitric oxide modulators, of which CCBs have the most prominent role in both endotypes of coronary vasospasms” and coronary microvascular dysfunction, they wrote.

“However, evidence substantiating these recommendations is lacking,” the researchers added, “since it is based on studies in a different population, with small sample sizes, or not placebo controlled.”

To investigate this, between 2019 and 2021, EDIT-CMD enrolled 126 adults aged 18 years and older who had two or more chronic angina episodes per week and no signs of obstructive CAD, who were seen at three hospitals specializing in ANOCA in the Netherlands.

The participants underwent coronary function testing that consisted of an acetylcholine spasm provocation test to evaluate for epicardial spasm and microvascular spasm, and a bolus thermodilution test with adenosine, to assess CFR and IMR. Coronary microvascular dysfunction was defined as CFR less than 2.0 and IMR of 25 or greater.

Of 99 patients with vasospasm or microvascular dysfunction, 85 patients were randomly assigned to receive diltiazem (n = 41) or placebo (n = 44) for 6 weeks.

The patients in both groups had a mean age of 58 years, and 29% were male; 22% had previously undergone percutaneous coronary intervention, and 48% had severe angina (Canadian Cardiovascular Society grade III/IV).

At baseline, about 50% had epicardial spasm, 25% had microvascular spasm and 25% had no spasm, and 54% in the diltiazem group and 73% in the placebo group had microvascular dysfunction.

After 6 weeks, 73 patients (35 in the placebo group and 38 in the diltiazem group) were available for repeat coronary function testing.

For the primary outcome, after 6 weeks of treatment, the proportion of patients with normalization of one abnormal parameter of coronary vasomotor dysfunction, without any normal parameter becoming abnormal, occurred in 8 patients (21%) in the diltiazem group versus 10 patients (29%) in the placebo group (P = .46)

In secondary outcomes, after 6 weeks of treatment, there were no significant differences in the prevalence of microvascular dysfunction, in Seattle Angina Questionnaire scores for angina symptoms, or RAND-36 scores for quality of life between patients who received diltiazem vs those who received placebo.

However, more patients in the diltiazem group than in the placebo group progressed from epicardial spasm to microvascular or no spasm (47% vs. 6%; P = .006).

The EDIT-CMD trial was sponsored by Abbott. Dr. Jansen has no relevant financial disclosures. Dr. Bairey Merz discloses having a fiduciary role and shares in iRhythm and being on the advisory board for Sanofi.

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

Pregnant women with even mild hypertension should receive blood pressure–lowering medications to reduce the likelihood of adverse outcomes for the mother and the child, according to a large, open-label, randomized trial.

“Treating to the blood pressure goal in this study reduced the risk of adverse events associated with pregnancy but did not impair fetal growth,” Alan T. Tita, MD, PhD, associate dean for Global and Women’s Health, University of Alabama, Birmingham, reported at the annual scientific sessions of the American College of Cardiology.

The question of whether to treat chronic hypertension during pregnancy has been “an international controversy for decades,” said Dr. Tita, who led the investigator-initiated Chronic Hypertension and Pregnancy (CHAP) trial.

For the composite primary outcome of severe preeclampsia, medically indicated preterm birth at less than 35 weeks of gestation, placental abruption, or fetal/neonatal death, the treatment of hypertension versus no treatment showed a relative risk reduction of 18% (30.2% vs. 37%, (hazard ratio, 0.82; P < .001).
 

Small for gestational age is primary safety endpoint

An increase in preeclampsia risk in women whose fetus was small for gestational age (SGA), a theoretical consequence of reductions in arterial pressure, was not seen. The rate of SGA, defined as below the 10^th percentile, was slightly higher in the treatment group (11.2% vs. 10.4%), but the difference did not approach significance (P = 0.76).

By answering this long-pending question, the CHAP data are “practice changing,” declared an ACC-invited commentator, Athena Poppas, MD, chief of cardiology and director of the Lifespan Cardiovascular Institute, Providence, R.I. She agreed that the need for treatment of mild chronic hypertension has been a dilemma for clinicians that is now acceptably resolved.

In this trial, 2,408 pregnant women with chronic mild hypertension defined as a blood pressure of 160/90 mm Hg were randomized to treatment with a goal blood pressure of less than 140/90 mm Hg or no treatment unless the blood pressure rose to at least 160/105. All women had singleton pregnancies. Enrollment before 23 weeks of gestation was required. Severe hypertension (at least 160/105 mm Hg) was an exclusion criterion, as were several comorbidities, such as kidney disease.
 

Combination therapy accepted for <140/90 mm Hg goal

The beta-blocker labetalol or the calcium channel blocker nifedipine as single agents were the preferred antihypertensive medications in the protocol, but other medications were permitted. To reach the blood pressure goal, the single-agent therapy was titrated to the maximum dose before starting a second agent.

After randomization the systolic and diastolic blood pressures fell in both groups, but they fell more and remained consistently lower in the active treatment group, particularly during the first 20 weeks after randomization, according to graphs displayed by Dr. Tita. Over the course of the study, the mean diastolic blood pressures were 129.5 and 132.6 mm Hg in the active treatment and control groups, respectively, while the systolic pressures were 79.1 vs. 81.5 mm Hg.

When the components of the primary outcome were evaluated separately, the greatest advantage of treatment was the reduction in the rate of severe eclampsia (23.3% vs. 29.1%; HR, 0.80: 95% confidence interval, 0.70-0.92) and preterm birth (12.2% vs. 16.7%; HR, 0.73: 95% CI, 0.60-0.89).

Across a large array of subgroups, including those with or without diabetes and those treated before or after 14 weeks of gestation, there was a consistent advantage for treatment, even if not statistically different. It is notable that 48% of patients were Black and 35% had a body mass index of at least 40. The active treatment was favored across all groups stratified by these characteristics.

Although the incidences of placental abruption (1.7% on treatment vs. 1.9% without) and fetal or neonatal death (3.5% vs. 4.3%) were lower in the active treatment group, they were uncommon events in both arms of the study. The differences did not reach statistical significance.
 

Maternal morbidity rates lower on treatment

Severe SGA, which was defined as below the 5^th percentile, was also numerically but not significantly higher in the control arm than in the group receiving treatment (5.1% vs. 5.5%), but the incidence of composite adverse maternal events was numerically lower (2.1% vs. 2.8%). The incidences of all components of maternal morbidity, such as maternal death (0.1% vs. 0.2%) pulmonary edema (0.4% vs. 0.9%), heart failure (0.1% vs. 0.1%), and acute kidney injury (0.8% vs. 1.2%), were either lower or the same on active treatment versus no treatment.

According to Dr. Tita, who called CHAP one of the largest and most diverse studies to address the value of treating mild hypertension in pregnancy, the American College of Obstetricians and Gynecologists (ACOG) is evaluating these data for changing their current guidelines for managing hypertension during pregnancy.

“The rate of chronic hypertension during pregnancy has been rising in the United States due to the increase in the average age of pregnant women and the rising rates of obesity,” Dr. Tita commented.

“We definitely needed these data,” said Mary Norine Walsh, MD, medical director, Ascension Saint Vincent Cardiovascular Research Institute, Indianapolis. Not only has the value of treating mild hypertension been unresolved, but Dr. Walsh pointed out that the rates of maternal mortality in the United States are rising and now generally exceed those of many other developed countries.

There are several features in the design of this trial that make the results even more salient to clinical practice, according to Dr. Walsh. This includes the fact that about half of patients enrolled were on Medicaid. As a result, the study confirmed benefit in what Dr. Walsh characterized as a “vulnerable” population.

“We will be busy now to make sure that our [pregnant] patients are achieving these target blood pressures,” Dr. Walsh said. She indicated that CHAP validates the treatment target of 140/90 mm Hg as a standard of care.

The results were published in the New England Journal of Medicine simultaneously with its ACC presentation.

The trial was funded by the National Heart, Lung, and Blood Institute. Dr. Tita reports research grants from Pfizer. Dr. Walsh reports a financial relationship with EBR Systems. Dr. Poppas reports no potential conflicts of interest.

Pregnant women with even mild hypertension should receive blood pressure–lowering medications to reduce the likelihood of adverse outcomes for the mother and the child, according to a large, open-label, randomized trial.

“Treating to the blood pressure goal in this study reduced the risk of adverse events associated with pregnancy but did not impair fetal growth,” Alan T. Tita, MD, PhD, associate dean for Global and Women’s Health, University of Alabama, Birmingham, reported at the annual scientific sessions of the American College of Cardiology.

The question of whether to treat chronic hypertension during pregnancy has been “an international controversy for decades,” said Dr. Tita, who led the investigator-initiated Chronic Hypertension and Pregnancy (CHAP) trial.

For the composite primary outcome of severe preeclampsia, medically indicated preterm birth at less than 35 weeks of gestation, placental abruption, or fetal/neonatal death, the treatment of hypertension versus no treatment showed a relative risk reduction of 18% (30.2% vs. 37%, (hazard ratio, 0.82; P < .001).
 

Small for gestational age is primary safety endpoint

An increase in preeclampsia risk in women whose fetus was small for gestational age (SGA), a theoretical consequence of reductions in arterial pressure, was not seen. The rate of SGA, defined as below the 10^th percentile, was slightly higher in the treatment group (11.2% vs. 10.4%), but the difference did not approach significance (P = 0.76).

By answering this long-pending question, the CHAP data are “practice changing,” declared an ACC-invited commentator, Athena Poppas, MD, chief of cardiology and director of the Lifespan Cardiovascular Institute, Providence, R.I. She agreed that the need for treatment of mild chronic hypertension has been a dilemma for clinicians that is now acceptably resolved.

In this trial, 2,408 pregnant women with chronic mild hypertension defined as a blood pressure of 160/90 mm Hg were randomized to treatment with a goal blood pressure of less than 140/90 mm Hg or no treatment unless the blood pressure rose to at least 160/105. All women had singleton pregnancies. Enrollment before 23 weeks of gestation was required. Severe hypertension (at least 160/105 mm Hg) was an exclusion criterion, as were several comorbidities, such as kidney disease.
 

Combination therapy accepted for <140/90 mm Hg goal

The beta-blocker labetalol or the calcium channel blocker nifedipine as single agents were the preferred antihypertensive medications in the protocol, but other medications were permitted. To reach the blood pressure goal, the single-agent therapy was titrated to the maximum dose before starting a second agent.

After randomization the systolic and diastolic blood pressures fell in both groups, but they fell more and remained consistently lower in the active treatment group, particularly during the first 20 weeks after randomization, according to graphs displayed by Dr. Tita. Over the course of the study, the mean diastolic blood pressures were 129.5 and 132.6 mm Hg in the active treatment and control groups, respectively, while the systolic pressures were 79.1 vs. 81.5 mm Hg.

When the components of the primary outcome were evaluated separately, the greatest advantage of treatment was the reduction in the rate of severe eclampsia (23.3% vs. 29.1%; HR, 0.80: 95% confidence interval, 0.70-0.92) and preterm birth (12.2% vs. 16.7%; HR, 0.73: 95% CI, 0.60-0.89).

Across a large array of subgroups, including those with or without diabetes and those treated before or after 14 weeks of gestation, there was a consistent advantage for treatment, even if not statistically different. It is notable that 48% of patients were Black and 35% had a body mass index of at least 40. The active treatment was favored across all groups stratified by these characteristics.

Although the incidences of placental abruption (1.7% on treatment vs. 1.9% without) and fetal or neonatal death (3.5% vs. 4.3%) were lower in the active treatment group, they were uncommon events in both arms of the study. The differences did not reach statistical significance.
 

Maternal morbidity rates lower on treatment

Severe SGA, which was defined as below the 5^th percentile, was also numerically but not significantly higher in the control arm than in the group receiving treatment (5.1% vs. 5.5%), but the incidence of composite adverse maternal events was numerically lower (2.1% vs. 2.8%). The incidences of all components of maternal morbidity, such as maternal death (0.1% vs. 0.2%) pulmonary edema (0.4% vs. 0.9%), heart failure (0.1% vs. 0.1%), and acute kidney injury (0.8% vs. 1.2%), were either lower or the same on active treatment versus no treatment.

According to Dr. Tita, who called CHAP one of the largest and most diverse studies to address the value of treating mild hypertension in pregnancy, the American College of Obstetricians and Gynecologists (ACOG) is evaluating these data for changing their current guidelines for managing hypertension during pregnancy.

“The rate of chronic hypertension during pregnancy has been rising in the United States due to the increase in the average age of pregnant women and the rising rates of obesity,” Dr. Tita commented.

“We definitely needed these data,” said Mary Norine Walsh, MD, medical director, Ascension Saint Vincent Cardiovascular Research Institute, Indianapolis. Not only has the value of treating mild hypertension been unresolved, but Dr. Walsh pointed out that the rates of maternal mortality in the United States are rising and now generally exceed those of many other developed countries.

There are several features in the design of this trial that make the results even more salient to clinical practice, according to Dr. Walsh. This includes the fact that about half of patients enrolled were on Medicaid. As a result, the study confirmed benefit in what Dr. Walsh characterized as a “vulnerable” population.

“We will be busy now to make sure that our [pregnant] patients are achieving these target blood pressures,” Dr. Walsh said. She indicated that CHAP validates the treatment target of 140/90 mm Hg as a standard of care.

The results were published in the New England Journal of Medicine simultaneously with its ACC presentation.

The trial was funded by the National Heart, Lung, and Blood Institute. Dr. Tita reports research grants from Pfizer. Dr. Walsh reports a financial relationship with EBR Systems. Dr. Poppas reports no potential conflicts of interest.

Pregnant women with even mild hypertension should receive blood pressure–lowering medications to reduce the likelihood of adverse outcomes for the mother and the child, according to a large, open-label, randomized trial.

“Treating to the blood pressure goal in this study reduced the risk of adverse events associated with pregnancy but did not impair fetal growth,” Alan T. Tita, MD, PhD, associate dean for Global and Women’s Health, University of Alabama, Birmingham, reported at the annual scientific sessions of the American College of Cardiology.

The question of whether to treat chronic hypertension during pregnancy has been “an international controversy for decades,” said Dr. Tita, who led the investigator-initiated Chronic Hypertension and Pregnancy (CHAP) trial.

For the composite primary outcome of severe preeclampsia, medically indicated preterm birth at less than 35 weeks of gestation, placental abruption, or fetal/neonatal death, the treatment of hypertension versus no treatment showed a relative risk reduction of 18% (30.2% vs. 37%, (hazard ratio, 0.82; P < .001).
 

Small for gestational age is primary safety endpoint

An increase in preeclampsia risk in women whose fetus was small for gestational age (SGA), a theoretical consequence of reductions in arterial pressure, was not seen. The rate of SGA, defined as below the 10^th percentile, was slightly higher in the treatment group (11.2% vs. 10.4%), but the difference did not approach significance (P = 0.76).

By answering this long-pending question, the CHAP data are “practice changing,” declared an ACC-invited commentator, Athena Poppas, MD, chief of cardiology and director of the Lifespan Cardiovascular Institute, Providence, R.I. She agreed that the need for treatment of mild chronic hypertension has been a dilemma for clinicians that is now acceptably resolved.

In this trial, 2,408 pregnant women with chronic mild hypertension defined as a blood pressure of 160/90 mm Hg were randomized to treatment with a goal blood pressure of less than 140/90 mm Hg or no treatment unless the blood pressure rose to at least 160/105. All women had singleton pregnancies. Enrollment before 23 weeks of gestation was required. Severe hypertension (at least 160/105 mm Hg) was an exclusion criterion, as were several comorbidities, such as kidney disease.
 

Combination therapy accepted for <140/90 mm Hg goal

The beta-blocker labetalol or the calcium channel blocker nifedipine as single agents were the preferred antihypertensive medications in the protocol, but other medications were permitted. To reach the blood pressure goal, the single-agent therapy was titrated to the maximum dose before starting a second agent.

After randomization the systolic and diastolic blood pressures fell in both groups, but they fell more and remained consistently lower in the active treatment group, particularly during the first 20 weeks after randomization, according to graphs displayed by Dr. Tita. Over the course of the study, the mean diastolic blood pressures were 129.5 and 132.6 mm Hg in the active treatment and control groups, respectively, while the systolic pressures were 79.1 vs. 81.5 mm Hg.

When the components of the primary outcome were evaluated separately, the greatest advantage of treatment was the reduction in the rate of severe eclampsia (23.3% vs. 29.1%; HR, 0.80: 95% confidence interval, 0.70-0.92) and preterm birth (12.2% vs. 16.7%; HR, 0.73: 95% CI, 0.60-0.89).

Across a large array of subgroups, including those with or without diabetes and those treated before or after 14 weeks of gestation, there was a consistent advantage for treatment, even if not statistically different. It is notable that 48% of patients were Black and 35% had a body mass index of at least 40. The active treatment was favored across all groups stratified by these characteristics.

Although the incidences of placental abruption (1.7% on treatment vs. 1.9% without) and fetal or neonatal death (3.5% vs. 4.3%) were lower in the active treatment group, they were uncommon events in both arms of the study. The differences did not reach statistical significance.
 

Maternal morbidity rates lower on treatment

Severe SGA, which was defined as below the 5^th percentile, was also numerically but not significantly higher in the control arm than in the group receiving treatment (5.1% vs. 5.5%), but the incidence of composite adverse maternal events was numerically lower (2.1% vs. 2.8%). The incidences of all components of maternal morbidity, such as maternal death (0.1% vs. 0.2%) pulmonary edema (0.4% vs. 0.9%), heart failure (0.1% vs. 0.1%), and acute kidney injury (0.8% vs. 1.2%), were either lower or the same on active treatment versus no treatment.

According to Dr. Tita, who called CHAP one of the largest and most diverse studies to address the value of treating mild hypertension in pregnancy, the American College of Obstetricians and Gynecologists (ACOG) is evaluating these data for changing their current guidelines for managing hypertension during pregnancy.

“The rate of chronic hypertension during pregnancy has been rising in the United States due to the increase in the average age of pregnant women and the rising rates of obesity,” Dr. Tita commented.

“We definitely needed these data,” said Mary Norine Walsh, MD, medical director, Ascension Saint Vincent Cardiovascular Research Institute, Indianapolis. Not only has the value of treating mild hypertension been unresolved, but Dr. Walsh pointed out that the rates of maternal mortality in the United States are rising and now generally exceed those of many other developed countries.

There are several features in the design of this trial that make the results even more salient to clinical practice, according to Dr. Walsh. This includes the fact that about half of patients enrolled were on Medicaid. As a result, the study confirmed benefit in what Dr. Walsh characterized as a “vulnerable” population.

“We will be busy now to make sure that our [pregnant] patients are achieving these target blood pressures,” Dr. Walsh said. She indicated that CHAP validates the treatment target of 140/90 mm Hg as a standard of care.

The results were published in the New England Journal of Medicine simultaneously with its ACC presentation.

The trial was funded by the National Heart, Lung, and Blood Institute. Dr. Tita reports research grants from Pfizer. Dr. Walsh reports a financial relationship with EBR Systems. Dr. Poppas reports no potential conflicts of interest.

A low-sodium diet was not associated with a reduction in future clinical events in a new study in ambulatory patients with heart failure. But there was a moderate benefit on quality of life and New York Heart Association (NYHA) functional class.

“The guidelines used to strongly recommend a reduction in sodium intake in heart failure patients, but this advice has backed off in recent years because of the lack of data. Most heart failure guidelines now do not make any recommendations on dietary sodium,” he said.

SODIUM-HF was a pragmatic, multinational, open-label, randomized trial conducted in six countries (Australia, Canada, Chile, Colombia, Mexico, and New Zealand), which included 809 patients (median age, 67 years) with chronic heart failure (NYHA functional class II–III) who were receiving optimally tolerated guideline-directed medical treatment. They were randomly assigned to usual care according to local guidelines or a low-sodium diet of less than 100 mmol (<1,500 mg/day). Patients with a baseline sodium intake of less than 1,500 mg/day were excluded.

In the intervention group, patients were asked to follow low-sodium menus developed by dietitians localized to each region. They also received behavioral counseling by trained dietitians or physicians or nurses.

Dietary sodium intake was assessed by using a 3-day food record (including 1 weekend day) at baseline, 6 months, and 12 months in both groups and, for the intervention group, also at 3 and 9 months to monitor and support dietary adherence.

Dr. Ezekowitz explained that although the best method for measuring sodium levels would normally be a 24-hour urine sodium, this would be impractical in a large clinical trial. In addition, he pointed out that urinary sodium is not an accurate measure of actual sodium levels in patients taking diuretics, so it is not a good measure to use in a heart failure population.

“The food record method of assessing sodium levels has been well validated; I think we measured it as accurately as we could have done,” he added.

Results showed that between baseline and 12 months, the median sodium intake decreased from 2,286 mg/day to 1,658 mg/day in the low-sodium group and from 2,119 mg/day to 2,073 mg/day in the usual care group. The median difference between groups was 415 mg/day at 12 months.

By 12 months, events comprising the primary outcome (hospitalization or emergency department visits due to cardiovascular causes or all-cause death) had occurred in 15% of patients in the low-sodium diet group and 17% of those in the usual care group (hazard ratio [HR], 0.89 [95% CI, 0.63 - 1.26]; P = .53).

All-cause death occurred in 6% of patients in the low-sodium diet group and 4% of those in the usual care group (HR, 1.38; P = .32). Cardiovascular-related hospitalization occurred in 10% of the low-sodium group and 12% of the usual care group (HR, 0.82; P = .36), and cardiovascular-related emergency department visits occurred in 4% of both groups (HR, 1.21; P = .60).

The absence of treatment effect for the primary outcome was consistent across most prespecified subgroups, including those with higher vs lower baseline sodium intake. But there was a suggestion of a greater reduction in the primary outcome in individuals younger than age 65 years than in those age 65 years and older.

Quality-of-life measures on the Kansas City Cardiomyopathy Questionnaire (KCCQ) suggested a benefit in the low-sodium group, with mean between-group differences in the change from baseline to 12 months of 3.38 points in the overall summary score, 3.29 points in the clinical summary score, and 3.77 points in the physical limitation score (all differences were statistically significant).

There was no significant difference in 6-minute-walk distance at 12 months between the low-sodium diet group and the usual care group.

NYHA functional class at 12 months differed significantly between groups; the low-sodium diet group had a greater likelihood of improving by one NYHA class than the usual care group (odds ratio, 0.59; P = .0061).

No safety events related to the study treatment were reported in either group.

Dr. Ezekowitz said that to investigate whether longer follow-up may show a difference in events, further analyses are planned at 2 years and 5 years.

Questions on food recall and blinding

Commenting on the findings at the late-breaking clinical trials session at the ACC meeting, Biykem Bozkurt, MD, professor of medicine at Baylor College of Medicine, Houston, congratulated Dr. Ezekowitz on conducting this trial.

“We have been chasing the holy grail of sodium reduction in heart failure for a very long time, so I have to commend you and your team for taking on this challenge, especially during the pandemic,” she said.

But Dr. Bozkurt questioned whether the intervention group actually had a meaningful sodium reduction given that this was measured by food recall and this may have been accounted for by under-reporting of certain food intakes.

Dr. Ezekowitz responded that patients acted as their own controls in that calorie intake, fluid intake, and weight were also assessed and did not change. “So I think we did have a meaningful reduction in sodium,” he said.

Dr. Bozkurt also queried whether the improvements in quality of life and functional status were reliable given that this was an unblinded study.

To this point, Dr. Ezekowitz pointed out that the KCCQ quality-of-life measure was a highly validated instrument and that improvements were seen in these measures at 3, 6, and 12 months. “It is not like these were spurious findings, so I think we have to look at this as a real result,” he argued.

Commenting on the study at an ACC press conference, Mary Norine Walsh, MD, director of the heart failure and cardiac transplantation programs at St. Vincent Heart Center in Indianapolis, said the trial had answered two important questions: that sodium reduction in heart failure may not reduce heart failure hospitalization/death but that patients feel better.

“I think we can safely tell patients that if they slip up a bit they may not end up in hospital,” she added.

This study was funded by the Canadian Institutes of Health Research and the University Hospital Foundation (Edmonton, Alberta, Canada) and the Health Research Council of New Zealand. Dr. Ezekowitz reports research grants from American Regent, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, eko.ai, US2.ai, Merck, Novartis, Otsuka, Sanofi, and Servier and consulting fees from American Regent, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, Merck, Novartis, Otsuka, Sanofi, and Servier.

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

A low-sodium diet was not associated with a reduction in future clinical events in a new study in ambulatory patients with heart failure. But there was a moderate benefit on quality of life and New York Heart Association (NYHA) functional class.

“The guidelines used to strongly recommend a reduction in sodium intake in heart failure patients, but this advice has backed off in recent years because of the lack of data. Most heart failure guidelines now do not make any recommendations on dietary sodium,” he said.

SODIUM-HF was a pragmatic, multinational, open-label, randomized trial conducted in six countries (Australia, Canada, Chile, Colombia, Mexico, and New Zealand), which included 809 patients (median age, 67 years) with chronic heart failure (NYHA functional class II–III) who were receiving optimally tolerated guideline-directed medical treatment. They were randomly assigned to usual care according to local guidelines or a low-sodium diet of less than 100 mmol (<1,500 mg/day). Patients with a baseline sodium intake of less than 1,500 mg/day were excluded.

In the intervention group, patients were asked to follow low-sodium menus developed by dietitians localized to each region. They also received behavioral counseling by trained dietitians or physicians or nurses.

Dietary sodium intake was assessed by using a 3-day food record (including 1 weekend day) at baseline, 6 months, and 12 months in both groups and, for the intervention group, also at 3 and 9 months to monitor and support dietary adherence.

Dr. Ezekowitz explained that although the best method for measuring sodium levels would normally be a 24-hour urine sodium, this would be impractical in a large clinical trial. In addition, he pointed out that urinary sodium is not an accurate measure of actual sodium levels in patients taking diuretics, so it is not a good measure to use in a heart failure population.

“The food record method of assessing sodium levels has been well validated; I think we measured it as accurately as we could have done,” he added.

Results showed that between baseline and 12 months, the median sodium intake decreased from 2,286 mg/day to 1,658 mg/day in the low-sodium group and from 2,119 mg/day to 2,073 mg/day in the usual care group. The median difference between groups was 415 mg/day at 12 months.

By 12 months, events comprising the primary outcome (hospitalization or emergency department visits due to cardiovascular causes or all-cause death) had occurred in 15% of patients in the low-sodium diet group and 17% of those in the usual care group (hazard ratio [HR], 0.89 [95% CI, 0.63 - 1.26]; P = .53).

All-cause death occurred in 6% of patients in the low-sodium diet group and 4% of those in the usual care group (HR, 1.38; P = .32). Cardiovascular-related hospitalization occurred in 10% of the low-sodium group and 12% of the usual care group (HR, 0.82; P = .36), and cardiovascular-related emergency department visits occurred in 4% of both groups (HR, 1.21; P = .60).

The absence of treatment effect for the primary outcome was consistent across most prespecified subgroups, including those with higher vs lower baseline sodium intake. But there was a suggestion of a greater reduction in the primary outcome in individuals younger than age 65 years than in those age 65 years and older.

Quality-of-life measures on the Kansas City Cardiomyopathy Questionnaire (KCCQ) suggested a benefit in the low-sodium group, with mean between-group differences in the change from baseline to 12 months of 3.38 points in the overall summary score, 3.29 points in the clinical summary score, and 3.77 points in the physical limitation score (all differences were statistically significant).

There was no significant difference in 6-minute-walk distance at 12 months between the low-sodium diet group and the usual care group.

NYHA functional class at 12 months differed significantly between groups; the low-sodium diet group had a greater likelihood of improving by one NYHA class than the usual care group (odds ratio, 0.59; P = .0061).

No safety events related to the study treatment were reported in either group.

Dr. Ezekowitz said that to investigate whether longer follow-up may show a difference in events, further analyses are planned at 2 years and 5 years.

Questions on food recall and blinding

Commenting on the findings at the late-breaking clinical trials session at the ACC meeting, Biykem Bozkurt, MD, professor of medicine at Baylor College of Medicine, Houston, congratulated Dr. Ezekowitz on conducting this trial.

“We have been chasing the holy grail of sodium reduction in heart failure for a very long time, so I have to commend you and your team for taking on this challenge, especially during the pandemic,” she said.

But Dr. Bozkurt questioned whether the intervention group actually had a meaningful sodium reduction given that this was measured by food recall and this may have been accounted for by under-reporting of certain food intakes.

Dr. Ezekowitz responded that patients acted as their own controls in that calorie intake, fluid intake, and weight were also assessed and did not change. “So I think we did have a meaningful reduction in sodium,” he said.

Dr. Bozkurt also queried whether the improvements in quality of life and functional status were reliable given that this was an unblinded study.

To this point, Dr. Ezekowitz pointed out that the KCCQ quality-of-life measure was a highly validated instrument and that improvements were seen in these measures at 3, 6, and 12 months. “It is not like these were spurious findings, so I think we have to look at this as a real result,” he argued.

Commenting on the study at an ACC press conference, Mary Norine Walsh, MD, director of the heart failure and cardiac transplantation programs at St. Vincent Heart Center in Indianapolis, said the trial had answered two important questions: that sodium reduction in heart failure may not reduce heart failure hospitalization/death but that patients feel better.

“I think we can safely tell patients that if they slip up a bit they may not end up in hospital,” she added.

This study was funded by the Canadian Institutes of Health Research and the University Hospital Foundation (Edmonton, Alberta, Canada) and the Health Research Council of New Zealand. Dr. Ezekowitz reports research grants from American Regent, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, eko.ai, US2.ai, Merck, Novartis, Otsuka, Sanofi, and Servier and consulting fees from American Regent, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, Merck, Novartis, Otsuka, Sanofi, and Servier.

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

A low-sodium diet was not associated with a reduction in future clinical events in a new study in ambulatory patients with heart failure. But there was a moderate benefit on quality of life and New York Heart Association (NYHA) functional class.

“The guidelines used to strongly recommend a reduction in sodium intake in heart failure patients, but this advice has backed off in recent years because of the lack of data. Most heart failure guidelines now do not make any recommendations on dietary sodium,” he said.

SODIUM-HF was a pragmatic, multinational, open-label, randomized trial conducted in six countries (Australia, Canada, Chile, Colombia, Mexico, and New Zealand), which included 809 patients (median age, 67 years) with chronic heart failure (NYHA functional class II–III) who were receiving optimally tolerated guideline-directed medical treatment. They were randomly assigned to usual care according to local guidelines or a low-sodium diet of less than 100 mmol (<1,500 mg/day). Patients with a baseline sodium intake of less than 1,500 mg/day were excluded.

In the intervention group, patients were asked to follow low-sodium menus developed by dietitians localized to each region. They also received behavioral counseling by trained dietitians or physicians or nurses.

Dietary sodium intake was assessed by using a 3-day food record (including 1 weekend day) at baseline, 6 months, and 12 months in both groups and, for the intervention group, also at 3 and 9 months to monitor and support dietary adherence.

Dr. Ezekowitz explained that although the best method for measuring sodium levels would normally be a 24-hour urine sodium, this would be impractical in a large clinical trial. In addition, he pointed out that urinary sodium is not an accurate measure of actual sodium levels in patients taking diuretics, so it is not a good measure to use in a heart failure population.

“The food record method of assessing sodium levels has been well validated; I think we measured it as accurately as we could have done,” he added.

Results showed that between baseline and 12 months, the median sodium intake decreased from 2,286 mg/day to 1,658 mg/day in the low-sodium group and from 2,119 mg/day to 2,073 mg/day in the usual care group. The median difference between groups was 415 mg/day at 12 months.

By 12 months, events comprising the primary outcome (hospitalization or emergency department visits due to cardiovascular causes or all-cause death) had occurred in 15% of patients in the low-sodium diet group and 17% of those in the usual care group (hazard ratio [HR], 0.89 [95% CI, 0.63 - 1.26]; P = .53).

All-cause death occurred in 6% of patients in the low-sodium diet group and 4% of those in the usual care group (HR, 1.38; P = .32). Cardiovascular-related hospitalization occurred in 10% of the low-sodium group and 12% of the usual care group (HR, 0.82; P = .36), and cardiovascular-related emergency department visits occurred in 4% of both groups (HR, 1.21; P = .60).

The absence of treatment effect for the primary outcome was consistent across most prespecified subgroups, including those with higher vs lower baseline sodium intake. But there was a suggestion of a greater reduction in the primary outcome in individuals younger than age 65 years than in those age 65 years and older.

Quality-of-life measures on the Kansas City Cardiomyopathy Questionnaire (KCCQ) suggested a benefit in the low-sodium group, with mean between-group differences in the change from baseline to 12 months of 3.38 points in the overall summary score, 3.29 points in the clinical summary score, and 3.77 points in the physical limitation score (all differences were statistically significant).

There was no significant difference in 6-minute-walk distance at 12 months between the low-sodium diet group and the usual care group.

NYHA functional class at 12 months differed significantly between groups; the low-sodium diet group had a greater likelihood of improving by one NYHA class than the usual care group (odds ratio, 0.59; P = .0061).

No safety events related to the study treatment were reported in either group.

Dr. Ezekowitz said that to investigate whether longer follow-up may show a difference in events, further analyses are planned at 2 years and 5 years.

Questions on food recall and blinding

Commenting on the findings at the late-breaking clinical trials session at the ACC meeting, Biykem Bozkurt, MD, professor of medicine at Baylor College of Medicine, Houston, congratulated Dr. Ezekowitz on conducting this trial.

“We have been chasing the holy grail of sodium reduction in heart failure for a very long time, so I have to commend you and your team for taking on this challenge, especially during the pandemic,” she said.

But Dr. Bozkurt questioned whether the intervention group actually had a meaningful sodium reduction given that this was measured by food recall and this may have been accounted for by under-reporting of certain food intakes.

Dr. Ezekowitz responded that patients acted as their own controls in that calorie intake, fluid intake, and weight were also assessed and did not change. “So I think we did have a meaningful reduction in sodium,” he said.

Dr. Bozkurt also queried whether the improvements in quality of life and functional status were reliable given that this was an unblinded study.

To this point, Dr. Ezekowitz pointed out that the KCCQ quality-of-life measure was a highly validated instrument and that improvements were seen in these measures at 3, 6, and 12 months. “It is not like these were spurious findings, so I think we have to look at this as a real result,” he argued.

Commenting on the study at an ACC press conference, Mary Norine Walsh, MD, director of the heart failure and cardiac transplantation programs at St. Vincent Heart Center in Indianapolis, said the trial had answered two important questions: that sodium reduction in heart failure may not reduce heart failure hospitalization/death but that patients feel better.

“I think we can safely tell patients that if they slip up a bit they may not end up in hospital,” she added.

This study was funded by the Canadian Institutes of Health Research and the University Hospital Foundation (Edmonton, Alberta, Canada) and the Health Research Council of New Zealand. Dr. Ezekowitz reports research grants from American Regent, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, eko.ai, US2.ai, Merck, Novartis, Otsuka, Sanofi, and Servier and consulting fees from American Regent, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, Merck, Novartis, Otsuka, Sanofi, and Servier.

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

The risk for sudden cardiac death (SCD) climbs steadily in tandem with coronary artery calcium (CAC) burden, independent of more conventional risk factors, in primary-prevention patients considered low- to intermediate-risk, researchers say.

The findings, based on a large cohort study, strengthen the case for initial CAC imaging as a gatekeeper to further testing in such patients who have mostly subclinical atherosclerotic cardiovascular disease (ASCVD), they conclude.

The CAC scan is “evolving into a primary-prevention screening test, not only for initiating statin therapy, but now as a screening modality for risk stratifying someone for sudden cardiac arrest,” Alexander C. Razavi, MD, MPH, PhD, Johns Hopkins University School of Medicine, Baltimore, told this news organization.

“Our data reinforce this and give some quantitative measures of when we should start to consider that.”

A CAC score of 100 to 399 in this “primarily asymptomatic,” predominantly White and male cohort elevated the risk for SCD over an average of 10.6 years by a factor of 2.8, compared with a score of 0. The risk went up four times with CAC scores of 400-999, and almost five times with scores above 1,000.

The risk association was independent of age and sex but also diabetes, smoking, hypertension, dyslipidemia, and family history of heart disease.

That and other findings, Dr. Razavi said, suggest CAC scores in low- to intermediate-risk patients like those studied may sharpen SCD risk-stratification beyond what is possible using traditional risk factors.

Dr. Razavi is lead author on the study’s March 21 publication in JACC Cardiovascular Imaging, and is slated to present the results April 2 during the American College of Cardiology (ACC) 2022 Scientific Session, to be held virtually and in-person in Washington, D.C.

The study’s 66,636 primary-prevention patients, part of the Coronary Artery Calcium Consortium observational cohort, were without known coronary disease at enrollment, from 1991-2010, at four major American centers. They had been referred to CAC imaging because of the presence of at least one ASCVD risk factor, such as dyslipidemia, family history of premature heart disease, hypertension, or diabetes, the researchers note.

They observed 211 SCD events, for a rate of about 0.3%, over a median of 10.6 years. The adjusted stepwise higher risk (SHR) for an SCD event went up continuously with CAC scores (P for trend < .001). The SHR values, compared with a CAC score of 0, were:

• 1.3 (95% CI, 0.7-2.4) for a CAC score score of 1 to 99
• 2.8 (95% CI, 1.6-5.0) for a CAC score of 100 to 399
• 4.0 (95% CI, 2.2-7.3) for a CAC score of 400 to 999
• 4.9 (95% CI, 2.6-9.9) for a CAC score above 1,000

The magnitude of the CAC score’s association with SCD risk in the study was “surprising,” Dr. Razavi said. The CAC score, starting at about 100, seems “more strongly associated with a sudden cardiac arrest” than more familiar SCD risk predictors, such as prolonged heart-rate-corrected QT interval or QRS duration.

Dr. Razavi reported no conflicts. Disclosures for the other authors are in the report.

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

The risk for sudden cardiac death (SCD) climbs steadily in tandem with coronary artery calcium (CAC) burden, independent of more conventional risk factors, in primary-prevention patients considered low- to intermediate-risk, researchers say.

The findings, based on a large cohort study, strengthen the case for initial CAC imaging as a gatekeeper to further testing in such patients who have mostly subclinical atherosclerotic cardiovascular disease (ASCVD), they conclude.

The CAC scan is “evolving into a primary-prevention screening test, not only for initiating statin therapy, but now as a screening modality for risk stratifying someone for sudden cardiac arrest,” Alexander C. Razavi, MD, MPH, PhD, Johns Hopkins University School of Medicine, Baltimore, told this news organization.

“Our data reinforce this and give some quantitative measures of when we should start to consider that.”

A CAC score of 100 to 399 in this “primarily asymptomatic,” predominantly White and male cohort elevated the risk for SCD over an average of 10.6 years by a factor of 2.8, compared with a score of 0. The risk went up four times with CAC scores of 400-999, and almost five times with scores above 1,000.

The risk association was independent of age and sex but also diabetes, smoking, hypertension, dyslipidemia, and family history of heart disease.

That and other findings, Dr. Razavi said, suggest CAC scores in low- to intermediate-risk patients like those studied may sharpen SCD risk-stratification beyond what is possible using traditional risk factors.

Dr. Razavi is lead author on the study’s March 21 publication in JACC Cardiovascular Imaging, and is slated to present the results April 2 during the American College of Cardiology (ACC) 2022 Scientific Session, to be held virtually and in-person in Washington, D.C.

The study’s 66,636 primary-prevention patients, part of the Coronary Artery Calcium Consortium observational cohort, were without known coronary disease at enrollment, from 1991-2010, at four major American centers. They had been referred to CAC imaging because of the presence of at least one ASCVD risk factor, such as dyslipidemia, family history of premature heart disease, hypertension, or diabetes, the researchers note.

They observed 211 SCD events, for a rate of about 0.3%, over a median of 10.6 years. The adjusted stepwise higher risk (SHR) for an SCD event went up continuously with CAC scores (P for trend < .001). The SHR values, compared with a CAC score of 0, were:

• 1.3 (95% CI, 0.7-2.4) for a CAC score score of 1 to 99
• 2.8 (95% CI, 1.6-5.0) for a CAC score of 100 to 399
• 4.0 (95% CI, 2.2-7.3) for a CAC score of 400 to 999
• 4.9 (95% CI, 2.6-9.9) for a CAC score above 1,000

The magnitude of the CAC score’s association with SCD risk in the study was “surprising,” Dr. Razavi said. The CAC score, starting at about 100, seems “more strongly associated with a sudden cardiac arrest” than more familiar SCD risk predictors, such as prolonged heart-rate-corrected QT interval or QRS duration.

Dr. Razavi reported no conflicts. Disclosures for the other authors are in the report.

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

The risk for sudden cardiac death (SCD) climbs steadily in tandem with coronary artery calcium (CAC) burden, independent of more conventional risk factors, in primary-prevention patients considered low- to intermediate-risk, researchers say.

The findings, based on a large cohort study, strengthen the case for initial CAC imaging as a gatekeeper to further testing in such patients who have mostly subclinical atherosclerotic cardiovascular disease (ASCVD), they conclude.

The CAC scan is “evolving into a primary-prevention screening test, not only for initiating statin therapy, but now as a screening modality for risk stratifying someone for sudden cardiac arrest,” Alexander C. Razavi, MD, MPH, PhD, Johns Hopkins University School of Medicine, Baltimore, told this news organization.

“Our data reinforce this and give some quantitative measures of when we should start to consider that.”

A CAC score of 100 to 399 in this “primarily asymptomatic,” predominantly White and male cohort elevated the risk for SCD over an average of 10.6 years by a factor of 2.8, compared with a score of 0. The risk went up four times with CAC scores of 400-999, and almost five times with scores above 1,000.

The risk association was independent of age and sex but also diabetes, smoking, hypertension, dyslipidemia, and family history of heart disease.

That and other findings, Dr. Razavi said, suggest CAC scores in low- to intermediate-risk patients like those studied may sharpen SCD risk-stratification beyond what is possible using traditional risk factors.

Dr. Razavi is lead author on the study’s March 21 publication in JACC Cardiovascular Imaging, and is slated to present the results April 2 during the American College of Cardiology (ACC) 2022 Scientific Session, to be held virtually and in-person in Washington, D.C.

The study’s 66,636 primary-prevention patients, part of the Coronary Artery Calcium Consortium observational cohort, were without known coronary disease at enrollment, from 1991-2010, at four major American centers. They had been referred to CAC imaging because of the presence of at least one ASCVD risk factor, such as dyslipidemia, family history of premature heart disease, hypertension, or diabetes, the researchers note.

They observed 211 SCD events, for a rate of about 0.3%, over a median of 10.6 years. The adjusted stepwise higher risk (SHR) for an SCD event went up continuously with CAC scores (P for trend < .001). The SHR values, compared with a CAC score of 0, were:

• 1.3 (95% CI, 0.7-2.4) for a CAC score score of 1 to 99
• 2.8 (95% CI, 1.6-5.0) for a CAC score of 100 to 399
• 4.0 (95% CI, 2.2-7.3) for a CAC score of 400 to 999
• 4.9 (95% CI, 2.6-9.9) for a CAC score above 1,000

The magnitude of the CAC score’s association with SCD risk in the study was “surprising,” Dr. Razavi said. The CAC score, starting at about 100, seems “more strongly associated with a sudden cardiac arrest” than more familiar SCD risk predictors, such as prolonged heart-rate-corrected QT interval or QRS duration.

Dr. Razavi reported no conflicts. Disclosures for the other authors are in the report.

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