Cardiology

Catheter ablation has been around a lot longer for ventricular arrhythmia than for atrial fibrillation, but far less is settled about what antithrombotic therapy should follow ventricular ablations, as there have been no big, randomized trials for guidance.

But the evidence base grew stronger this week, and it favors postprocedure treatment with a direct oral anticoagulant (DOAC) over antiplatelet therapy with aspirin for patients undergoing radiofrequency (RF) ablation to treat left ventricular (LV) arrhythmias.

The 30-day risk for ischemic stroke or transient ischemia attack (TIA) was sharply higher for patients who took daily aspirin after RF ablation for ventricular tachycardia (VT) or premature ventricular contractions (PVC) in a multicenter randomized trial.

Those of its 246 patients who received aspirin were also far more likely to show asymptomatic lesions on cerebral MRI scans performed both 24 hours and 30 days after the procedure.

The findings show the importance of DOAC therapy after ventricular ablation procedures, a setting for which there are no evidence-based guidelines, “to mitigate the risk of systemic thromboembolic events,” said Dhanunjaya Lakkireddy, MD, Kansas City Heart Rhythm Institute, Overland Park. He spoke at a media presentation on the trial, called STROKE-VT, during the Heart Rhythm Society 2021 Scientific Sessions, held virtually and on-site in Boston.

The risk for stroke and TIA went up in association with several procedural issues, including some that operators might be able to change in order to reach for better outcomes, Dr. Lakkireddy observed.

“Prolonged radiofrequency ablation times, especially in those with low left ventricle ejection fractions, are definitely higher risk,” as are procedures that involved the retrograde transaortic approach for advancing the ablation catheter, rather than a trans-septal approach.

The retrograde transaortic approach should be avoided in such procedures, “whenever it can be avoided,” said Dr. Lakkireddy, who formally presented STROKE-VT at the HRS sessions and is lead author on its report published about the same time in JACC: Clinical Electrophysiology.

The trial has limitations, but “it’s a very important study, and I think that this could become our standard of care for managing anticoagulation after VT and PVC left-sided ablations,” Mina K. Chung, MD, Cleveland Clinic, said as an invited discussant after Dr. Lakkireddy’s presentation.

How patients are treated with antithrombotics after ventricular ablations can vary widely, sometimes based on the operator’s “subjective feeling of how extensive the ablation is,” Christine M. Albert, MD, MPH, Cedars-Sinai Medical Center, Los Angeles, not involved in the study, said during the STROKE-VT media briefing.

That’s consistent with the guidelines, which propose oral anticoagulation therapy after more extensive ventricular ablations and antiplatelets when the ablation is more limited – based more on consensus than firm evidence – as described by Jeffrey R. Winterfield, MD, Medical University of South Carolina, Charleston, and Usha Tedrow, MD, MSc, Brigham and Women’s Hospital, Boston, in an accompanying editorial.

“This is really the first randomized trial data, that I know of, that we have on this. So I do think it will be guideline-influencing,” Dr. Albert said.

“This should change practice,” agreed Jonathan P. Piccini, MD, MHS, Duke University, Durham, N.C., also not part of STROKE-VT. “A lot of evidence in the trial is consistent and provides a compelling story, not to mention that, in my opinion, the study probably underestimates the value of DOACs,” he told this news organization.

That’s because patients assigned to DOACs had far longer ablation times, “so their risk was even greater than in the aspirin arm,” Dr. Piccini said. Ablation times averaged 2,095 seconds in the DOAC group, compared with only 1,708 seconds in the aspirin group, probably because the preponderance of VT over PVC ablations for those getting a DOAC was even greater in the aspirin group.

Of the 246 patients assigned to either aspirin or a DOAC, usually a factor Xa inhibitor, 75% had undergone VT ablation and the remainder ablation for PVCs. Their mean age was 60 years and only 18% were women. None had experienced a cerebrovascular event in the previous 3 months.

The 30-day odds ratio for TIA or ischemic stroke in patients who received aspirin, compared with a DOAC, was 12.6 (95% confidence interval, 4.10-39.11; P < .001).

The corresponding OR for asymptomatic cerebral lesions by MRI at 24 hours was 2.15 (95% CI, 1.02-4.54; P = .04) and at 30 days was 3.48 (95% CI, 1.38-8.80; P = .008).

The rate of stroke or TIA was similar in patients who underwent ablation for VT and for PVCs (14% vs. 16%, respectively; P = .70). There were fewer asymptomatic cerebrovascular events by MRI at 24 hours for those undergoing VT ablations (14.7% and 25.8%, respectively; P = .046); but difference between rates attenuated by 30 days (11.4% and 14.5%, respectively; P = .52).

The OR for TIA or stroke associated with the retrograde transaortic approach, performed in about 40% of the patients, compared with the trans-septal approach in the remainder was 2.60 (95% CI, 1.06-6.37; P = .04).

“The study tells us it’s safe and indeed preferable to anticoagulate after an ablation procedure. But the more important finding, perhaps, wasn’t the one related to the core hypothesis. And that was the effect of retrograde access,” Paul A. Friedman, MD, Mayo Clinic, Rochester, Minn., said as an invited discussant after Dr. Lakkireddy’s formal presentation of the trial.

Whether a ventricular ablation is performed using the retrograde transaortic or trans-septal approach often depends on the location of the ablation targets in the left ventricle. But in some cases it’s a matter of operator preference, Dr. Piccini observed.

“There are some situations where, really, it is better to do retrograde aortic, and there are some cases that are better to do trans-septal. But now there’s going to be a higher burden of proof,” he said. Given the findings of STROKE-VT, operators may need to consider that a ventricular ablation procedure that can be done by the trans-septal route perhaps ought to be consistently done that way.

Dr. Lakkireddy discloses financial relationships with Boston Scientific, Biosense Webster, Janssen Pharmaceuticals, and more. Dr. Chung had “nothing relevant to disclose.” Dr. Piccini discloses receiving honoraria or speaking or consulting fees from Sanofi, Abbott, ARCA Biopharma, Medtronic, Philips, Biotronik, Allergan, LivaNova, and Myokardia; and research in conjunction with Bayer Healthcare, Abbott, Boston Scientific, and Philips. Dr. Friedman discloses conducting research in conjunction with Medtronic and Abbott; holding intellectual property rights with AliveCor, Inference, Medicool, Eko, and Anumana; and receiving honoraria or speaking or consulting fees from Boston Scientific. Dr. Winterfield and Dr. Tedrow had no disclosures.

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

Catheter ablation has been around a lot longer for ventricular arrhythmia than for atrial fibrillation, but far less is settled about what antithrombotic therapy should follow ventricular ablations, as there have been no big, randomized trials for guidance.

But the evidence base grew stronger this week, and it favors postprocedure treatment with a direct oral anticoagulant (DOAC) over antiplatelet therapy with aspirin for patients undergoing radiofrequency (RF) ablation to treat left ventricular (LV) arrhythmias.

The 30-day risk for ischemic stroke or transient ischemia attack (TIA) was sharply higher for patients who took daily aspirin after RF ablation for ventricular tachycardia (VT) or premature ventricular contractions (PVC) in a multicenter randomized trial.

Those of its 246 patients who received aspirin were also far more likely to show asymptomatic lesions on cerebral MRI scans performed both 24 hours and 30 days after the procedure.

The findings show the importance of DOAC therapy after ventricular ablation procedures, a setting for which there are no evidence-based guidelines, “to mitigate the risk of systemic thromboembolic events,” said Dhanunjaya Lakkireddy, MD, Kansas City Heart Rhythm Institute, Overland Park. He spoke at a media presentation on the trial, called STROKE-VT, during the Heart Rhythm Society 2021 Scientific Sessions, held virtually and on-site in Boston.

The risk for stroke and TIA went up in association with several procedural issues, including some that operators might be able to change in order to reach for better outcomes, Dr. Lakkireddy observed.

“Prolonged radiofrequency ablation times, especially in those with low left ventricle ejection fractions, are definitely higher risk,” as are procedures that involved the retrograde transaortic approach for advancing the ablation catheter, rather than a trans-septal approach.

The retrograde transaortic approach should be avoided in such procedures, “whenever it can be avoided,” said Dr. Lakkireddy, who formally presented STROKE-VT at the HRS sessions and is lead author on its report published about the same time in JACC: Clinical Electrophysiology.

The trial has limitations, but “it’s a very important study, and I think that this could become our standard of care for managing anticoagulation after VT and PVC left-sided ablations,” Mina K. Chung, MD, Cleveland Clinic, said as an invited discussant after Dr. Lakkireddy’s presentation.

How patients are treated with antithrombotics after ventricular ablations can vary widely, sometimes based on the operator’s “subjective feeling of how extensive the ablation is,” Christine M. Albert, MD, MPH, Cedars-Sinai Medical Center, Los Angeles, not involved in the study, said during the STROKE-VT media briefing.

That’s consistent with the guidelines, which propose oral anticoagulation therapy after more extensive ventricular ablations and antiplatelets when the ablation is more limited – based more on consensus than firm evidence – as described by Jeffrey R. Winterfield, MD, Medical University of South Carolina, Charleston, and Usha Tedrow, MD, MSc, Brigham and Women’s Hospital, Boston, in an accompanying editorial.

“This is really the first randomized trial data, that I know of, that we have on this. So I do think it will be guideline-influencing,” Dr. Albert said.

“This should change practice,” agreed Jonathan P. Piccini, MD, MHS, Duke University, Durham, N.C., also not part of STROKE-VT. “A lot of evidence in the trial is consistent and provides a compelling story, not to mention that, in my opinion, the study probably underestimates the value of DOACs,” he told this news organization.

That’s because patients assigned to DOACs had far longer ablation times, “so their risk was even greater than in the aspirin arm,” Dr. Piccini said. Ablation times averaged 2,095 seconds in the DOAC group, compared with only 1,708 seconds in the aspirin group, probably because the preponderance of VT over PVC ablations for those getting a DOAC was even greater in the aspirin group.

Of the 246 patients assigned to either aspirin or a DOAC, usually a factor Xa inhibitor, 75% had undergone VT ablation and the remainder ablation for PVCs. Their mean age was 60 years and only 18% were women. None had experienced a cerebrovascular event in the previous 3 months.

The 30-day odds ratio for TIA or ischemic stroke in patients who received aspirin, compared with a DOAC, was 12.6 (95% confidence interval, 4.10-39.11; P < .001).

The corresponding OR for asymptomatic cerebral lesions by MRI at 24 hours was 2.15 (95% CI, 1.02-4.54; P = .04) and at 30 days was 3.48 (95% CI, 1.38-8.80; P = .008).

The rate of stroke or TIA was similar in patients who underwent ablation for VT and for PVCs (14% vs. 16%, respectively; P = .70). There were fewer asymptomatic cerebrovascular events by MRI at 24 hours for those undergoing VT ablations (14.7% and 25.8%, respectively; P = .046); but difference between rates attenuated by 30 days (11.4% and 14.5%, respectively; P = .52).

The OR for TIA or stroke associated with the retrograde transaortic approach, performed in about 40% of the patients, compared with the trans-septal approach in the remainder was 2.60 (95% CI, 1.06-6.37; P = .04).

“The study tells us it’s safe and indeed preferable to anticoagulate after an ablation procedure. But the more important finding, perhaps, wasn’t the one related to the core hypothesis. And that was the effect of retrograde access,” Paul A. Friedman, MD, Mayo Clinic, Rochester, Minn., said as an invited discussant after Dr. Lakkireddy’s formal presentation of the trial.

Whether a ventricular ablation is performed using the retrograde transaortic or trans-septal approach often depends on the location of the ablation targets in the left ventricle. But in some cases it’s a matter of operator preference, Dr. Piccini observed.

“There are some situations where, really, it is better to do retrograde aortic, and there are some cases that are better to do trans-septal. But now there’s going to be a higher burden of proof,” he said. Given the findings of STROKE-VT, operators may need to consider that a ventricular ablation procedure that can be done by the trans-septal route perhaps ought to be consistently done that way.

Dr. Lakkireddy discloses financial relationships with Boston Scientific, Biosense Webster, Janssen Pharmaceuticals, and more. Dr. Chung had “nothing relevant to disclose.” Dr. Piccini discloses receiving honoraria or speaking or consulting fees from Sanofi, Abbott, ARCA Biopharma, Medtronic, Philips, Biotronik, Allergan, LivaNova, and Myokardia; and research in conjunction with Bayer Healthcare, Abbott, Boston Scientific, and Philips. Dr. Friedman discloses conducting research in conjunction with Medtronic and Abbott; holding intellectual property rights with AliveCor, Inference, Medicool, Eko, and Anumana; and receiving honoraria or speaking or consulting fees from Boston Scientific. Dr. Winterfield and Dr. Tedrow had no disclosures.

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

Catheter ablation has been around a lot longer for ventricular arrhythmia than for atrial fibrillation, but far less is settled about what antithrombotic therapy should follow ventricular ablations, as there have been no big, randomized trials for guidance.

But the evidence base grew stronger this week, and it favors postprocedure treatment with a direct oral anticoagulant (DOAC) over antiplatelet therapy with aspirin for patients undergoing radiofrequency (RF) ablation to treat left ventricular (LV) arrhythmias.

The 30-day risk for ischemic stroke or transient ischemia attack (TIA) was sharply higher for patients who took daily aspirin after RF ablation for ventricular tachycardia (VT) or premature ventricular contractions (PVC) in a multicenter randomized trial.

Those of its 246 patients who received aspirin were also far more likely to show asymptomatic lesions on cerebral MRI scans performed both 24 hours and 30 days after the procedure.

The findings show the importance of DOAC therapy after ventricular ablation procedures, a setting for which there are no evidence-based guidelines, “to mitigate the risk of systemic thromboembolic events,” said Dhanunjaya Lakkireddy, MD, Kansas City Heart Rhythm Institute, Overland Park. He spoke at a media presentation on the trial, called STROKE-VT, during the Heart Rhythm Society 2021 Scientific Sessions, held virtually and on-site in Boston.

The risk for stroke and TIA went up in association with several procedural issues, including some that operators might be able to change in order to reach for better outcomes, Dr. Lakkireddy observed.

“Prolonged radiofrequency ablation times, especially in those with low left ventricle ejection fractions, are definitely higher risk,” as are procedures that involved the retrograde transaortic approach for advancing the ablation catheter, rather than a trans-septal approach.

The retrograde transaortic approach should be avoided in such procedures, “whenever it can be avoided,” said Dr. Lakkireddy, who formally presented STROKE-VT at the HRS sessions and is lead author on its report published about the same time in JACC: Clinical Electrophysiology.

The trial has limitations, but “it’s a very important study, and I think that this could become our standard of care for managing anticoagulation after VT and PVC left-sided ablations,” Mina K. Chung, MD, Cleveland Clinic, said as an invited discussant after Dr. Lakkireddy’s presentation.

How patients are treated with antithrombotics after ventricular ablations can vary widely, sometimes based on the operator’s “subjective feeling of how extensive the ablation is,” Christine M. Albert, MD, MPH, Cedars-Sinai Medical Center, Los Angeles, not involved in the study, said during the STROKE-VT media briefing.

That’s consistent with the guidelines, which propose oral anticoagulation therapy after more extensive ventricular ablations and antiplatelets when the ablation is more limited – based more on consensus than firm evidence – as described by Jeffrey R. Winterfield, MD, Medical University of South Carolina, Charleston, and Usha Tedrow, MD, MSc, Brigham and Women’s Hospital, Boston, in an accompanying editorial.

“This is really the first randomized trial data, that I know of, that we have on this. So I do think it will be guideline-influencing,” Dr. Albert said.

“This should change practice,” agreed Jonathan P. Piccini, MD, MHS, Duke University, Durham, N.C., also not part of STROKE-VT. “A lot of evidence in the trial is consistent and provides a compelling story, not to mention that, in my opinion, the study probably underestimates the value of DOACs,” he told this news organization.

That’s because patients assigned to DOACs had far longer ablation times, “so their risk was even greater than in the aspirin arm,” Dr. Piccini said. Ablation times averaged 2,095 seconds in the DOAC group, compared with only 1,708 seconds in the aspirin group, probably because the preponderance of VT over PVC ablations for those getting a DOAC was even greater in the aspirin group.

Of the 246 patients assigned to either aspirin or a DOAC, usually a factor Xa inhibitor, 75% had undergone VT ablation and the remainder ablation for PVCs. Their mean age was 60 years and only 18% were women. None had experienced a cerebrovascular event in the previous 3 months.

The 30-day odds ratio for TIA or ischemic stroke in patients who received aspirin, compared with a DOAC, was 12.6 (95% confidence interval, 4.10-39.11; P < .001).

The corresponding OR for asymptomatic cerebral lesions by MRI at 24 hours was 2.15 (95% CI, 1.02-4.54; P = .04) and at 30 days was 3.48 (95% CI, 1.38-8.80; P = .008).

The rate of stroke or TIA was similar in patients who underwent ablation for VT and for PVCs (14% vs. 16%, respectively; P = .70). There were fewer asymptomatic cerebrovascular events by MRI at 24 hours for those undergoing VT ablations (14.7% and 25.8%, respectively; P = .046); but difference between rates attenuated by 30 days (11.4% and 14.5%, respectively; P = .52).

The OR for TIA or stroke associated with the retrograde transaortic approach, performed in about 40% of the patients, compared with the trans-septal approach in the remainder was 2.60 (95% CI, 1.06-6.37; P = .04).

“The study tells us it’s safe and indeed preferable to anticoagulate after an ablation procedure. But the more important finding, perhaps, wasn’t the one related to the core hypothesis. And that was the effect of retrograde access,” Paul A. Friedman, MD, Mayo Clinic, Rochester, Minn., said as an invited discussant after Dr. Lakkireddy’s formal presentation of the trial.

Whether a ventricular ablation is performed using the retrograde transaortic or trans-septal approach often depends on the location of the ablation targets in the left ventricle. But in some cases it’s a matter of operator preference, Dr. Piccini observed.

“There are some situations where, really, it is better to do retrograde aortic, and there are some cases that are better to do trans-septal. But now there’s going to be a higher burden of proof,” he said. Given the findings of STROKE-VT, operators may need to consider that a ventricular ablation procedure that can be done by the trans-septal route perhaps ought to be consistently done that way.

Dr. Lakkireddy discloses financial relationships with Boston Scientific, Biosense Webster, Janssen Pharmaceuticals, and more. Dr. Chung had “nothing relevant to disclose.” Dr. Piccini discloses receiving honoraria or speaking or consulting fees from Sanofi, Abbott, ARCA Biopharma, Medtronic, Philips, Biotronik, Allergan, LivaNova, and Myokardia; and research in conjunction with Bayer Healthcare, Abbott, Boston Scientific, and Philips. Dr. Friedman discloses conducting research in conjunction with Medtronic and Abbott; holding intellectual property rights with AliveCor, Inference, Medicool, Eko, and Anumana; and receiving honoraria or speaking or consulting fees from Boston Scientific. Dr. Winterfield and Dr. Tedrow had no disclosures.

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

When it comes to dieting and heart health in patients who are also exercising, less is more, suggests a new study.

The authors of the paper, published in Circulation, found a link between greater vascular benefits and exercise with modest – rather than intense – calorie restriction (CR) in elderly individuals with obesity.

“The finding that higher-intensity calorie restriction may not be necessary or advised has important implications for weight loss recommendations,” noted Tina E. Brinkley, Ph.D., lead author of the study and associate professor of gerontology and geriatric medicine at the Sticht Center for Healthy Aging and Alzheimer’s Prevention at Wake Forest University in Winston-Salem, N.C.

It’s “not entirely clear” why greater calorie restriction did not translate to greater vascular benefit, but it “could be related in part to potentially adverse effects of severe CR on vascular function,” she noted. “These findings have important implications for reducing cardiovascular risk with nonpharmacological interventions in high-risk populations.”

Methods and findings

The study included 160 men and women aged 65-79 years, with a body mass index (BMI) of 30 to 45 kg/m². The subjects were randomized to one of three groups for 20 weeks of aerobic exercise only, aerobic exercise plus moderate CR, or aerobic exercise plus more intensive CR. Their exercise regimen involved 30 minutes of supervised treadmill walking for 4 days per week at 65%-70% of heart rate reserve.

Subjects in the moderate CR group decreased caloric intake by 250 kcals a day, while the intense calorie reduction group cut 600 kcals per day. Their meals contained less than 30% of calories from fat and at least 0.8 g of protein per kg of ideal body weight. They were also provided with supplemental calcium (1,200 mg/day) and vitamin D (800 IU/day).

Cardiovascular magnetic resonance imaging was used to assess various aspects of aortic structure and function, including aortic arch pulse wave velocity, aortic distensibility and dimensions, and periaortic fat.

Weight loss was greater among subjects with CR plus exercise, compared with that of patients in the exercise-only group. The degree of weight loss was not significantly different between those with moderate versus intense CR ( 8.02 kg vs. 8.98 kg).

Among the exercise-only group, researchers observed no changes in aortic stiffness. However, adding moderate CR significantly improved this measure, while intense CR did not.

Specifically, subjects in the moderate-CR group had a “robust” 21% increase in distensibility in the descending aorta (DA), and an 8% decrease in aortic arch pulse wave velocity, whereas there were no significant vascular changes in the intense-CR group.

Bests results seen in exercise plus modest CR group

“Collectively, these data suggest that combining exercise with modest CR (as opposed to more intensive CR or no CR) provides the greatest benefit for proximal aortic stiffness, while also optimizing weight loss and improvements in body composition and body fat distribution,” noted the authors in their paper.

“Our data support the growing number of studies indicating that intentional weight loss can be safe for older adults with obesity and extend our previous findings, suggesting that obesity may blunt the beneficial effects of exercise for not only cardiorespiratory fitness, but likely vascular health as well.”

William E. Kraus, MD, professor in the Department of Medicine, Division of Cardiology at Duke University Medical Center, in Durham, NC, described the study as important and interesting for several reasons.

“First, it demonstrates one can change aortic vascular function with a combined diet and exercise program, even in older, obese Americans. This implies it is never too late to make meaningful lifestyle changes that will benefit cardiovascular health,” he said. “Second, it is among an increasing number of studies demonstrating that more is not always better than less in exercise and diet lifestyle changes - and in fact the converse is true.” 

“This gives hope that more people can benefit from modest lifestyle changes - in this case following guidelines for physical activity and only a modest reduction of 250 kilocalories per day resulted in benefit,” Dr. Kraus added.

The authors of the paper and Dr. Kraus disclosed no conflicts of interest.

When it comes to dieting and heart health in patients who are also exercising, less is more, suggests a new study.

The authors of the paper, published in Circulation, found a link between greater vascular benefits and exercise with modest – rather than intense – calorie restriction (CR) in elderly individuals with obesity.

“The finding that higher-intensity calorie restriction may not be necessary or advised has important implications for weight loss recommendations,” noted Tina E. Brinkley, Ph.D., lead author of the study and associate professor of gerontology and geriatric medicine at the Sticht Center for Healthy Aging and Alzheimer’s Prevention at Wake Forest University in Winston-Salem, N.C.

It’s “not entirely clear” why greater calorie restriction did not translate to greater vascular benefit, but it “could be related in part to potentially adverse effects of severe CR on vascular function,” she noted. “These findings have important implications for reducing cardiovascular risk with nonpharmacological interventions in high-risk populations.”

Methods and findings

The study included 160 men and women aged 65-79 years, with a body mass index (BMI) of 30 to 45 kg/m². The subjects were randomized to one of three groups for 20 weeks of aerobic exercise only, aerobic exercise plus moderate CR, or aerobic exercise plus more intensive CR. Their exercise regimen involved 30 minutes of supervised treadmill walking for 4 days per week at 65%-70% of heart rate reserve.

Subjects in the moderate CR group decreased caloric intake by 250 kcals a day, while the intense calorie reduction group cut 600 kcals per day. Their meals contained less than 30% of calories from fat and at least 0.8 g of protein per kg of ideal body weight. They were also provided with supplemental calcium (1,200 mg/day) and vitamin D (800 IU/day).

Cardiovascular magnetic resonance imaging was used to assess various aspects of aortic structure and function, including aortic arch pulse wave velocity, aortic distensibility and dimensions, and periaortic fat.

Weight loss was greater among subjects with CR plus exercise, compared with that of patients in the exercise-only group. The degree of weight loss was not significantly different between those with moderate versus intense CR ( 8.02 kg vs. 8.98 kg).

Among the exercise-only group, researchers observed no changes in aortic stiffness. However, adding moderate CR significantly improved this measure, while intense CR did not.

Specifically, subjects in the moderate-CR group had a “robust” 21% increase in distensibility in the descending aorta (DA), and an 8% decrease in aortic arch pulse wave velocity, whereas there were no significant vascular changes in the intense-CR group.

Bests results seen in exercise plus modest CR group

“Collectively, these data suggest that combining exercise with modest CR (as opposed to more intensive CR or no CR) provides the greatest benefit for proximal aortic stiffness, while also optimizing weight loss and improvements in body composition and body fat distribution,” noted the authors in their paper.

“Our data support the growing number of studies indicating that intentional weight loss can be safe for older adults with obesity and extend our previous findings, suggesting that obesity may blunt the beneficial effects of exercise for not only cardiorespiratory fitness, but likely vascular health as well.”

William E. Kraus, MD, professor in the Department of Medicine, Division of Cardiology at Duke University Medical Center, in Durham, NC, described the study as important and interesting for several reasons.

“First, it demonstrates one can change aortic vascular function with a combined diet and exercise program, even in older, obese Americans. This implies it is never too late to make meaningful lifestyle changes that will benefit cardiovascular health,” he said. “Second, it is among an increasing number of studies demonstrating that more is not always better than less in exercise and diet lifestyle changes - and in fact the converse is true.” 

“This gives hope that more people can benefit from modest lifestyle changes - in this case following guidelines for physical activity and only a modest reduction of 250 kilocalories per day resulted in benefit,” Dr. Kraus added.

The authors of the paper and Dr. Kraus disclosed no conflicts of interest.

When it comes to dieting and heart health in patients who are also exercising, less is more, suggests a new study.

The authors of the paper, published in Circulation, found a link between greater vascular benefits and exercise with modest – rather than intense – calorie restriction (CR) in elderly individuals with obesity.

“The finding that higher-intensity calorie restriction may not be necessary or advised has important implications for weight loss recommendations,” noted Tina E. Brinkley, Ph.D., lead author of the study and associate professor of gerontology and geriatric medicine at the Sticht Center for Healthy Aging and Alzheimer’s Prevention at Wake Forest University in Winston-Salem, N.C.

It’s “not entirely clear” why greater calorie restriction did not translate to greater vascular benefit, but it “could be related in part to potentially adverse effects of severe CR on vascular function,” she noted. “These findings have important implications for reducing cardiovascular risk with nonpharmacological interventions in high-risk populations.”

Methods and findings

The study included 160 men and women aged 65-79 years, with a body mass index (BMI) of 30 to 45 kg/m². The subjects were randomized to one of three groups for 20 weeks of aerobic exercise only, aerobic exercise plus moderate CR, or aerobic exercise plus more intensive CR. Their exercise regimen involved 30 minutes of supervised treadmill walking for 4 days per week at 65%-70% of heart rate reserve.

Subjects in the moderate CR group decreased caloric intake by 250 kcals a day, while the intense calorie reduction group cut 600 kcals per day. Their meals contained less than 30% of calories from fat and at least 0.8 g of protein per kg of ideal body weight. They were also provided with supplemental calcium (1,200 mg/day) and vitamin D (800 IU/day).

Cardiovascular magnetic resonance imaging was used to assess various aspects of aortic structure and function, including aortic arch pulse wave velocity, aortic distensibility and dimensions, and periaortic fat.

Weight loss was greater among subjects with CR plus exercise, compared with that of patients in the exercise-only group. The degree of weight loss was not significantly different between those with moderate versus intense CR ( 8.02 kg vs. 8.98 kg).

Among the exercise-only group, researchers observed no changes in aortic stiffness. However, adding moderate CR significantly improved this measure, while intense CR did not.

Specifically, subjects in the moderate-CR group had a “robust” 21% increase in distensibility in the descending aorta (DA), and an 8% decrease in aortic arch pulse wave velocity, whereas there were no significant vascular changes in the intense-CR group.

Bests results seen in exercise plus modest CR group

“Collectively, these data suggest that combining exercise with modest CR (as opposed to more intensive CR or no CR) provides the greatest benefit for proximal aortic stiffness, while also optimizing weight loss and improvements in body composition and body fat distribution,” noted the authors in their paper.

“Our data support the growing number of studies indicating that intentional weight loss can be safe for older adults with obesity and extend our previous findings, suggesting that obesity may blunt the beneficial effects of exercise for not only cardiorespiratory fitness, but likely vascular health as well.”

William E. Kraus, MD, professor in the Department of Medicine, Division of Cardiology at Duke University Medical Center, in Durham, NC, described the study as important and interesting for several reasons.

“First, it demonstrates one can change aortic vascular function with a combined diet and exercise program, even in older, obese Americans. This implies it is never too late to make meaningful lifestyle changes that will benefit cardiovascular health,” he said. “Second, it is among an increasing number of studies demonstrating that more is not always better than less in exercise and diet lifestyle changes - and in fact the converse is true.” 

“This gives hope that more people can benefit from modest lifestyle changes - in this case following guidelines for physical activity and only a modest reduction of 250 kilocalories per day resulted in benefit,” Dr. Kraus added.

The authors of the paper and Dr. Kraus disclosed no conflicts of interest.

Small increases in daily physical activity are associated with a boost in 1-year survival in patients with heart failure and coronary disease who received an implantable cardioverter defibrillator (ICD), new research suggests.

“Our study looked at how much exercise was necessary for a better outcome in patients with prior ICD implantation and, for every 10 minutes of exercise, we saw a 1% reduction in the likelihood of death or hospitalization, which is a pretty profound impact on outcome for just a small amount of additional physical activity per day,” lead author Brett Atwater, MD, told this news organization.

“These improvements were achieved outside of a formal cardiac rehabilitation program, suggesting that the benefits of increased physical activity obtained in cardiac rehabilitation programs may also be achievable at home,” he said.

Cardiac rehabilitation (CR) programs have been shown to improve short- and long-term outcomes in patients with heart failure (HF) but continue to be underutilized, especially by women, the elderly, and minorities. Home-based CR could help overcome this limitation but the science behind it is relatively new, noted Dr. Atwater, director of electrophysiology and electrophysiology research, Inova Heart and Vascular Institute, Fairfax, Va.

As reported in Circulation Cardiovascular Quality and Outcomes, the study involved 41,731 Medicare beneficiaries (mean age, 73.5 years) who received an ICD from 2014 to 2016.

ICD heart rate and activity sensor measurements were used to establish a personalized physical activity (PA) threshold for each patient in the first 3 weeks after ICD implantation. Thereafter, the ICD logged PA when the personalized PA threshold was exceeded. The mean baseline PA level was 128.9 minutes/day.

At 3 years’ follow-up, one-quarter of the patients had died and half had been hospitalized for HF. Of the total population, only 3.2% participated in CR.

Compared with nonparticipants, CR participants were more likely to be White (91.0% versus 87.3%), male (75.5% versus 72.2%), and to have diabetes (48.8% versus 44.1%), ischemic heart disease (91.4% versus 82.1%), or congestive heart failure (90.4% versus 83.4%).

CR participants attended a median of 24 sessions, during which time daily PA increased by a mean of 9.7 minutes per day. During the same time, PA decreased by a mean of 1.0 minute per day in non-CR participants (P < .001).

PA levels remained “relatively constant” for the first 36 months of follow-up among CR participants before showing a steep decline, whereas levels gradually declined throughout follow-up among nonparticipants, with a median annual change of –4.5 min/day.

In adjusted analysis, every 10 minutes of increased daily PA was associated with a 1.1% reduced risk for death (hazard ratio, 0.989; 95% confidence interval, 0.979-0.996) and a 1% reduced risk for HF hospitalization (HR, 0.99; 95% CI, 0.986-0.995) at 1-year follow-up (P < .001).

After propensity score was used to match CR participants with nonparticipants by demographic characteristics, comorbidities, and baseline PA level, CR participants had a significantly lower risk for death at 1 year (HR, 0.76; 95% CI, 0.69-0.85). This difference in risk remained at 2- and 3-year follow-ups.

However, when the researchers further adjusted for change in PA during CR or the same time period after device implantation, no differences in mortality were found between CR participants and nonparticipants at 1 year (HR, 1.00; 95% CI, 0.82-1.21) or at 2 or 3 years.

The risk for HF hospitalization did not differ between the two groups in either propensity score model.

Unlike wearable devices, implanted devices “don’t give that type of feedback to patients regarding PA levels – only to providers – and it will be interesting to discover whether providing feedback to patients can motivate them to do more physical activity,” Dr. Atwater commented.

The team is currently enrolling patients in a follow-up trial, in which patients will be given feedback from their ICD “to move these data from an interesting observation to something that can drive outcomes,” he said.

Commenting for this news organization, Melissa Tracy, MD, Rush University Medical Center, Chicago, said the study reiterates the “profound” underutilization of CR.

“Only about 3% of patients who should have qualified for cardiac rehabilitation actually attended, which is startling considering that it has class 1A level of evidence supporting its use,” she said.

Dr. Tracy, who is also a member of the American College of Cardiology’s Prevention of Cardiovascular Disease Section Leadership Council, described the study as “another notch in the belt of positive outcomes supporting the need for cardiac rehabilitation” and emphasizing the importance of a home-based alternative.

“One of the reasons women, minorities, and older patients don’t go to cardiac rehabilitation is they have to get there, rely on someone to drive them, or they have other responsibilities – especially women, who are often primary caretakers of others,” she said. “For women and men, the pressure to get back to work and support their families means they don’t have the luxury to go to cardiac rehabilitation.”

Dr. Tracy noted that home-based CR is covered by CMS until the end of 2021. “An important take-home is for providers and patients to understand that they do have a home-based option,” she stated.

Limitations of the study are that only 24% of patients were women, only 6% were Black, and the results might not be generalizable to patients younger than 65 years, note Dr. Atwater and colleagues. Also, previous implantation might have protected the cohort from experiencing arrhythmic death, and it remains unclear if similar results would be obtained in patients without a previous ICD.

This research was funded through the unrestricted Abbott Medical-Duke Health Strategic Alliance Research Grant. Dr. Atwater receives significant research support from Boston Scientific and Abbott Medical, and modest honoraria from Abbott Medical, Medtronic, and Biotronik. Coauthor disclosures are listed in the paper. Dr. Tracy has created cardiac prevention programs with Virtual Health Partners (VHP) and owns the intellectual property and consults with VHP but receives no monetary compensation.
 

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

Small increases in daily physical activity are associated with a boost in 1-year survival in patients with heart failure and coronary disease who received an implantable cardioverter defibrillator (ICD), new research suggests.

“Our study looked at how much exercise was necessary for a better outcome in patients with prior ICD implantation and, for every 10 minutes of exercise, we saw a 1% reduction in the likelihood of death or hospitalization, which is a pretty profound impact on outcome for just a small amount of additional physical activity per day,” lead author Brett Atwater, MD, told this news organization.

“These improvements were achieved outside of a formal cardiac rehabilitation program, suggesting that the benefits of increased physical activity obtained in cardiac rehabilitation programs may also be achievable at home,” he said.

Cardiac rehabilitation (CR) programs have been shown to improve short- and long-term outcomes in patients with heart failure (HF) but continue to be underutilized, especially by women, the elderly, and minorities. Home-based CR could help overcome this limitation but the science behind it is relatively new, noted Dr. Atwater, director of electrophysiology and electrophysiology research, Inova Heart and Vascular Institute, Fairfax, Va.

As reported in Circulation Cardiovascular Quality and Outcomes, the study involved 41,731 Medicare beneficiaries (mean age, 73.5 years) who received an ICD from 2014 to 2016.

ICD heart rate and activity sensor measurements were used to establish a personalized physical activity (PA) threshold for each patient in the first 3 weeks after ICD implantation. Thereafter, the ICD logged PA when the personalized PA threshold was exceeded. The mean baseline PA level was 128.9 minutes/day.

At 3 years’ follow-up, one-quarter of the patients had died and half had been hospitalized for HF. Of the total population, only 3.2% participated in CR.

Compared with nonparticipants, CR participants were more likely to be White (91.0% versus 87.3%), male (75.5% versus 72.2%), and to have diabetes (48.8% versus 44.1%), ischemic heart disease (91.4% versus 82.1%), or congestive heart failure (90.4% versus 83.4%).

CR participants attended a median of 24 sessions, during which time daily PA increased by a mean of 9.7 minutes per day. During the same time, PA decreased by a mean of 1.0 minute per day in non-CR participants (P < .001).

PA levels remained “relatively constant” for the first 36 months of follow-up among CR participants before showing a steep decline, whereas levels gradually declined throughout follow-up among nonparticipants, with a median annual change of –4.5 min/day.

In adjusted analysis, every 10 minutes of increased daily PA was associated with a 1.1% reduced risk for death (hazard ratio, 0.989; 95% confidence interval, 0.979-0.996) and a 1% reduced risk for HF hospitalization (HR, 0.99; 95% CI, 0.986-0.995) at 1-year follow-up (P < .001).

After propensity score was used to match CR participants with nonparticipants by demographic characteristics, comorbidities, and baseline PA level, CR participants had a significantly lower risk for death at 1 year (HR, 0.76; 95% CI, 0.69-0.85). This difference in risk remained at 2- and 3-year follow-ups.

However, when the researchers further adjusted for change in PA during CR or the same time period after device implantation, no differences in mortality were found between CR participants and nonparticipants at 1 year (HR, 1.00; 95% CI, 0.82-1.21) or at 2 or 3 years.

The risk for HF hospitalization did not differ between the two groups in either propensity score model.

Unlike wearable devices, implanted devices “don’t give that type of feedback to patients regarding PA levels – only to providers – and it will be interesting to discover whether providing feedback to patients can motivate them to do more physical activity,” Dr. Atwater commented.

The team is currently enrolling patients in a follow-up trial, in which patients will be given feedback from their ICD “to move these data from an interesting observation to something that can drive outcomes,” he said.

Commenting for this news organization, Melissa Tracy, MD, Rush University Medical Center, Chicago, said the study reiterates the “profound” underutilization of CR.

“Only about 3% of patients who should have qualified for cardiac rehabilitation actually attended, which is startling considering that it has class 1A level of evidence supporting its use,” she said.

Dr. Tracy, who is also a member of the American College of Cardiology’s Prevention of Cardiovascular Disease Section Leadership Council, described the study as “another notch in the belt of positive outcomes supporting the need for cardiac rehabilitation” and emphasizing the importance of a home-based alternative.

“One of the reasons women, minorities, and older patients don’t go to cardiac rehabilitation is they have to get there, rely on someone to drive them, or they have other responsibilities – especially women, who are often primary caretakers of others,” she said. “For women and men, the pressure to get back to work and support their families means they don’t have the luxury to go to cardiac rehabilitation.”

Dr. Tracy noted that home-based CR is covered by CMS until the end of 2021. “An important take-home is for providers and patients to understand that they do have a home-based option,” she stated.

Limitations of the study are that only 24% of patients were women, only 6% were Black, and the results might not be generalizable to patients younger than 65 years, note Dr. Atwater and colleagues. Also, previous implantation might have protected the cohort from experiencing arrhythmic death, and it remains unclear if similar results would be obtained in patients without a previous ICD.

This research was funded through the unrestricted Abbott Medical-Duke Health Strategic Alliance Research Grant. Dr. Atwater receives significant research support from Boston Scientific and Abbott Medical, and modest honoraria from Abbott Medical, Medtronic, and Biotronik. Coauthor disclosures are listed in the paper. Dr. Tracy has created cardiac prevention programs with Virtual Health Partners (VHP) and owns the intellectual property and consults with VHP but receives no monetary compensation.
 

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

Small increases in daily physical activity are associated with a boost in 1-year survival in patients with heart failure and coronary disease who received an implantable cardioverter defibrillator (ICD), new research suggests.

“Our study looked at how much exercise was necessary for a better outcome in patients with prior ICD implantation and, for every 10 minutes of exercise, we saw a 1% reduction in the likelihood of death or hospitalization, which is a pretty profound impact on outcome for just a small amount of additional physical activity per day,” lead author Brett Atwater, MD, told this news organization.

“These improvements were achieved outside of a formal cardiac rehabilitation program, suggesting that the benefits of increased physical activity obtained in cardiac rehabilitation programs may also be achievable at home,” he said.

Cardiac rehabilitation (CR) programs have been shown to improve short- and long-term outcomes in patients with heart failure (HF) but continue to be underutilized, especially by women, the elderly, and minorities. Home-based CR could help overcome this limitation but the science behind it is relatively new, noted Dr. Atwater, director of electrophysiology and electrophysiology research, Inova Heart and Vascular Institute, Fairfax, Va.

As reported in Circulation Cardiovascular Quality and Outcomes, the study involved 41,731 Medicare beneficiaries (mean age, 73.5 years) who received an ICD from 2014 to 2016.

ICD heart rate and activity sensor measurements were used to establish a personalized physical activity (PA) threshold for each patient in the first 3 weeks after ICD implantation. Thereafter, the ICD logged PA when the personalized PA threshold was exceeded. The mean baseline PA level was 128.9 minutes/day.

At 3 years’ follow-up, one-quarter of the patients had died and half had been hospitalized for HF. Of the total population, only 3.2% participated in CR.

Compared with nonparticipants, CR participants were more likely to be White (91.0% versus 87.3%), male (75.5% versus 72.2%), and to have diabetes (48.8% versus 44.1%), ischemic heart disease (91.4% versus 82.1%), or congestive heart failure (90.4% versus 83.4%).

CR participants attended a median of 24 sessions, during which time daily PA increased by a mean of 9.7 minutes per day. During the same time, PA decreased by a mean of 1.0 minute per day in non-CR participants (P < .001).

PA levels remained “relatively constant” for the first 36 months of follow-up among CR participants before showing a steep decline, whereas levels gradually declined throughout follow-up among nonparticipants, with a median annual change of –4.5 min/day.

In adjusted analysis, every 10 minutes of increased daily PA was associated with a 1.1% reduced risk for death (hazard ratio, 0.989; 95% confidence interval, 0.979-0.996) and a 1% reduced risk for HF hospitalization (HR, 0.99; 95% CI, 0.986-0.995) at 1-year follow-up (P < .001).

After propensity score was used to match CR participants with nonparticipants by demographic characteristics, comorbidities, and baseline PA level, CR participants had a significantly lower risk for death at 1 year (HR, 0.76; 95% CI, 0.69-0.85). This difference in risk remained at 2- and 3-year follow-ups.

However, when the researchers further adjusted for change in PA during CR or the same time period after device implantation, no differences in mortality were found between CR participants and nonparticipants at 1 year (HR, 1.00; 95% CI, 0.82-1.21) or at 2 or 3 years.

The risk for HF hospitalization did not differ between the two groups in either propensity score model.

Unlike wearable devices, implanted devices “don’t give that type of feedback to patients regarding PA levels – only to providers – and it will be interesting to discover whether providing feedback to patients can motivate them to do more physical activity,” Dr. Atwater commented.

The team is currently enrolling patients in a follow-up trial, in which patients will be given feedback from their ICD “to move these data from an interesting observation to something that can drive outcomes,” he said.

Commenting for this news organization, Melissa Tracy, MD, Rush University Medical Center, Chicago, said the study reiterates the “profound” underutilization of CR.

“Only about 3% of patients who should have qualified for cardiac rehabilitation actually attended, which is startling considering that it has class 1A level of evidence supporting its use,” she said.

Dr. Tracy, who is also a member of the American College of Cardiology’s Prevention of Cardiovascular Disease Section Leadership Council, described the study as “another notch in the belt of positive outcomes supporting the need for cardiac rehabilitation” and emphasizing the importance of a home-based alternative.

“One of the reasons women, minorities, and older patients don’t go to cardiac rehabilitation is they have to get there, rely on someone to drive them, or they have other responsibilities – especially women, who are often primary caretakers of others,” she said. “For women and men, the pressure to get back to work and support their families means they don’t have the luxury to go to cardiac rehabilitation.”

Dr. Tracy noted that home-based CR is covered by CMS until the end of 2021. “An important take-home is for providers and patients to understand that they do have a home-based option,” she stated.

Limitations of the study are that only 24% of patients were women, only 6% were Black, and the results might not be generalizable to patients younger than 65 years, note Dr. Atwater and colleagues. Also, previous implantation might have protected the cohort from experiencing arrhythmic death, and it remains unclear if similar results would be obtained in patients without a previous ICD.

This research was funded through the unrestricted Abbott Medical-Duke Health Strategic Alliance Research Grant. Dr. Atwater receives significant research support from Boston Scientific and Abbott Medical, and modest honoraria from Abbott Medical, Medtronic, and Biotronik. Coauthor disclosures are listed in the paper. Dr. Tracy has created cardiac prevention programs with Virtual Health Partners (VHP) and owns the intellectual property and consults with VHP but receives no monetary compensation.
 

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

Today there are so many evidence-based drug therapies for heart failure with reduced ejection fraction (HFrEF) that physicians treating HF patients almost don’t know what to do them.

It’s an exciting new age that way, but to many vexingly unclear how best to merge the shiny new options with mainstay regimens based on time-honored renin-angiotensin system (RAS) inhibitors and beta-blockers.

To impart some clarity, the authors of a new HF guideline document recently took center stage at the Heart Failure Association of the European Society of Cardiology (ESC-HFA) annual meeting to preview their updated recommendations, with novel twists based on recent major trials, for the new age of HF pharmacotherapeutics.

The guideline committee considered the evidence base that existed “up until the end of March of this year,” Theresa A. McDonagh, MD, King’s College London, said during the presentation. The document “is now finalized, it’s with the publishers, and it will be presented in full with simultaneous publication at the ESC meeting” that starts August 27.

It describes a game plan, already followed by some clinicians in practice without official guidance, for initiating drugs from each of four classes in virtually all patients with HFrEF.
 

New indicated drugs, new perspective for HFrEF

Three of the drug categories are old acquaintances. Among them are the RAS inhibitors, which include angiotensin-receptor/neprilysin inhibitors, beta-blockers, and the mineralocorticoid receptor antagonists. The latter drugs are gaining new respect after having been underplayed in HF prescribing despite longstanding evidence of efficacy.

Completing the quartet of first-line HFrEF drug classes is a recent arrival to the HF arena, the sodium-glucose cotransporter 2 inhibitors.

“We now have new data and a simplified treatment algorithm for heart failure with reduced ejection fraction based on the early administration of the four major classes of drugs,” said Marco Metra, MD, University of Brescia (Italy), previewing the medical-therapy portions of the new guideline at the ESC-HFA sessions, which launched virtually and live in Florence, Italy, on July 29.

The new game plan offers a simple answer to a once-common but complex question: How and in what order are the different drug classes initiated in patients with HFrEF? In the new document, the stated goal is to get them all on board expeditiously and safely, by any means possible.

The guideline writers did not specify a sequence, preferring to leave that decision to physicians, said Dr. Metra, who stated only two guiding principles. The first is to consider the patient’s unique circumstances. The order in which the drugs are introduced might vary, depending on, for example, whether the patient has low or high blood pressure or renal dysfunction.

Second, “it is very important that we try to give all four classes of drugs to the patient in the shortest time possible, because this saves lives,” he said.

That there is no recommendation on sequencing the drugs has led some to the wrong interpretation that all should be started at once, observed coauthor Javed Butler, MD, MPH, University of Mississippi, Jackson, as a panelist during the presentation. Far from it, he said. “The doctor with the patient in front of you can make the best decision. The idea here is to get all the therapies on as soon as possible, as safely as possible.”

“The order in which they are introduced is not really important,” agreed Vijay Chopra, MD, Max Super Specialty Hospital Saket, New Delhi, another coauthor on the panel. “The important thing is that at least some dose of all the four drugs needs to be introduced in the first 4-6 weeks, and then up-titrated.”

Other medical therapy can be more tailored, Dr. Metra noted, such as loop diuretics for patients with congestion, iron for those with iron deficiency, and other drugs depending on whether there is, for example, atrial fibrillation or coronary disease.
 

Adoption of emerging definitions

The document adopts the emerging characterization of HFrEF by a left ventricular ejection fraction (LVEF) up to 40%.

And it will leverage an expanding evidence base for medication in a segment of patients once said to have HF with preserved ejection fraction (HFpEF), who had therefore lacked specific, guideline-directed medical therapies. Now, patients with an LVEF of 41%-49% will be said to have HF with mildly reduced ejection fraction (HFmrEF), a tweak to the recently introduced HF with “mid-range” LVEF that is designed to assert its nature as something to treat. The new document’s HFmrEF recommendations come with various class and level-of-evidence ratings.

That leaves HFpEF to be characterized by an LVEF of 50% in combination with structural or functional abnormalities associated with LV diastolic dysfunction or raised LV filling pressures, including raised natriuretic peptide levels.

The definitions are consistent with those proposed internationally by the ESC-HFA, the Heart Failure Society of America, and other groups in a statement published in March.
 

Expanded HFrEF med landscape

Since the 2016 ESC guideline on HF therapy, Dr. McDonagh said, “there’s been no substantial change in the evidence for many of the classical drugs that we use in heart failure. However, we had a lot of new and exciting evidence to consider,” especially in support of the SGLT2 inhibitors as one of the core medications in HFrEF.

The new data came from two controlled trials in particular. In DAPA-HF, patients with HFrEF who were initially without diabetes and who went on dapagliflozin (Farxiga, AstraZeneca) showed a 27% drop in cardiovascular (CV) death or worsening-HF events over a median of 18 months.

“That was followed up with very concordant results with empagliflozin [Jardiance, Boehringer Ingelheim/Eli Lilly] in HFrEF in the EMPEROR-Reduced trial,” Dr. McDonagh said. In that trial, comparable patients who took empagliflozin showed a 25% drop in a primary endpoint similar to that in DAPA-HF over the median 16-month follow-up.

Other HFrEF recommendations are for selected patients. They include ivabradine, already in the guidelines, for patients in sinus rhythm with an elevated resting heart rate who can’t take beta-blockers for whatever reason. But, Dr. McDonagh noted, “we had some new classes of drugs to consider as well.”

In particular, the oral soluble guanylate-cyclase receptor stimulator vericiguat (Verquvo) emerged about a year ago from the VICTORIA trial as a modest success for patients with HFrEF and a previous HF hospitalization. In the trial with more than 5,000 patients, treatment with vericiguat atop standard drug and device therapy was followed by a significant 10% drop in risk for CV death or HF hospitalization.

Available now or likely to be available in the United States, the European Union, Japan, and other countries, vericiguat is recommended in the new guideline for VICTORIA-like patients who don’t adequately respond to other indicated medications.
 

Little for HFpEF as newly defined

“Almost nothing is new” in the guidelines for HFpEF, Dr. Metra said. The document recommends screening for and treatment of any underlying disorder and comorbidities, plus diuretics for any congestion. “That’s what we have to date.”

But that evidence base might soon change. The new HFpEF recommendations could possibly be up-staged at the ESC sessions by the August 27 scheduled presentation of EMPEROR-Preserved, a randomized test of empagliflozin in HFpEF and – it could be said – HFmrEF. The trial entered patients with chronic HF and an LVEF greater than 40%.

Eli Lilly and Boehringer Ingelheim offered the world a peek at the results, which suggest the SGLT2 inhibitor had a positive impact on the primary endpoint of CV death or HF hospitalization. They announced the cursory top-line outcomes in early July as part of its regulatory obligations, noting that the trial had “met” its primary endpoint.

But many unknowns remain, including the degree of benefit and whether it varied among subgroups, and especially whether outcomes were different for HFmrEF than for HFpEF.
 

Upgrades for familiar agents

Still, HFmrEF gets noteworthy attention in the document. “For the first time, we have recommendations for these patients,” Dr. Metra said. “We already knew that diuretics are indicated for the treatment of congestion. But now, ACE inhibitors, ARBs, beta-blockers, mineralocorticoid antagonists, as well as sacubitril/valsartan, may be considered to improve outcomes in these patients.” Their upgrades in the new guidelines were based on review of trials in the CHARM program and of TOPCAT and PARAGON-HF, among others, he said.

The new document also includes “treatment algorithms based on phenotypes”; that is, comorbidities and less common HF precipitants. For example, “assessment of iron status is now mandated in all patients with heart failure,” Dr. Metra said.

AFFIRM-HF is the key trial in this arena, with its more than 1,100 iron-deficient patients with LVEF less than 50% who had been recently hospitalized for HF. A year of treatment with ferric carboxymaltose (Ferinject/Injectafer, Vifor) led to a 26% drop in risk for HF hospitalization, but without affecting mortality.

For those who are iron deficient, Dr. Metra said, “ferric carboxymaltose intravenously should be considered not only in patients with low ejection fraction and outpatients, but also in patients recently hospitalized for acute heart failure.”

The SGLT2 inhibitors are recommended in HFrEF patients with type 2 diabetes. And treatment with tafamidis (Vyndaqel, Pfizer) in patients with genetic or wild-type transthyretin cardiac amyloidosis gets a class I recommendation based on survival gains seen in the ATTR-ACT trial.

Also recommended is a full CV assessment for patients with cancer who are on cardiotoxic agents or otherwise might be at risk for chemotherapy cardiotoxicity. “Beta-blockers and ACE inhibitors should be considered in those who develop left ventricular systolic dysfunction after anticancer therapy,” Dr. Metra said.

The ongoing pandemic made its mark on the document’s genesis, as it has with most everything else. “For better or worse, we were a ‘COVID guideline,’ ” Dr. McDonagh said. The writing committee consisted of “a large task force of 31 individuals, including two patients,” and there were “only two face-to-face meetings prior to the first wave of COVID hitting Europe.”

The committee voted on each of the recommendations, “and we had to have agreement of more than 75% of the task force to assign a class of recommendation or level of evidence,” she said. “I think we did the best we could in the circumstances. We had the benefit of many discussions over Zoom, and I think at the end of the day we have achieved a consensus.”

With such a large body of participants and the 75% threshold for agreement, “you end up with perhaps a conservative guideline. But that’s not a bad thing for clinical practice, for guidelines to be conservative,” Dr. McDonagh said. “They’re mainly concerned with looking at evidence and safety.”

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

Today there are so many evidence-based drug therapies for heart failure with reduced ejection fraction (HFrEF) that physicians treating HF patients almost don’t know what to do them.

It’s an exciting new age that way, but to many vexingly unclear how best to merge the shiny new options with mainstay regimens based on time-honored renin-angiotensin system (RAS) inhibitors and beta-blockers.

To impart some clarity, the authors of a new HF guideline document recently took center stage at the Heart Failure Association of the European Society of Cardiology (ESC-HFA) annual meeting to preview their updated recommendations, with novel twists based on recent major trials, for the new age of HF pharmacotherapeutics.

The guideline committee considered the evidence base that existed “up until the end of March of this year,” Theresa A. McDonagh, MD, King’s College London, said during the presentation. The document “is now finalized, it’s with the publishers, and it will be presented in full with simultaneous publication at the ESC meeting” that starts August 27.

It describes a game plan, already followed by some clinicians in practice without official guidance, for initiating drugs from each of four classes in virtually all patients with HFrEF.
 

New indicated drugs, new perspective for HFrEF

Three of the drug categories are old acquaintances. Among them are the RAS inhibitors, which include angiotensin-receptor/neprilysin inhibitors, beta-blockers, and the mineralocorticoid receptor antagonists. The latter drugs are gaining new respect after having been underplayed in HF prescribing despite longstanding evidence of efficacy.

Completing the quartet of first-line HFrEF drug classes is a recent arrival to the HF arena, the sodium-glucose cotransporter 2 inhibitors.

“We now have new data and a simplified treatment algorithm for heart failure with reduced ejection fraction based on the early administration of the four major classes of drugs,” said Marco Metra, MD, University of Brescia (Italy), previewing the medical-therapy portions of the new guideline at the ESC-HFA sessions, which launched virtually and live in Florence, Italy, on July 29.

The new game plan offers a simple answer to a once-common but complex question: How and in what order are the different drug classes initiated in patients with HFrEF? In the new document, the stated goal is to get them all on board expeditiously and safely, by any means possible.

The guideline writers did not specify a sequence, preferring to leave that decision to physicians, said Dr. Metra, who stated only two guiding principles. The first is to consider the patient’s unique circumstances. The order in which the drugs are introduced might vary, depending on, for example, whether the patient has low or high blood pressure or renal dysfunction.

Second, “it is very important that we try to give all four classes of drugs to the patient in the shortest time possible, because this saves lives,” he said.

That there is no recommendation on sequencing the drugs has led some to the wrong interpretation that all should be started at once, observed coauthor Javed Butler, MD, MPH, University of Mississippi, Jackson, as a panelist during the presentation. Far from it, he said. “The doctor with the patient in front of you can make the best decision. The idea here is to get all the therapies on as soon as possible, as safely as possible.”

“The order in which they are introduced is not really important,” agreed Vijay Chopra, MD, Max Super Specialty Hospital Saket, New Delhi, another coauthor on the panel. “The important thing is that at least some dose of all the four drugs needs to be introduced in the first 4-6 weeks, and then up-titrated.”

Other medical therapy can be more tailored, Dr. Metra noted, such as loop diuretics for patients with congestion, iron for those with iron deficiency, and other drugs depending on whether there is, for example, atrial fibrillation or coronary disease.
 

Adoption of emerging definitions

The document adopts the emerging characterization of HFrEF by a left ventricular ejection fraction (LVEF) up to 40%.

And it will leverage an expanding evidence base for medication in a segment of patients once said to have HF with preserved ejection fraction (HFpEF), who had therefore lacked specific, guideline-directed medical therapies. Now, patients with an LVEF of 41%-49% will be said to have HF with mildly reduced ejection fraction (HFmrEF), a tweak to the recently introduced HF with “mid-range” LVEF that is designed to assert its nature as something to treat. The new document’s HFmrEF recommendations come with various class and level-of-evidence ratings.

That leaves HFpEF to be characterized by an LVEF of 50% in combination with structural or functional abnormalities associated with LV diastolic dysfunction or raised LV filling pressures, including raised natriuretic peptide levels.

The definitions are consistent with those proposed internationally by the ESC-HFA, the Heart Failure Society of America, and other groups in a statement published in March.
 

Expanded HFrEF med landscape

Since the 2016 ESC guideline on HF therapy, Dr. McDonagh said, “there’s been no substantial change in the evidence for many of the classical drugs that we use in heart failure. However, we had a lot of new and exciting evidence to consider,” especially in support of the SGLT2 inhibitors as one of the core medications in HFrEF.

The new data came from two controlled trials in particular. In DAPA-HF, patients with HFrEF who were initially without diabetes and who went on dapagliflozin (Farxiga, AstraZeneca) showed a 27% drop in cardiovascular (CV) death or worsening-HF events over a median of 18 months.

“That was followed up with very concordant results with empagliflozin [Jardiance, Boehringer Ingelheim/Eli Lilly] in HFrEF in the EMPEROR-Reduced trial,” Dr. McDonagh said. In that trial, comparable patients who took empagliflozin showed a 25% drop in a primary endpoint similar to that in DAPA-HF over the median 16-month follow-up.

Other HFrEF recommendations are for selected patients. They include ivabradine, already in the guidelines, for patients in sinus rhythm with an elevated resting heart rate who can’t take beta-blockers for whatever reason. But, Dr. McDonagh noted, “we had some new classes of drugs to consider as well.”

In particular, the oral soluble guanylate-cyclase receptor stimulator vericiguat (Verquvo) emerged about a year ago from the VICTORIA trial as a modest success for patients with HFrEF and a previous HF hospitalization. In the trial with more than 5,000 patients, treatment with vericiguat atop standard drug and device therapy was followed by a significant 10% drop in risk for CV death or HF hospitalization.

Available now or likely to be available in the United States, the European Union, Japan, and other countries, vericiguat is recommended in the new guideline for VICTORIA-like patients who don’t adequately respond to other indicated medications.
 

Little for HFpEF as newly defined

“Almost nothing is new” in the guidelines for HFpEF, Dr. Metra said. The document recommends screening for and treatment of any underlying disorder and comorbidities, plus diuretics for any congestion. “That’s what we have to date.”

But that evidence base might soon change. The new HFpEF recommendations could possibly be up-staged at the ESC sessions by the August 27 scheduled presentation of EMPEROR-Preserved, a randomized test of empagliflozin in HFpEF and – it could be said – HFmrEF. The trial entered patients with chronic HF and an LVEF greater than 40%.

Eli Lilly and Boehringer Ingelheim offered the world a peek at the results, which suggest the SGLT2 inhibitor had a positive impact on the primary endpoint of CV death or HF hospitalization. They announced the cursory top-line outcomes in early July as part of its regulatory obligations, noting that the trial had “met” its primary endpoint.

But many unknowns remain, including the degree of benefit and whether it varied among subgroups, and especially whether outcomes were different for HFmrEF than for HFpEF.
 

Upgrades for familiar agents

Still, HFmrEF gets noteworthy attention in the document. “For the first time, we have recommendations for these patients,” Dr. Metra said. “We already knew that diuretics are indicated for the treatment of congestion. But now, ACE inhibitors, ARBs, beta-blockers, mineralocorticoid antagonists, as well as sacubitril/valsartan, may be considered to improve outcomes in these patients.” Their upgrades in the new guidelines were based on review of trials in the CHARM program and of TOPCAT and PARAGON-HF, among others, he said.

The new document also includes “treatment algorithms based on phenotypes”; that is, comorbidities and less common HF precipitants. For example, “assessment of iron status is now mandated in all patients with heart failure,” Dr. Metra said.

AFFIRM-HF is the key trial in this arena, with its more than 1,100 iron-deficient patients with LVEF less than 50% who had been recently hospitalized for HF. A year of treatment with ferric carboxymaltose (Ferinject/Injectafer, Vifor) led to a 26% drop in risk for HF hospitalization, but without affecting mortality.

For those who are iron deficient, Dr. Metra said, “ferric carboxymaltose intravenously should be considered not only in patients with low ejection fraction and outpatients, but also in patients recently hospitalized for acute heart failure.”

The SGLT2 inhibitors are recommended in HFrEF patients with type 2 diabetes. And treatment with tafamidis (Vyndaqel, Pfizer) in patients with genetic or wild-type transthyretin cardiac amyloidosis gets a class I recommendation based on survival gains seen in the ATTR-ACT trial.

Also recommended is a full CV assessment for patients with cancer who are on cardiotoxic agents or otherwise might be at risk for chemotherapy cardiotoxicity. “Beta-blockers and ACE inhibitors should be considered in those who develop left ventricular systolic dysfunction after anticancer therapy,” Dr. Metra said.

The ongoing pandemic made its mark on the document’s genesis, as it has with most everything else. “For better or worse, we were a ‘COVID guideline,’ ” Dr. McDonagh said. The writing committee consisted of “a large task force of 31 individuals, including two patients,” and there were “only two face-to-face meetings prior to the first wave of COVID hitting Europe.”

The committee voted on each of the recommendations, “and we had to have agreement of more than 75% of the task force to assign a class of recommendation or level of evidence,” she said. “I think we did the best we could in the circumstances. We had the benefit of many discussions over Zoom, and I think at the end of the day we have achieved a consensus.”

With such a large body of participants and the 75% threshold for agreement, “you end up with perhaps a conservative guideline. But that’s not a bad thing for clinical practice, for guidelines to be conservative,” Dr. McDonagh said. “They’re mainly concerned with looking at evidence and safety.”

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

Today there are so many evidence-based drug therapies for heart failure with reduced ejection fraction (HFrEF) that physicians treating HF patients almost don’t know what to do them.

It’s an exciting new age that way, but to many vexingly unclear how best to merge the shiny new options with mainstay regimens based on time-honored renin-angiotensin system (RAS) inhibitors and beta-blockers.

To impart some clarity, the authors of a new HF guideline document recently took center stage at the Heart Failure Association of the European Society of Cardiology (ESC-HFA) annual meeting to preview their updated recommendations, with novel twists based on recent major trials, for the new age of HF pharmacotherapeutics.

The guideline committee considered the evidence base that existed “up until the end of March of this year,” Theresa A. McDonagh, MD, King’s College London, said during the presentation. The document “is now finalized, it’s with the publishers, and it will be presented in full with simultaneous publication at the ESC meeting” that starts August 27.

It describes a game plan, already followed by some clinicians in practice without official guidance, for initiating drugs from each of four classes in virtually all patients with HFrEF.
 

New indicated drugs, new perspective for HFrEF

Three of the drug categories are old acquaintances. Among them are the RAS inhibitors, which include angiotensin-receptor/neprilysin inhibitors, beta-blockers, and the mineralocorticoid receptor antagonists. The latter drugs are gaining new respect after having been underplayed in HF prescribing despite longstanding evidence of efficacy.

Completing the quartet of first-line HFrEF drug classes is a recent arrival to the HF arena, the sodium-glucose cotransporter 2 inhibitors.

“We now have new data and a simplified treatment algorithm for heart failure with reduced ejection fraction based on the early administration of the four major classes of drugs,” said Marco Metra, MD, University of Brescia (Italy), previewing the medical-therapy portions of the new guideline at the ESC-HFA sessions, which launched virtually and live in Florence, Italy, on July 29.

The new game plan offers a simple answer to a once-common but complex question: How and in what order are the different drug classes initiated in patients with HFrEF? In the new document, the stated goal is to get them all on board expeditiously and safely, by any means possible.

The guideline writers did not specify a sequence, preferring to leave that decision to physicians, said Dr. Metra, who stated only two guiding principles. The first is to consider the patient’s unique circumstances. The order in which the drugs are introduced might vary, depending on, for example, whether the patient has low or high blood pressure or renal dysfunction.

Second, “it is very important that we try to give all four classes of drugs to the patient in the shortest time possible, because this saves lives,” he said.

That there is no recommendation on sequencing the drugs has led some to the wrong interpretation that all should be started at once, observed coauthor Javed Butler, MD, MPH, University of Mississippi, Jackson, as a panelist during the presentation. Far from it, he said. “The doctor with the patient in front of you can make the best decision. The idea here is to get all the therapies on as soon as possible, as safely as possible.”

“The order in which they are introduced is not really important,” agreed Vijay Chopra, MD, Max Super Specialty Hospital Saket, New Delhi, another coauthor on the panel. “The important thing is that at least some dose of all the four drugs needs to be introduced in the first 4-6 weeks, and then up-titrated.”

Other medical therapy can be more tailored, Dr. Metra noted, such as loop diuretics for patients with congestion, iron for those with iron deficiency, and other drugs depending on whether there is, for example, atrial fibrillation or coronary disease.
 

Adoption of emerging definitions

The document adopts the emerging characterization of HFrEF by a left ventricular ejection fraction (LVEF) up to 40%.

And it will leverage an expanding evidence base for medication in a segment of patients once said to have HF with preserved ejection fraction (HFpEF), who had therefore lacked specific, guideline-directed medical therapies. Now, patients with an LVEF of 41%-49% will be said to have HF with mildly reduced ejection fraction (HFmrEF), a tweak to the recently introduced HF with “mid-range” LVEF that is designed to assert its nature as something to treat. The new document’s HFmrEF recommendations come with various class and level-of-evidence ratings.

That leaves HFpEF to be characterized by an LVEF of 50% in combination with structural or functional abnormalities associated with LV diastolic dysfunction or raised LV filling pressures, including raised natriuretic peptide levels.

The definitions are consistent with those proposed internationally by the ESC-HFA, the Heart Failure Society of America, and other groups in a statement published in March.
 

Expanded HFrEF med landscape

Since the 2016 ESC guideline on HF therapy, Dr. McDonagh said, “there’s been no substantial change in the evidence for many of the classical drugs that we use in heart failure. However, we had a lot of new and exciting evidence to consider,” especially in support of the SGLT2 inhibitors as one of the core medications in HFrEF.

The new data came from two controlled trials in particular. In DAPA-HF, patients with HFrEF who were initially without diabetes and who went on dapagliflozin (Farxiga, AstraZeneca) showed a 27% drop in cardiovascular (CV) death or worsening-HF events over a median of 18 months.

“That was followed up with very concordant results with empagliflozin [Jardiance, Boehringer Ingelheim/Eli Lilly] in HFrEF in the EMPEROR-Reduced trial,” Dr. McDonagh said. In that trial, comparable patients who took empagliflozin showed a 25% drop in a primary endpoint similar to that in DAPA-HF over the median 16-month follow-up.

Other HFrEF recommendations are for selected patients. They include ivabradine, already in the guidelines, for patients in sinus rhythm with an elevated resting heart rate who can’t take beta-blockers for whatever reason. But, Dr. McDonagh noted, “we had some new classes of drugs to consider as well.”

In particular, the oral soluble guanylate-cyclase receptor stimulator vericiguat (Verquvo) emerged about a year ago from the VICTORIA trial as a modest success for patients with HFrEF and a previous HF hospitalization. In the trial with more than 5,000 patients, treatment with vericiguat atop standard drug and device therapy was followed by a significant 10% drop in risk for CV death or HF hospitalization.

Available now or likely to be available in the United States, the European Union, Japan, and other countries, vericiguat is recommended in the new guideline for VICTORIA-like patients who don’t adequately respond to other indicated medications.
 

Little for HFpEF as newly defined

“Almost nothing is new” in the guidelines for HFpEF, Dr. Metra said. The document recommends screening for and treatment of any underlying disorder and comorbidities, plus diuretics for any congestion. “That’s what we have to date.”

But that evidence base might soon change. The new HFpEF recommendations could possibly be up-staged at the ESC sessions by the August 27 scheduled presentation of EMPEROR-Preserved, a randomized test of empagliflozin in HFpEF and – it could be said – HFmrEF. The trial entered patients with chronic HF and an LVEF greater than 40%.

Eli Lilly and Boehringer Ingelheim offered the world a peek at the results, which suggest the SGLT2 inhibitor had a positive impact on the primary endpoint of CV death or HF hospitalization. They announced the cursory top-line outcomes in early July as part of its regulatory obligations, noting that the trial had “met” its primary endpoint.

But many unknowns remain, including the degree of benefit and whether it varied among subgroups, and especially whether outcomes were different for HFmrEF than for HFpEF.
 

Upgrades for familiar agents

Still, HFmrEF gets noteworthy attention in the document. “For the first time, we have recommendations for these patients,” Dr. Metra said. “We already knew that diuretics are indicated for the treatment of congestion. But now, ACE inhibitors, ARBs, beta-blockers, mineralocorticoid antagonists, as well as sacubitril/valsartan, may be considered to improve outcomes in these patients.” Their upgrades in the new guidelines were based on review of trials in the CHARM program and of TOPCAT and PARAGON-HF, among others, he said.

The new document also includes “treatment algorithms based on phenotypes”; that is, comorbidities and less common HF precipitants. For example, “assessment of iron status is now mandated in all patients with heart failure,” Dr. Metra said.

AFFIRM-HF is the key trial in this arena, with its more than 1,100 iron-deficient patients with LVEF less than 50% who had been recently hospitalized for HF. A year of treatment with ferric carboxymaltose (Ferinject/Injectafer, Vifor) led to a 26% drop in risk for HF hospitalization, but without affecting mortality.

For those who are iron deficient, Dr. Metra said, “ferric carboxymaltose intravenously should be considered not only in patients with low ejection fraction and outpatients, but also in patients recently hospitalized for acute heart failure.”

The SGLT2 inhibitors are recommended in HFrEF patients with type 2 diabetes. And treatment with tafamidis (Vyndaqel, Pfizer) in patients with genetic or wild-type transthyretin cardiac amyloidosis gets a class I recommendation based on survival gains seen in the ATTR-ACT trial.

Also recommended is a full CV assessment for patients with cancer who are on cardiotoxic agents or otherwise might be at risk for chemotherapy cardiotoxicity. “Beta-blockers and ACE inhibitors should be considered in those who develop left ventricular systolic dysfunction after anticancer therapy,” Dr. Metra said.

The ongoing pandemic made its mark on the document’s genesis, as it has with most everything else. “For better or worse, we were a ‘COVID guideline,’ ” Dr. McDonagh said. The writing committee consisted of “a large task force of 31 individuals, including two patients,” and there were “only two face-to-face meetings prior to the first wave of COVID hitting Europe.”

The committee voted on each of the recommendations, “and we had to have agreement of more than 75% of the task force to assign a class of recommendation or level of evidence,” she said. “I think we did the best we could in the circumstances. We had the benefit of many discussions over Zoom, and I think at the end of the day we have achieved a consensus.”

With such a large body of participants and the 75% threshold for agreement, “you end up with perhaps a conservative guideline. But that’s not a bad thing for clinical practice, for guidelines to be conservative,” Dr. McDonagh said. “They’re mainly concerned with looking at evidence and safety.”

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

A new decision pathway for the management of hypertriglyceridemia, prompted by a large and growing body of evidence that elevated triglycerides to a targetable risk factor for atherosclerotic cardiovascular disease (ASCVD), has been issued by the American College of Cardiology.

According to the chairman of the writing committee, Salim S. Virani, MD, PhD, the recommendations amplify and update more than alter the hypertriglyceridemia treatment recommendations in the 2018 joint multisociety blood cholesterol guidelines issued in 2018.

This decision pathway, however, is focused on triglycerides alone.

“The previous guidelines included a section on strategies for addressing hypertriglyceridemia to reduce ASCVD risk, but this new decision pathway builds on the recommendations with more details and with additional information,” explained Dr. Virani, professor of medicine in the section of cardiovascular research, Baylor College of Medicine, Houston.

Within this newly published document, the definitions of hypertriglyceridemia and rationale for treatment are followed by detailed algorithms for four specific patient groups with varying triglyceride levels:

• Adults with ASCVD.
• Adults at least 40 years of age with diabetes but no ASCVD.
• Adults at least 20 years of age with no ASCVD or diabetes.
• Adults at least 20 years of age with severe hypertriglyceridemia.

“In the design of these algorithms, we made an active effort to make them suitable for use by primary care physicians as well as specialists,” said Dr. Virani. Despite “lots of boxes and arrows,” the flowcharts for each of these patient groups permit clinicians to follow the decision pathway without having to reread the text.

The common emphasis in all four algorithms is to begin by evaluating patients for secondary causes of hypertriglyceridemia, such as multifactorial chylomicronemia syndrome and other diseases associated with elevated triglycerides. The next steps, also common to all algorithms, are to optimize diet and lifestyle changes that lower triglycerides, optimize glycemic control, and optimize statin therapy.

“Although commonly recognized for their impact on LDL-C, statins also provide a 10%-30% dose-dependent reduction in triglycerides in patients with elevated levels,” the guidelines state. Statins are considered a fundamental step to secondary prevention of ASCVD regardless of triglyceride levels.

Once treatable causes or contributors to hypertriglyceridemia have been addressed, lifestyle interventions and statin therapy have been optimized, pharmacologic therapy directed specifically at control of hypertriglyceridemia “can be considered” in those at highest risk of ASCVD events, but Dr. Virani explained that this is never an early or first step in control of elevated triglycerides.

“The entire working group agreed that lifestyle interventions should be highlighted front and center before considering any other intervention,” Dr. Virani explained.

Pharmacologic therapy for hypertriglyceridemia is not ignored. Prescription omega-3 fatty acid products are preferred over nonprescription dietary supplements, which may vary in quality and purity. But these products, rather than a standalone solution, are best applied within the context of efforts to improve diet, lower body weight, and increase physical activity.

Several trials have associated ethyl ester and carboxylic acid preparations with meaningful reductions in triglycerides, but these drugs, including icosapent ethyl (IPE), are not without adverse events. In the pivotal REDUCE-IT trial, IPE was linked with an increased risk of atrial fibrillation relative to placebo.

IPE is “the best option” and the only therapy with an indication for reduction in ASCVD risk, according to Dr. Virani, but he explained that safety concerns led the authors of the new decision pathway to employ cautious language in regard to its use, suggesting that it be “considered” in high-risk patients after other methods of lowering triglycerides have been optimized.

In the algorithm for the four different risk groups, the decision pathways follow stratifications for different levels of hypertriglyceridemia (defined under fasting and nonfasting conditions) and also for specific levels of LDL cholesterol. ASCVD risk assessment is also a factor in determining the next steps along the decision pathway.

According to Michael Davidson, MD, director of the lipid clinic at the University of Chicago, the emphasis on lifestyle changes for hypertriglyceridemia and the prudent language in regard to pharmacologic therapy is appropriate.

“In light of the controversies regarding the REDUCE-IT trial, the writing committee has done a nice job with providing useful guidance regarding the utilization of icosapent ethyl in higher risk patients,” Dr. Davidson said.

Calling the ACC decision pathway “a welcome enhancement of the 2018 ACC/AHA cholesterol guidelines,” Dr. Davidson praised the way in which the limitations of the evidence regarding pharmacologic therapies were explained.

“Most importantly, this decision pathway helps clinicians appreciate that hypertriglyceridemia can be best managed with lifestyle changes and addressing potential secondary causes,” Dr. Davidson said.

Dr. Virani reports no potential conflicts of interest. Dr. Davidson reports financial relationships with multiple pharmaceutical companies including those making or pursuing therapies for control of hypertriglyceridemia.

A new decision pathway for the management of hypertriglyceridemia, prompted by a large and growing body of evidence that elevated triglycerides to a targetable risk factor for atherosclerotic cardiovascular disease (ASCVD), has been issued by the American College of Cardiology.

According to the chairman of the writing committee, Salim S. Virani, MD, PhD, the recommendations amplify and update more than alter the hypertriglyceridemia treatment recommendations in the 2018 joint multisociety blood cholesterol guidelines issued in 2018.

This decision pathway, however, is focused on triglycerides alone.

“The previous guidelines included a section on strategies for addressing hypertriglyceridemia to reduce ASCVD risk, but this new decision pathway builds on the recommendations with more details and with additional information,” explained Dr. Virani, professor of medicine in the section of cardiovascular research, Baylor College of Medicine, Houston.

Within this newly published document, the definitions of hypertriglyceridemia and rationale for treatment are followed by detailed algorithms for four specific patient groups with varying triglyceride levels:

• Adults with ASCVD.
• Adults at least 40 years of age with diabetes but no ASCVD.
• Adults at least 20 years of age with no ASCVD or diabetes.
• Adults at least 20 years of age with severe hypertriglyceridemia.

“In the design of these algorithms, we made an active effort to make them suitable for use by primary care physicians as well as specialists,” said Dr. Virani. Despite “lots of boxes and arrows,” the flowcharts for each of these patient groups permit clinicians to follow the decision pathway without having to reread the text.

The common emphasis in all four algorithms is to begin by evaluating patients for secondary causes of hypertriglyceridemia, such as multifactorial chylomicronemia syndrome and other diseases associated with elevated triglycerides. The next steps, also common to all algorithms, are to optimize diet and lifestyle changes that lower triglycerides, optimize glycemic control, and optimize statin therapy.

“Although commonly recognized for their impact on LDL-C, statins also provide a 10%-30% dose-dependent reduction in triglycerides in patients with elevated levels,” the guidelines state. Statins are considered a fundamental step to secondary prevention of ASCVD regardless of triglyceride levels.

Once treatable causes or contributors to hypertriglyceridemia have been addressed, lifestyle interventions and statin therapy have been optimized, pharmacologic therapy directed specifically at control of hypertriglyceridemia “can be considered” in those at highest risk of ASCVD events, but Dr. Virani explained that this is never an early or first step in control of elevated triglycerides.

“The entire working group agreed that lifestyle interventions should be highlighted front and center before considering any other intervention,” Dr. Virani explained.

Pharmacologic therapy for hypertriglyceridemia is not ignored. Prescription omega-3 fatty acid products are preferred over nonprescription dietary supplements, which may vary in quality and purity. But these products, rather than a standalone solution, are best applied within the context of efforts to improve diet, lower body weight, and increase physical activity.

Several trials have associated ethyl ester and carboxylic acid preparations with meaningful reductions in triglycerides, but these drugs, including icosapent ethyl (IPE), are not without adverse events. In the pivotal REDUCE-IT trial, IPE was linked with an increased risk of atrial fibrillation relative to placebo.

IPE is “the best option” and the only therapy with an indication for reduction in ASCVD risk, according to Dr. Virani, but he explained that safety concerns led the authors of the new decision pathway to employ cautious language in regard to its use, suggesting that it be “considered” in high-risk patients after other methods of lowering triglycerides have been optimized.

In the algorithm for the four different risk groups, the decision pathways follow stratifications for different levels of hypertriglyceridemia (defined under fasting and nonfasting conditions) and also for specific levels of LDL cholesterol. ASCVD risk assessment is also a factor in determining the next steps along the decision pathway.

According to Michael Davidson, MD, director of the lipid clinic at the University of Chicago, the emphasis on lifestyle changes for hypertriglyceridemia and the prudent language in regard to pharmacologic therapy is appropriate.

“In light of the controversies regarding the REDUCE-IT trial, the writing committee has done a nice job with providing useful guidance regarding the utilization of icosapent ethyl in higher risk patients,” Dr. Davidson said.

Calling the ACC decision pathway “a welcome enhancement of the 2018 ACC/AHA cholesterol guidelines,” Dr. Davidson praised the way in which the limitations of the evidence regarding pharmacologic therapies were explained.

“Most importantly, this decision pathway helps clinicians appreciate that hypertriglyceridemia can be best managed with lifestyle changes and addressing potential secondary causes,” Dr. Davidson said.

Dr. Virani reports no potential conflicts of interest. Dr. Davidson reports financial relationships with multiple pharmaceutical companies including those making or pursuing therapies for control of hypertriglyceridemia.

A new decision pathway for the management of hypertriglyceridemia, prompted by a large and growing body of evidence that elevated triglycerides to a targetable risk factor for atherosclerotic cardiovascular disease (ASCVD), has been issued by the American College of Cardiology.

According to the chairman of the writing committee, Salim S. Virani, MD, PhD, the recommendations amplify and update more than alter the hypertriglyceridemia treatment recommendations in the 2018 joint multisociety blood cholesterol guidelines issued in 2018.

This decision pathway, however, is focused on triglycerides alone.

“The previous guidelines included a section on strategies for addressing hypertriglyceridemia to reduce ASCVD risk, but this new decision pathway builds on the recommendations with more details and with additional information,” explained Dr. Virani, professor of medicine in the section of cardiovascular research, Baylor College of Medicine, Houston.

Within this newly published document, the definitions of hypertriglyceridemia and rationale for treatment are followed by detailed algorithms for four specific patient groups with varying triglyceride levels:

• Adults with ASCVD.
• Adults at least 40 years of age with diabetes but no ASCVD.
• Adults at least 20 years of age with no ASCVD or diabetes.
• Adults at least 20 years of age with severe hypertriglyceridemia.

“In the design of these algorithms, we made an active effort to make them suitable for use by primary care physicians as well as specialists,” said Dr. Virani. Despite “lots of boxes and arrows,” the flowcharts for each of these patient groups permit clinicians to follow the decision pathway without having to reread the text.

The common emphasis in all four algorithms is to begin by evaluating patients for secondary causes of hypertriglyceridemia, such as multifactorial chylomicronemia syndrome and other diseases associated with elevated triglycerides. The next steps, also common to all algorithms, are to optimize diet and lifestyle changes that lower triglycerides, optimize glycemic control, and optimize statin therapy.

“Although commonly recognized for their impact on LDL-C, statins also provide a 10%-30% dose-dependent reduction in triglycerides in patients with elevated levels,” the guidelines state. Statins are considered a fundamental step to secondary prevention of ASCVD regardless of triglyceride levels.

Once treatable causes or contributors to hypertriglyceridemia have been addressed, lifestyle interventions and statin therapy have been optimized, pharmacologic therapy directed specifically at control of hypertriglyceridemia “can be considered” in those at highest risk of ASCVD events, but Dr. Virani explained that this is never an early or first step in control of elevated triglycerides.

“The entire working group agreed that lifestyle interventions should be highlighted front and center before considering any other intervention,” Dr. Virani explained.

Pharmacologic therapy for hypertriglyceridemia is not ignored. Prescription omega-3 fatty acid products are preferred over nonprescription dietary supplements, which may vary in quality and purity. But these products, rather than a standalone solution, are best applied within the context of efforts to improve diet, lower body weight, and increase physical activity.

Several trials have associated ethyl ester and carboxylic acid preparations with meaningful reductions in triglycerides, but these drugs, including icosapent ethyl (IPE), are not without adverse events. In the pivotal REDUCE-IT trial, IPE was linked with an increased risk of atrial fibrillation relative to placebo.

IPE is “the best option” and the only therapy with an indication for reduction in ASCVD risk, according to Dr. Virani, but he explained that safety concerns led the authors of the new decision pathway to employ cautious language in regard to its use, suggesting that it be “considered” in high-risk patients after other methods of lowering triglycerides have been optimized.

In the algorithm for the four different risk groups, the decision pathways follow stratifications for different levels of hypertriglyceridemia (defined under fasting and nonfasting conditions) and also for specific levels of LDL cholesterol. ASCVD risk assessment is also a factor in determining the next steps along the decision pathway.

According to Michael Davidson, MD, director of the lipid clinic at the University of Chicago, the emphasis on lifestyle changes for hypertriglyceridemia and the prudent language in regard to pharmacologic therapy is appropriate.

“In light of the controversies regarding the REDUCE-IT trial, the writing committee has done a nice job with providing useful guidance regarding the utilization of icosapent ethyl in higher risk patients,” Dr. Davidson said.

Calling the ACC decision pathway “a welcome enhancement of the 2018 ACC/AHA cholesterol guidelines,” Dr. Davidson praised the way in which the limitations of the evidence regarding pharmacologic therapies were explained.

“Most importantly, this decision pathway helps clinicians appreciate that hypertriglyceridemia can be best managed with lifestyle changes and addressing potential secondary causes,” Dr. Davidson said.

Dr. Virani reports no potential conflicts of interest. Dr. Davidson reports financial relationships with multiple pharmaceutical companies including those making or pursuing therapies for control of hypertriglyceridemia.

In the largest comparison of angiotensin receptor blockers (ARBs) and ACE inhibitors to date, a study of nearly 2.3 million patients starting the drugs as monotherapy shows no significant differences between the two in the long-term prevention of hypertension-related cardiovascular events.

However, side effects were notably lower with ARBs.

“This is a very large, well-executed observational study that confirms that ARBs appear to have fewer side effects than ACE inhibitors, and no unexpected ARB side effects were detected,” senior author George Hripcsak, MD, professor and chair of biomedical informatics at Columbia University, New York, told this news organization.

“Despite being equally guideline-recommended first-line therapies for hypertension, these results support preferentially starting ARBs rather than ACE inhibitors when initiating treatment for hypertension for physicians and patients considering renin-angiotensin system (RAS) inhibition,” the authors added in the study, published online July 26, 2021, in the journal Hypertension.

They noted that both drug classes have been on the market a long time, with proven efficacy in hypertension and “a wide availability of inexpensive generic forms.”

They also stressed that their findings only apply to patients with hypertension for whom a RAS inhibitor would be the best choice of therapy.

Commenting on the research, George Bakris, MD, of the American Heart Association’s Comprehensive Hypertension Center at the University of Chicago, said the findings were consistent with his experience in prescribing as well as researching the two drug classes.

“I have been in practice for over 30 years and studied both classes, including head-to-head prospective trials to assess blood pressure, and found in many cases better blood pressure lowering by some ARBs and always better tolerability,” he told this news organization. “I think this study confirms and extends my thoughts between the two classes of blood pressure–lowering agents.”
 

Head-to-head comparisons of ACE inhibitors and ARBs limited to date

ACE inhibitors and ARBs each have extensive evidence supporting their roles as first-line medications in the treatment of hypertension, and each have the strongest recommendations in international guidelines.

However, ACE inhibitors are prescribed more commonly than ARBs as the first-line drug for lowering blood pressure, and head-to-head comparisons of the two are limited, with conflicting results.

For the study, Dr. Hripcsak and colleagues evaluated data on almost 3 million patients starting monotherapy with an ACE inhibitor or ARB for the first time between 1996 and 2018 in the United States, Germany, and South Korea, who had no history of heart disease or stroke.

They identified a total of 2,297,881 patients initiating ACE inhibitors and 673,938 starting ARBs. Among new users of ACE inhibitors, most received lisinopril (80%), followed by ramipril and enalapril, while most patients prescribed ARBs received losartan (45%), followed by valsartan and olmesartan.

With follow-up times ranging from about 4 months to more than 18 months, the data show no statistically significant differences between ACE inhibitors versus ARBs in the primary outcomes of acute myocardial infarction (hazard ratio, 1.11), heart failure (HR, 1.03), stroke (HR, 1.07), or composite cardiovascular events (HR, 1.06).

For secondary and safety outcomes, including an analysis of 51 possible side effects, ACE inhibitors, compared with ARBs, were associated with a significantly higher risk of angioedema (HR, 3.31; P < .01), cough (HR, 1.32; P < .01), acute pancreatitis (HR, 1.32; P = .02), gastrointestinal bleeding (HR, 1.18; P = .04), and abnormal weight loss (HR, 1.18; P = .04).

While the link between ACE inhibitors and pancreatitis has been previously reported, the association with GI bleeding may be a novel finding, with no prior studies comparing those effects in the two drug classes, the authors noted.

Despite most patients taking just a couple of drugs in either class, Dr. Hripcsak said, “we don’t expect that other drugs from those classes will have fewer differences. It is possible, of course, but that is not our expectation.”
 

Results only applicable to those starting therapy with RAS inhibitors

First author RuiJun Chen, MD, added that, importantly, the results may not apply to patients switching therapies or adding on therapy, “such as for the patient whose hypertension is not effectively controlled with one drug and requires the addition of a second medication,” he said in an interview.

“Also, the suggestion of preferentially prescribing ARBs only applies to those patients and providers intending to control blood pressure through RAS inhibition,” said Dr. Chen, an assistant professor in translational data science and informatics at Geisinger Medical Center in Danville, Pa., who was a National Library of Medicine postdoctoral fellow at Columbia University at the time of the study.

Hence, he stressed the results do not extend to other classes of recommended first-line blood pressure medications.

“Essentially, since this is an ACE inhibitor versus ARB study, we would not claim that ARBs are preferred over all other types of hypertension medications which were not studied here,” the researchers emphasize.

In addition to ARBs and ACE inhibitors, other medications recommended by the AHA/American College of Cardiology in the 2017 “Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults” for the primary treatment of hypertension include thiazide diuretics and calcium channel blockers.

The study received support from the National Library of Medicine and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health; the National Science Foundation; and the Ministries of Health & Welfare and of Trade, Industry & Energy of the Republic of Korea. Dr. Hripcsak reported receiving grants from the National Library of Medicine during the study and grants from Janssen Research outside the submitted work. Dr. Bakris reported being a consultant for Merck, KBP Biosciences, and Ionis.

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

In the largest comparison of angiotensin receptor blockers (ARBs) and ACE inhibitors to date, a study of nearly 2.3 million patients starting the drugs as monotherapy shows no significant differences between the two in the long-term prevention of hypertension-related cardiovascular events.

However, side effects were notably lower with ARBs.

“This is a very large, well-executed observational study that confirms that ARBs appear to have fewer side effects than ACE inhibitors, and no unexpected ARB side effects were detected,” senior author George Hripcsak, MD, professor and chair of biomedical informatics at Columbia University, New York, told this news organization.

“Despite being equally guideline-recommended first-line therapies for hypertension, these results support preferentially starting ARBs rather than ACE inhibitors when initiating treatment for hypertension for physicians and patients considering renin-angiotensin system (RAS) inhibition,” the authors added in the study, published online July 26, 2021, in the journal Hypertension.

They noted that both drug classes have been on the market a long time, with proven efficacy in hypertension and “a wide availability of inexpensive generic forms.”

They also stressed that their findings only apply to patients with hypertension for whom a RAS inhibitor would be the best choice of therapy.

Commenting on the research, George Bakris, MD, of the American Heart Association’s Comprehensive Hypertension Center at the University of Chicago, said the findings were consistent with his experience in prescribing as well as researching the two drug classes.

“I have been in practice for over 30 years and studied both classes, including head-to-head prospective trials to assess blood pressure, and found in many cases better blood pressure lowering by some ARBs and always better tolerability,” he told this news organization. “I think this study confirms and extends my thoughts between the two classes of blood pressure–lowering agents.”
 

Head-to-head comparisons of ACE inhibitors and ARBs limited to date

ACE inhibitors and ARBs each have extensive evidence supporting their roles as first-line medications in the treatment of hypertension, and each have the strongest recommendations in international guidelines.

However, ACE inhibitors are prescribed more commonly than ARBs as the first-line drug for lowering blood pressure, and head-to-head comparisons of the two are limited, with conflicting results.

For the study, Dr. Hripcsak and colleagues evaluated data on almost 3 million patients starting monotherapy with an ACE inhibitor or ARB for the first time between 1996 and 2018 in the United States, Germany, and South Korea, who had no history of heart disease or stroke.

They identified a total of 2,297,881 patients initiating ACE inhibitors and 673,938 starting ARBs. Among new users of ACE inhibitors, most received lisinopril (80%), followed by ramipril and enalapril, while most patients prescribed ARBs received losartan (45%), followed by valsartan and olmesartan.

With follow-up times ranging from about 4 months to more than 18 months, the data show no statistically significant differences between ACE inhibitors versus ARBs in the primary outcomes of acute myocardial infarction (hazard ratio, 1.11), heart failure (HR, 1.03), stroke (HR, 1.07), or composite cardiovascular events (HR, 1.06).

For secondary and safety outcomes, including an analysis of 51 possible side effects, ACE inhibitors, compared with ARBs, were associated with a significantly higher risk of angioedema (HR, 3.31; P < .01), cough (HR, 1.32; P < .01), acute pancreatitis (HR, 1.32; P = .02), gastrointestinal bleeding (HR, 1.18; P = .04), and abnormal weight loss (HR, 1.18; P = .04).

While the link between ACE inhibitors and pancreatitis has been previously reported, the association with GI bleeding may be a novel finding, with no prior studies comparing those effects in the two drug classes, the authors noted.

Despite most patients taking just a couple of drugs in either class, Dr. Hripcsak said, “we don’t expect that other drugs from those classes will have fewer differences. It is possible, of course, but that is not our expectation.”
 

Results only applicable to those starting therapy with RAS inhibitors

First author RuiJun Chen, MD, added that, importantly, the results may not apply to patients switching therapies or adding on therapy, “such as for the patient whose hypertension is not effectively controlled with one drug and requires the addition of a second medication,” he said in an interview.

“Also, the suggestion of preferentially prescribing ARBs only applies to those patients and providers intending to control blood pressure through RAS inhibition,” said Dr. Chen, an assistant professor in translational data science and informatics at Geisinger Medical Center in Danville, Pa., who was a National Library of Medicine postdoctoral fellow at Columbia University at the time of the study.

Hence, he stressed the results do not extend to other classes of recommended first-line blood pressure medications.

“Essentially, since this is an ACE inhibitor versus ARB study, we would not claim that ARBs are preferred over all other types of hypertension medications which were not studied here,” the researchers emphasize.

In addition to ARBs and ACE inhibitors, other medications recommended by the AHA/American College of Cardiology in the 2017 “Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults” for the primary treatment of hypertension include thiazide diuretics and calcium channel blockers.

The study received support from the National Library of Medicine and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health; the National Science Foundation; and the Ministries of Health & Welfare and of Trade, Industry & Energy of the Republic of Korea. Dr. Hripcsak reported receiving grants from the National Library of Medicine during the study and grants from Janssen Research outside the submitted work. Dr. Bakris reported being a consultant for Merck, KBP Biosciences, and Ionis.

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

In the largest comparison of angiotensin receptor blockers (ARBs) and ACE inhibitors to date, a study of nearly 2.3 million patients starting the drugs as monotherapy shows no significant differences between the two in the long-term prevention of hypertension-related cardiovascular events.

However, side effects were notably lower with ARBs.

“This is a very large, well-executed observational study that confirms that ARBs appear to have fewer side effects than ACE inhibitors, and no unexpected ARB side effects were detected,” senior author George Hripcsak, MD, professor and chair of biomedical informatics at Columbia University, New York, told this news organization.

“Despite being equally guideline-recommended first-line therapies for hypertension, these results support preferentially starting ARBs rather than ACE inhibitors when initiating treatment for hypertension for physicians and patients considering renin-angiotensin system (RAS) inhibition,” the authors added in the study, published online July 26, 2021, in the journal Hypertension.

They noted that both drug classes have been on the market a long time, with proven efficacy in hypertension and “a wide availability of inexpensive generic forms.”

They also stressed that their findings only apply to patients with hypertension for whom a RAS inhibitor would be the best choice of therapy.

Commenting on the research, George Bakris, MD, of the American Heart Association’s Comprehensive Hypertension Center at the University of Chicago, said the findings were consistent with his experience in prescribing as well as researching the two drug classes.

“I have been in practice for over 30 years and studied both classes, including head-to-head prospective trials to assess blood pressure, and found in many cases better blood pressure lowering by some ARBs and always better tolerability,” he told this news organization. “I think this study confirms and extends my thoughts between the two classes of blood pressure–lowering agents.”
 

Head-to-head comparisons of ACE inhibitors and ARBs limited to date

ACE inhibitors and ARBs each have extensive evidence supporting their roles as first-line medications in the treatment of hypertension, and each have the strongest recommendations in international guidelines.

However, ACE inhibitors are prescribed more commonly than ARBs as the first-line drug for lowering blood pressure, and head-to-head comparisons of the two are limited, with conflicting results.

For the study, Dr. Hripcsak and colleagues evaluated data on almost 3 million patients starting monotherapy with an ACE inhibitor or ARB for the first time between 1996 and 2018 in the United States, Germany, and South Korea, who had no history of heart disease or stroke.

They identified a total of 2,297,881 patients initiating ACE inhibitors and 673,938 starting ARBs. Among new users of ACE inhibitors, most received lisinopril (80%), followed by ramipril and enalapril, while most patients prescribed ARBs received losartan (45%), followed by valsartan and olmesartan.

With follow-up times ranging from about 4 months to more than 18 months, the data show no statistically significant differences between ACE inhibitors versus ARBs in the primary outcomes of acute myocardial infarction (hazard ratio, 1.11), heart failure (HR, 1.03), stroke (HR, 1.07), or composite cardiovascular events (HR, 1.06).

For secondary and safety outcomes, including an analysis of 51 possible side effects, ACE inhibitors, compared with ARBs, were associated with a significantly higher risk of angioedema (HR, 3.31; P < .01), cough (HR, 1.32; P < .01), acute pancreatitis (HR, 1.32; P = .02), gastrointestinal bleeding (HR, 1.18; P = .04), and abnormal weight loss (HR, 1.18; P = .04).

While the link between ACE inhibitors and pancreatitis has been previously reported, the association with GI bleeding may be a novel finding, with no prior studies comparing those effects in the two drug classes, the authors noted.

Despite most patients taking just a couple of drugs in either class, Dr. Hripcsak said, “we don’t expect that other drugs from those classes will have fewer differences. It is possible, of course, but that is not our expectation.”
 

Results only applicable to those starting therapy with RAS inhibitors

First author RuiJun Chen, MD, added that, importantly, the results may not apply to patients switching therapies or adding on therapy, “such as for the patient whose hypertension is not effectively controlled with one drug and requires the addition of a second medication,” he said in an interview.

“Also, the suggestion of preferentially prescribing ARBs only applies to those patients and providers intending to control blood pressure through RAS inhibition,” said Dr. Chen, an assistant professor in translational data science and informatics at Geisinger Medical Center in Danville, Pa., who was a National Library of Medicine postdoctoral fellow at Columbia University at the time of the study.

Hence, he stressed the results do not extend to other classes of recommended first-line blood pressure medications.

“Essentially, since this is an ACE inhibitor versus ARB study, we would not claim that ARBs are preferred over all other types of hypertension medications which were not studied here,” the researchers emphasize.

In addition to ARBs and ACE inhibitors, other medications recommended by the AHA/American College of Cardiology in the 2017 “Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults” for the primary treatment of hypertension include thiazide diuretics and calcium channel blockers.

The study received support from the National Library of Medicine and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health; the National Science Foundation; and the Ministries of Health & Welfare and of Trade, Industry & Energy of the Republic of Korea. Dr. Hripcsak reported receiving grants from the National Library of Medicine during the study and grants from Janssen Research outside the submitted work. Dr. Bakris reported being a consultant for Merck, KBP Biosciences, and Ionis.

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

A study from Japan suggests that a history of cardiovascular events in a spouse may elevate risk for future CV events in the other partner, with one caveat: Men in the cohort study were at increased risk if their wives had such a history, but the association was only one way. The risk of events didn’t go up for women with husbands who had previously experienced a CV event.

byryo/iStock/Getty Images Plus

The results highlight the need for clinicians to screen and possibly intervene with a primary CV prevention strategy “not only first-degree relatives but also spouses with a history of cardiovascular disease,” which is not currently part of the primary prevention guidelines, Hiroyuki Ohbe, MD, University of Tokyo, told this news organization.

In their study published online July 9 in Circulation: Cardiovascular Quality and Outcomes, Dr. Ohbe and Hideo Yasunaga, MD, PhD, of the same institution, assessed the risk of subsequent CV events in adults with a spouse who had experienced a stroke of any kind or had clinical ischemic heart disease such as angina or myocardial infarction.

Johanna Contreras, MD, director of heart failure at Mount Sinai Health System in New York, is not surprised by the finding that a wife’s CV history is linked to the CV risk in the husband.

“I see this often in my practice. When you live with someone, you also behave in a similar way as the other person,” Dr. Contreras told this news organization. “For example, couples who live together are likely to both exercise and have a healthy diet and not smoke.”

And most notably, she said, “the women are usually the ones who drive the healthy behaviors in the family; they watch what the family eats, where they eat, when they eat, and the men tend to allow the women to guide this behavior.”

Dr. Ohbe and Dr. Yasunaga agree, proposing that different results for men and women in the analysis may be because of the dependence of working-aged men on their wives for major aspects of lifestyle, such as diet and exercise. Moreover, they write, increased psychological and physical stress from taking care of a spouse with CV disease may also play a role, as caregivers often neglect their own health.

The team identified 13,759 adults in a large administrative database with no history of CV disease whose spouse had such a history at their first health checkup; they were the exposure group. The team matched each of them with up to four individuals (n = 55,027) who had no CV disease history and spouses without CV disease at their first health checkup; they were the nonexposure group.

The mean observation period was 7.9 years from the first health checkup, at which the subjects’ mean age was 56 years. During the follow-up, more people in the exposure group than the nonexposure group had a history of CV events, 0.6% versus 0.4%.

In the overall cohort, the hazard ratio for future severe CV events – heart failure hospitalization or MI – in those with spouses with a history of CV disease was 1.48 (95% confidence interval, 1.15-1.90).

When stratified by sex, men whose wives had CV disease showed a significantly increased risk of a future severe CV event (HR, 1.68; 95% CI, 1.22-2.32). But women with husbands with CV disease did not (HR, 1.22; 95% CI, 0.82-1.83).

The results of all four sensitivity analyses were similar to those of the primary analysis, both in the overall cohort and in the cohorts stratified by sex. The investigators performed multivariate survival analyses: one that excluded people whose partners had died, one that included death by any cause as an outcome, and one with propensity score matching.

Further studies are needed to confirm their observations and test whether a primary prevention strategy targeted at married couples could reduce CV events, note Dr. Ohbe and Dr. Yasunaga.

The findings have implications for everyday clinical practice, Dr. Contreras said. “When I see a patient who is married and has had a heart attack, I will insist on seeing the partner as well, and I will counsel them on working together to change their lifestyle,” she said in an interview.

“Often when you have that discussion with the couple after one has a heart attack, they quit smoking together, they go the gym together, and they get healthier together,” she said. “That’s now a very important conversation we have before they leave the hospital.”

The study was supported by grants from the Japan Ministry of Health, Ministry of Labour and Welfare, and the Ministry of Education, Culture, Sports, Science and Technology. Dr. Ohbe, Dr. Yasunaga, and Dr. Contreras have disclosed no relevant financial relationships.

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

A study from Japan suggests that a history of cardiovascular events in a spouse may elevate risk for future CV events in the other partner, with one caveat: Men in the cohort study were at increased risk if their wives had such a history, but the association was only one way. The risk of events didn’t go up for women with husbands who had previously experienced a CV event.

byryo/iStock/Getty Images Plus

The results highlight the need for clinicians to screen and possibly intervene with a primary CV prevention strategy “not only first-degree relatives but also spouses with a history of cardiovascular disease,” which is not currently part of the primary prevention guidelines, Hiroyuki Ohbe, MD, University of Tokyo, told this news organization.

In their study published online July 9 in Circulation: Cardiovascular Quality and Outcomes, Dr. Ohbe and Hideo Yasunaga, MD, PhD, of the same institution, assessed the risk of subsequent CV events in adults with a spouse who had experienced a stroke of any kind or had clinical ischemic heart disease such as angina or myocardial infarction.

Johanna Contreras, MD, director of heart failure at Mount Sinai Health System in New York, is not surprised by the finding that a wife’s CV history is linked to the CV risk in the husband.

“I see this often in my practice. When you live with someone, you also behave in a similar way as the other person,” Dr. Contreras told this news organization. “For example, couples who live together are likely to both exercise and have a healthy diet and not smoke.”

And most notably, she said, “the women are usually the ones who drive the healthy behaviors in the family; they watch what the family eats, where they eat, when they eat, and the men tend to allow the women to guide this behavior.”

Dr. Ohbe and Dr. Yasunaga agree, proposing that different results for men and women in the analysis may be because of the dependence of working-aged men on their wives for major aspects of lifestyle, such as diet and exercise. Moreover, they write, increased psychological and physical stress from taking care of a spouse with CV disease may also play a role, as caregivers often neglect their own health.

The team identified 13,759 adults in a large administrative database with no history of CV disease whose spouse had such a history at their first health checkup; they were the exposure group. The team matched each of them with up to four individuals (n = 55,027) who had no CV disease history and spouses without CV disease at their first health checkup; they were the nonexposure group.

The mean observation period was 7.9 years from the first health checkup, at which the subjects’ mean age was 56 years. During the follow-up, more people in the exposure group than the nonexposure group had a history of CV events, 0.6% versus 0.4%.

In the overall cohort, the hazard ratio for future severe CV events – heart failure hospitalization or MI – in those with spouses with a history of CV disease was 1.48 (95% confidence interval, 1.15-1.90).

When stratified by sex, men whose wives had CV disease showed a significantly increased risk of a future severe CV event (HR, 1.68; 95% CI, 1.22-2.32). But women with husbands with CV disease did not (HR, 1.22; 95% CI, 0.82-1.83).

The results of all four sensitivity analyses were similar to those of the primary analysis, both in the overall cohort and in the cohorts stratified by sex. The investigators performed multivariate survival analyses: one that excluded people whose partners had died, one that included death by any cause as an outcome, and one with propensity score matching.

Further studies are needed to confirm their observations and test whether a primary prevention strategy targeted at married couples could reduce CV events, note Dr. Ohbe and Dr. Yasunaga.

The findings have implications for everyday clinical practice, Dr. Contreras said. “When I see a patient who is married and has had a heart attack, I will insist on seeing the partner as well, and I will counsel them on working together to change their lifestyle,” she said in an interview.

“Often when you have that discussion with the couple after one has a heart attack, they quit smoking together, they go the gym together, and they get healthier together,” she said. “That’s now a very important conversation we have before they leave the hospital.”

The study was supported by grants from the Japan Ministry of Health, Ministry of Labour and Welfare, and the Ministry of Education, Culture, Sports, Science and Technology. Dr. Ohbe, Dr. Yasunaga, and Dr. Contreras have disclosed no relevant financial relationships.

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

A study from Japan suggests that a history of cardiovascular events in a spouse may elevate risk for future CV events in the other partner, with one caveat: Men in the cohort study were at increased risk if their wives had such a history, but the association was only one way. The risk of events didn’t go up for women with husbands who had previously experienced a CV event.

byryo/iStock/Getty Images Plus

The results highlight the need for clinicians to screen and possibly intervene with a primary CV prevention strategy “not only first-degree relatives but also spouses with a history of cardiovascular disease,” which is not currently part of the primary prevention guidelines, Hiroyuki Ohbe, MD, University of Tokyo, told this news organization.

In their study published online July 9 in Circulation: Cardiovascular Quality and Outcomes, Dr. Ohbe and Hideo Yasunaga, MD, PhD, of the same institution, assessed the risk of subsequent CV events in adults with a spouse who had experienced a stroke of any kind or had clinical ischemic heart disease such as angina or myocardial infarction.

Johanna Contreras, MD, director of heart failure at Mount Sinai Health System in New York, is not surprised by the finding that a wife’s CV history is linked to the CV risk in the husband.

“I see this often in my practice. When you live with someone, you also behave in a similar way as the other person,” Dr. Contreras told this news organization. “For example, couples who live together are likely to both exercise and have a healthy diet and not smoke.”

And most notably, she said, “the women are usually the ones who drive the healthy behaviors in the family; they watch what the family eats, where they eat, when they eat, and the men tend to allow the women to guide this behavior.”

Dr. Ohbe and Dr. Yasunaga agree, proposing that different results for men and women in the analysis may be because of the dependence of working-aged men on their wives for major aspects of lifestyle, such as diet and exercise. Moreover, they write, increased psychological and physical stress from taking care of a spouse with CV disease may also play a role, as caregivers often neglect their own health.

The team identified 13,759 adults in a large administrative database with no history of CV disease whose spouse had such a history at their first health checkup; they were the exposure group. The team matched each of them with up to four individuals (n = 55,027) who had no CV disease history and spouses without CV disease at their first health checkup; they were the nonexposure group.

The mean observation period was 7.9 years from the first health checkup, at which the subjects’ mean age was 56 years. During the follow-up, more people in the exposure group than the nonexposure group had a history of CV events, 0.6% versus 0.4%.

In the overall cohort, the hazard ratio for future severe CV events – heart failure hospitalization or MI – in those with spouses with a history of CV disease was 1.48 (95% confidence interval, 1.15-1.90).

When stratified by sex, men whose wives had CV disease showed a significantly increased risk of a future severe CV event (HR, 1.68; 95% CI, 1.22-2.32). But women with husbands with CV disease did not (HR, 1.22; 95% CI, 0.82-1.83).

The results of all four sensitivity analyses were similar to those of the primary analysis, both in the overall cohort and in the cohorts stratified by sex. The investigators performed multivariate survival analyses: one that excluded people whose partners had died, one that included death by any cause as an outcome, and one with propensity score matching.

Further studies are needed to confirm their observations and test whether a primary prevention strategy targeted at married couples could reduce CV events, note Dr. Ohbe and Dr. Yasunaga.

The findings have implications for everyday clinical practice, Dr. Contreras said. “When I see a patient who is married and has had a heart attack, I will insist on seeing the partner as well, and I will counsel them on working together to change their lifestyle,” she said in an interview.

“Often when you have that discussion with the couple after one has a heart attack, they quit smoking together, they go the gym together, and they get healthier together,” she said. “That’s now a very important conversation we have before they leave the hospital.”

The study was supported by grants from the Japan Ministry of Health, Ministry of Labour and Welfare, and the Ministry of Education, Culture, Sports, Science and Technology. Dr. Ohbe, Dr. Yasunaga, and Dr. Contreras have disclosed no relevant financial relationships.

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

Medicare Part D spending for oral anticoagulants has risen by almost 1,600% since 2011, while the number of users has increased by just 95%, according to a new study.

In 2011, the year after the first direct oral anticoagulant (DOACs) was approved, Medicare Part D spent $0.44 billion on all oral anticoagulants. By 2019, when there a total of four DOACs on the market, spending was $7.38 billion, an increase of 1,577%, Aaron Troy, MD, MPH, and Timothy S. Anderson, MD, MAS, said in JAMA Health Forum.

rfranki@mdedge.com

Medicare Part D spending for oral anticoagulants has risen by almost 1,600% since 2011, while the number of users has increased by just 95%, according to a new study.

In 2011, the year after the first direct oral anticoagulant (DOACs) was approved, Medicare Part D spent $0.44 billion on all oral anticoagulants. By 2019, when there a total of four DOACs on the market, spending was $7.38 billion, an increase of 1,577%, Aaron Troy, MD, MPH, and Timothy S. Anderson, MD, MAS, said in JAMA Health Forum.

rfranki@mdedge.com

Medicare Part D spending for oral anticoagulants has risen by almost 1,600% since 2011, while the number of users has increased by just 95%, according to a new study.

In 2011, the year after the first direct oral anticoagulant (DOACs) was approved, Medicare Part D spent $0.44 billion on all oral anticoagulants. By 2019, when there a total of four DOACs on the market, spending was $7.38 billion, an increase of 1,577%, Aaron Troy, MD, MPH, and Timothy S. Anderson, MD, MAS, said in JAMA Health Forum.

rfranki@mdedge.com

In type 2 diabetes (T2D), a greater degree of hyperlipidemia and hypertension, although not hyperglycemia, was associated with measurable cognitive impairment even among patients with only a 4-year mean disease duration, according to a substudy of the GRADE trial.

The association of these cardiovascular (CV) risk factors with impairments in cognition has been reported before, but the findings are notable because the mean duration of T2D was short in a relatively healthy study population, reported a multicenter team of investigators.

The relative impairments in cognitive function “may not be clinically significant given the very small size of the differences,” conceded the authors of this study, led by José A. Luchsinger, MD, but they are consistent with previous reports of the same association in older patients with a longer duration of diabetes. In other words, the data suggest the risk of cognitive loss from CV risk factors in T2D patients begins early.

“A potential explanation for the small differences, compared with those previously reported, is that the GRADE cohort is relatively young with a healthier cardiovascular profile and shorter diabetes duration compared with other studies,” reported the investigators, whose results were published online July 20, 2021, in Diabetes Care.
 

99% complete cognitive assessments

In the GRADE (Glycemia Reduction Approaches in Diabetes: Comparative Effectiveness) trial, 5,018 (99.4%) of the 5,047 enrolled patients completed a battery of cognitive assessments at baseline. Patients were excluded from this study if they had any major CV event in the previous year, if they had T2D for more than 10 years, if they had significant renal impairment, and if they had any history of stage 3 or greater heart failure. Their mean age was 56.7 years.

By cross-sectional analysis, cognitive evaluations, including the Digit Symbol Substitution Test (DSST) and the Spanish English Verbal Learning Test, were evaluated in relation to baseline LDL cholesterol levels, systolic and diastolic blood pressure, hemoglobin A1c, and statin use.

Unlike previous studies in T2D patients, no relationship was observed between cognitive function and A1c level at baseline. However, LDL cholesterol greater than 100 mg/dL was associated with cognitive impairment as measured with the DSST after adjustment for age, sex, education, and general health. The mean difference relative to LDL cholesterol below 70 mg/dL was only 1.8 points, but this was highly significant (P < .001).

Similarly, significant but modest cognitive impairment on DSST score after adjustment for variables were seen for those with a systolic BP between 120 mg and <140 mg relative to either <120 mm Hg or at least 140 mm Hg (P = .014). The same was seen for diastolic BPs of 80 to <90 when compared with either <80 mm Hg or to 90 mm Hg or higher (P = .01).

For those taking statins versus no statins at baseline, there was a 1.4-point mean advantage in DSST score after adjusting for variables (P < .001).

Modest cognitive impairments recorded

Again, the absolute mean differences in the DSST cognitive scores, despite their statistical significance, were modest, according to the authors. In general, the mean difference was rarely greater than 2.0 points and often 1.0 point or less. The authors acknowledged that these changes are of an uncertain clinical significance, but they considered the findings consistent with the association of CV risk factors with cognitive deficits in older T2DM patients or T2DM patients with longer duration of disease.

One difference between this GRADE substudy and previous studies was the lack of an association between cognitive impairment and hyperglycemia. In the ACCORD trial for example, increased levels of blood glycemia were associated with lower performance on numerous tests of cognitive function.

In the Diabetes Control and Complications Trial (DCCT), poorer glycemic control was related to poorer performance on tests of executive function.

Both of those studies also linked hypertension and hyperlipidemia with cognitive deficits, but given that patients in ACCORD had T2DM of substantially longer duration and those in DCCT were older, “it seems reasonable to speculate that, in patients with diabetes duration of less than 10 years, the association between hyperglycemia and cognitive performance may not yet be evident,” the GRADE authors reported.
 

GRADE trial compares drugs in four classes

The GRADE trial was conducted to compare four classes of T2D therapies for long-term glycemic control as expressed by A1c control over time. The results of the trial, presented recently at the 2021 annual scientific sessions of the American Diabetes Association, found that insulin glargine and the glucagonlike peptide–1 receptor agonist liraglutide performed best on the primary endpoint of maintaining A1c below 7.0%. Both performed significantly better than the sulfonylurea glimepiride and the dipeptidyl peptidase–4 inhibitor sitagliptin.

This substudy of baseline cognitive function in the relatively large GRADE trial provided a unique opportunity to evaluate the impact of CV risk factors in patients with T2D of relatively short duration.

While the data support the adverse impact of inadequately controlled modifiable risk factors on cognitive function in T2D patients, David R. Matthews, DPhil, BM, BCh, emeritus professor of diabetes medicine at the University of Oxford (England), noted that the association was weak and advised a cautious interpretation.

“The effect size is very small indeed. The data are found as a subset of multiple testing,” he said in an interview. He suggested the associations might be the result of “data farming,” and he emphasized that the relationships between these risk factors and cognitive deficits are associations that do not imply causation.

Nevertheless, and despite their unclear clinical implications, Dr. Matthews said that these data might still have a message.

“It is another reminder that for many reasons we all need to be alert to the need for lowering hyperlipidemia and hypertension to normal levels – the benefits may not just be limited to cardiovascular outcome,” Dr. Matthews stated.

The lead author of the study, Dr. Luchsinger, also cautioned against overinterpreting the data.

While the data show that “lipid and blood pressure control within recommended guidelines are associated with marginally better cognitive function in patients with type 2 diabetes of less than 5 years duration on average,” he added that “the study is limited by its cross-sectional nature.”

He indicated that further analysis will be helpful in assessing the implications.

“Longitudinal analyses of the same group of individuals will be conducted next year,” noted Dr. Luchsinger, associate professor of medicine and epidemiology, Columbia University Medical Center, New York.

Dr. Luchsinger reported financial relationships with vTv therapeutics. Dr. Matthews reported no potential conflicts of interest.

In type 2 diabetes (T2D), a greater degree of hyperlipidemia and hypertension, although not hyperglycemia, was associated with measurable cognitive impairment even among patients with only a 4-year mean disease duration, according to a substudy of the GRADE trial.

The association of these cardiovascular (CV) risk factors with impairments in cognition has been reported before, but the findings are notable because the mean duration of T2D was short in a relatively healthy study population, reported a multicenter team of investigators.

The relative impairments in cognitive function “may not be clinically significant given the very small size of the differences,” conceded the authors of this study, led by José A. Luchsinger, MD, but they are consistent with previous reports of the same association in older patients with a longer duration of diabetes. In other words, the data suggest the risk of cognitive loss from CV risk factors in T2D patients begins early.

“A potential explanation for the small differences, compared with those previously reported, is that the GRADE cohort is relatively young with a healthier cardiovascular profile and shorter diabetes duration compared with other studies,” reported the investigators, whose results were published online July 20, 2021, in Diabetes Care.
 

99% complete cognitive assessments

In the GRADE (Glycemia Reduction Approaches in Diabetes: Comparative Effectiveness) trial, 5,018 (99.4%) of the 5,047 enrolled patients completed a battery of cognitive assessments at baseline. Patients were excluded from this study if they had any major CV event in the previous year, if they had T2D for more than 10 years, if they had significant renal impairment, and if they had any history of stage 3 or greater heart failure. Their mean age was 56.7 years.

By cross-sectional analysis, cognitive evaluations, including the Digit Symbol Substitution Test (DSST) and the Spanish English Verbal Learning Test, were evaluated in relation to baseline LDL cholesterol levels, systolic and diastolic blood pressure, hemoglobin A1c, and statin use.

Unlike previous studies in T2D patients, no relationship was observed between cognitive function and A1c level at baseline. However, LDL cholesterol greater than 100 mg/dL was associated with cognitive impairment as measured with the DSST after adjustment for age, sex, education, and general health. The mean difference relative to LDL cholesterol below 70 mg/dL was only 1.8 points, but this was highly significant (P < .001).

Similarly, significant but modest cognitive impairment on DSST score after adjustment for variables were seen for those with a systolic BP between 120 mg and <140 mg relative to either <120 mm Hg or at least 140 mm Hg (P = .014). The same was seen for diastolic BPs of 80 to <90 when compared with either <80 mm Hg or to 90 mm Hg or higher (P = .01).

For those taking statins versus no statins at baseline, there was a 1.4-point mean advantage in DSST score after adjusting for variables (P < .001).

Modest cognitive impairments recorded

Again, the absolute mean differences in the DSST cognitive scores, despite their statistical significance, were modest, according to the authors. In general, the mean difference was rarely greater than 2.0 points and often 1.0 point or less. The authors acknowledged that these changes are of an uncertain clinical significance, but they considered the findings consistent with the association of CV risk factors with cognitive deficits in older T2DM patients or T2DM patients with longer duration of disease.

One difference between this GRADE substudy and previous studies was the lack of an association between cognitive impairment and hyperglycemia. In the ACCORD trial for example, increased levels of blood glycemia were associated with lower performance on numerous tests of cognitive function.

In the Diabetes Control and Complications Trial (DCCT), poorer glycemic control was related to poorer performance on tests of executive function.

Both of those studies also linked hypertension and hyperlipidemia with cognitive deficits, but given that patients in ACCORD had T2DM of substantially longer duration and those in DCCT were older, “it seems reasonable to speculate that, in patients with diabetes duration of less than 10 years, the association between hyperglycemia and cognitive performance may not yet be evident,” the GRADE authors reported.
 

GRADE trial compares drugs in four classes

The GRADE trial was conducted to compare four classes of T2D therapies for long-term glycemic control as expressed by A1c control over time. The results of the trial, presented recently at the 2021 annual scientific sessions of the American Diabetes Association, found that insulin glargine and the glucagonlike peptide–1 receptor agonist liraglutide performed best on the primary endpoint of maintaining A1c below 7.0%. Both performed significantly better than the sulfonylurea glimepiride and the dipeptidyl peptidase–4 inhibitor sitagliptin.

This substudy of baseline cognitive function in the relatively large GRADE trial provided a unique opportunity to evaluate the impact of CV risk factors in patients with T2D of relatively short duration.

While the data support the adverse impact of inadequately controlled modifiable risk factors on cognitive function in T2D patients, David R. Matthews, DPhil, BM, BCh, emeritus professor of diabetes medicine at the University of Oxford (England), noted that the association was weak and advised a cautious interpretation.

“The effect size is very small indeed. The data are found as a subset of multiple testing,” he said in an interview. He suggested the associations might be the result of “data farming,” and he emphasized that the relationships between these risk factors and cognitive deficits are associations that do not imply causation.

Nevertheless, and despite their unclear clinical implications, Dr. Matthews said that these data might still have a message.

“It is another reminder that for many reasons we all need to be alert to the need for lowering hyperlipidemia and hypertension to normal levels – the benefits may not just be limited to cardiovascular outcome,” Dr. Matthews stated.

The lead author of the study, Dr. Luchsinger, also cautioned against overinterpreting the data.

While the data show that “lipid and blood pressure control within recommended guidelines are associated with marginally better cognitive function in patients with type 2 diabetes of less than 5 years duration on average,” he added that “the study is limited by its cross-sectional nature.”

He indicated that further analysis will be helpful in assessing the implications.

“Longitudinal analyses of the same group of individuals will be conducted next year,” noted Dr. Luchsinger, associate professor of medicine and epidemiology, Columbia University Medical Center, New York.

Dr. Luchsinger reported financial relationships with vTv therapeutics. Dr. Matthews reported no potential conflicts of interest.

In type 2 diabetes (T2D), a greater degree of hyperlipidemia and hypertension, although not hyperglycemia, was associated with measurable cognitive impairment even among patients with only a 4-year mean disease duration, according to a substudy of the GRADE trial.

The association of these cardiovascular (CV) risk factors with impairments in cognition has been reported before, but the findings are notable because the mean duration of T2D was short in a relatively healthy study population, reported a multicenter team of investigators.

The relative impairments in cognitive function “may not be clinically significant given the very small size of the differences,” conceded the authors of this study, led by José A. Luchsinger, MD, but they are consistent with previous reports of the same association in older patients with a longer duration of diabetes. In other words, the data suggest the risk of cognitive loss from CV risk factors in T2D patients begins early.

“A potential explanation for the small differences, compared with those previously reported, is that the GRADE cohort is relatively young with a healthier cardiovascular profile and shorter diabetes duration compared with other studies,” reported the investigators, whose results were published online July 20, 2021, in Diabetes Care.
 

99% complete cognitive assessments

In the GRADE (Glycemia Reduction Approaches in Diabetes: Comparative Effectiveness) trial, 5,018 (99.4%) of the 5,047 enrolled patients completed a battery of cognitive assessments at baseline. Patients were excluded from this study if they had any major CV event in the previous year, if they had T2D for more than 10 years, if they had significant renal impairment, and if they had any history of stage 3 or greater heart failure. Their mean age was 56.7 years.

By cross-sectional analysis, cognitive evaluations, including the Digit Symbol Substitution Test (DSST) and the Spanish English Verbal Learning Test, were evaluated in relation to baseline LDL cholesterol levels, systolic and diastolic blood pressure, hemoglobin A1c, and statin use.

Unlike previous studies in T2D patients, no relationship was observed between cognitive function and A1c level at baseline. However, LDL cholesterol greater than 100 mg/dL was associated with cognitive impairment as measured with the DSST after adjustment for age, sex, education, and general health. The mean difference relative to LDL cholesterol below 70 mg/dL was only 1.8 points, but this was highly significant (P < .001).

Similarly, significant but modest cognitive impairment on DSST score after adjustment for variables were seen for those with a systolic BP between 120 mg and <140 mg relative to either <120 mm Hg or at least 140 mm Hg (P = .014). The same was seen for diastolic BPs of 80 to <90 when compared with either <80 mm Hg or to 90 mm Hg or higher (P = .01).

For those taking statins versus no statins at baseline, there was a 1.4-point mean advantage in DSST score after adjusting for variables (P < .001).

Modest cognitive impairments recorded

Again, the absolute mean differences in the DSST cognitive scores, despite their statistical significance, were modest, according to the authors. In general, the mean difference was rarely greater than 2.0 points and often 1.0 point or less. The authors acknowledged that these changes are of an uncertain clinical significance, but they considered the findings consistent with the association of CV risk factors with cognitive deficits in older T2DM patients or T2DM patients with longer duration of disease.

One difference between this GRADE substudy and previous studies was the lack of an association between cognitive impairment and hyperglycemia. In the ACCORD trial for example, increased levels of blood glycemia were associated with lower performance on numerous tests of cognitive function.

In the Diabetes Control and Complications Trial (DCCT), poorer glycemic control was related to poorer performance on tests of executive function.

Both of those studies also linked hypertension and hyperlipidemia with cognitive deficits, but given that patients in ACCORD had T2DM of substantially longer duration and those in DCCT were older, “it seems reasonable to speculate that, in patients with diabetes duration of less than 10 years, the association between hyperglycemia and cognitive performance may not yet be evident,” the GRADE authors reported.
 

GRADE trial compares drugs in four classes

The GRADE trial was conducted to compare four classes of T2D therapies for long-term glycemic control as expressed by A1c control over time. The results of the trial, presented recently at the 2021 annual scientific sessions of the American Diabetes Association, found that insulin glargine and the glucagonlike peptide–1 receptor agonist liraglutide performed best on the primary endpoint of maintaining A1c below 7.0%. Both performed significantly better than the sulfonylurea glimepiride and the dipeptidyl peptidase–4 inhibitor sitagliptin.

This substudy of baseline cognitive function in the relatively large GRADE trial provided a unique opportunity to evaluate the impact of CV risk factors in patients with T2D of relatively short duration.

While the data support the adverse impact of inadequately controlled modifiable risk factors on cognitive function in T2D patients, David R. Matthews, DPhil, BM, BCh, emeritus professor of diabetes medicine at the University of Oxford (England), noted that the association was weak and advised a cautious interpretation.

“The effect size is very small indeed. The data are found as a subset of multiple testing,” he said in an interview. He suggested the associations might be the result of “data farming,” and he emphasized that the relationships between these risk factors and cognitive deficits are associations that do not imply causation.

Nevertheless, and despite their unclear clinical implications, Dr. Matthews said that these data might still have a message.

“It is another reminder that for many reasons we all need to be alert to the need for lowering hyperlipidemia and hypertension to normal levels – the benefits may not just be limited to cardiovascular outcome,” Dr. Matthews stated.

The lead author of the study, Dr. Luchsinger, also cautioned against overinterpreting the data.

While the data show that “lipid and blood pressure control within recommended guidelines are associated with marginally better cognitive function in patients with type 2 diabetes of less than 5 years duration on average,” he added that “the study is limited by its cross-sectional nature.”

He indicated that further analysis will be helpful in assessing the implications.

“Longitudinal analyses of the same group of individuals will be conducted next year,” noted Dr. Luchsinger, associate professor of medicine and epidemiology, Columbia University Medical Center, New York.

Dr. Luchsinger reported financial relationships with vTv therapeutics. Dr. Matthews reported no potential conflicts of interest.

The longer a person has diabetes, the greater their risk for also developing heart failure, according to an analysis of nearly 10,000 U.S. adults followed for a median of close to 23 years.

In a multivariable analysis the rate of incident heart failure increased steadily and significantly as diabetes duration increased. Among the 168 study subjects (2% of the total study group) who had diabetes for at least 15 years, the subsequent incidence of heart failure was nearly threefold higher than among the 4,802 subjects (49%) who never had diabetes or prediabetes, reported Justin B. Echouffo-Tcheugui, MD, PhD, and coauthors in an article published in JACC Heart Failure.

People with prediabetes (32% of the study population) had a significant but modest increased rate of incident heart failure that was 16% higher than in control subjects who never developed diabetes. People with diabetes for durations of 0-4.9 years, 5.0-9.9 years, or 10-14.9 years, had steadily increasing relative incident heart failure rates of 29%, 97%, and 210%, respectively, compared with controls, reported Dr. Echouffo-Tcheugui, an endocrinologist at Johns Hopkins Medicine in Baltimore.

Similar rates of HFrEF and HFpEF

Among all 1,841 people in the dataset with diabetes for any length of time each additional 5 years of the disorder linked with a significant, relative 17% increase in the rate of incident heart failure. Incidence of heart failure rose even more sharply with added duration among those with a hemoglobin A1c of 7% or greater, compared with those with better glycemic control. And the rate of incident heart failure with reduced ejection fraction (HFrEF) roughly matched the rate of incident heart failure with preserved ejection fraction (HFpEF).

The study dataset included 9,734 adults enrolled into the Atherosclerosis Risk in Communities (ARIC) study, and during a median follow-up of 22.5 years they had nearly 2,000 episodes of either hospitalization or death secondary to incident heart failure. This included 617 (31%) events involving HFpEF, 495 events (25%) involving HFrEF, and 876 unclassified heart failure events.

The cohort averaged 63 years of age; 58% were women, 23% were Black, and 77% were White (the study design excluded people with other racial and ethnic backgrounds). The study design also excluded people with a history of heart failure or coronary artery disease, as well as those diagnosed with diabetes prior to age 18 resulting in a study group that presumably mostly had type 2 diabetes when diabetes was present. The report provided no data on the specific numbers of patients with type 1 or type 2 diabetes.

“It’s not surprising that a longer duration of diabetes is associated with heart failure, but the etiology remains problematic,” commented Robert H. Eckel, MD, an endocrinologist at the University of Colorado at Denver, Aurora. “The impact of diabetes on incident heart failure is not well know, particularly duration of diabetes,” although disorders often found in patients with diabetes, such as hypertension and diabetic cardiomyopathy, likely have roles in causing heart failure, he said.
 

Diabetes duration may signal need for an SGLT2 inhibitor

“With emerging novel treatments like the SGLT2 [sodium-glucose cotransporter 2] inhibitors for preventing heart failure hospitalizations and deaths in patients with type 2 diabetes, this is a timely analysis,” Dr. Eckel said in an interview.

“There is no question that with increased duration of type 2 diabetes” the need for an agent from the SGLT2-inhibitor class increases. Although, because of the proven protection these drugs give against heart failure events and progression of chronic kidney disease, treatment with this drug class should start early in patients with type 2 diabetes, he added.

Dr. Echouffo-Tcheugui and his coauthors agreed, citing two important clinical take-aways from their findings:

First, interventions that delay the onset of diabetes may potentially reduce incident heart failure; second, patients with diabetes might benefit from cardioprotective treatments such as SGLT2 inhibitors, the report said.

“Our observations suggest the potential prognostic relevance of diabetes duration in assessing heart failure,” the authors wrote. Integrating diabetes duration into heart failure risk estimation in people with diabetes “could help refine the selection of high-risk individuals who may derive the greatest absolute benefit from aggressive cardioprotective therapies such as SGLT2 inhibitors.”

The analysis also identified several other demographic and clinical factors that influenced the relative effect of diabetes duration. Longer duration was linked with higher rates of incident heart failure in women compared with men, in Blacks compared with Whites, in people younger than 65 compared with older people, in people with an A1c of 7% or higher, and in those with a body mass index of 30 kg/m² or greater.

The ARIC study and the analyses run by Dr. Echouffo-Tcheugui and his coauthors received no commercial funding. Dr. Echouffo-Tcheugui and Dr. Eckel had no relevant disclosures.

mzoler@mdedge.com

The longer a person has diabetes, the greater their risk for also developing heart failure, according to an analysis of nearly 10,000 U.S. adults followed for a median of close to 23 years.

In a multivariable analysis the rate of incident heart failure increased steadily and significantly as diabetes duration increased. Among the 168 study subjects (2% of the total study group) who had diabetes for at least 15 years, the subsequent incidence of heart failure was nearly threefold higher than among the 4,802 subjects (49%) who never had diabetes or prediabetes, reported Justin B. Echouffo-Tcheugui, MD, PhD, and coauthors in an article published in JACC Heart Failure.

People with prediabetes (32% of the study population) had a significant but modest increased rate of incident heart failure that was 16% higher than in control subjects who never developed diabetes. People with diabetes for durations of 0-4.9 years, 5.0-9.9 years, or 10-14.9 years, had steadily increasing relative incident heart failure rates of 29%, 97%, and 210%, respectively, compared with controls, reported Dr. Echouffo-Tcheugui, an endocrinologist at Johns Hopkins Medicine in Baltimore.

Similar rates of HFrEF and HFpEF

Among all 1,841 people in the dataset with diabetes for any length of time each additional 5 years of the disorder linked with a significant, relative 17% increase in the rate of incident heart failure. Incidence of heart failure rose even more sharply with added duration among those with a hemoglobin A1c of 7% or greater, compared with those with better glycemic control. And the rate of incident heart failure with reduced ejection fraction (HFrEF) roughly matched the rate of incident heart failure with preserved ejection fraction (HFpEF).

The study dataset included 9,734 adults enrolled into the Atherosclerosis Risk in Communities (ARIC) study, and during a median follow-up of 22.5 years they had nearly 2,000 episodes of either hospitalization or death secondary to incident heart failure. This included 617 (31%) events involving HFpEF, 495 events (25%) involving HFrEF, and 876 unclassified heart failure events.

The cohort averaged 63 years of age; 58% were women, 23% were Black, and 77% were White (the study design excluded people with other racial and ethnic backgrounds). The study design also excluded people with a history of heart failure or coronary artery disease, as well as those diagnosed with diabetes prior to age 18 resulting in a study group that presumably mostly had type 2 diabetes when diabetes was present. The report provided no data on the specific numbers of patients with type 1 or type 2 diabetes.

“It’s not surprising that a longer duration of diabetes is associated with heart failure, but the etiology remains problematic,” commented Robert H. Eckel, MD, an endocrinologist at the University of Colorado at Denver, Aurora. “The impact of diabetes on incident heart failure is not well know, particularly duration of diabetes,” although disorders often found in patients with diabetes, such as hypertension and diabetic cardiomyopathy, likely have roles in causing heart failure, he said.
 

Diabetes duration may signal need for an SGLT2 inhibitor

“With emerging novel treatments like the SGLT2 [sodium-glucose cotransporter 2] inhibitors for preventing heart failure hospitalizations and deaths in patients with type 2 diabetes, this is a timely analysis,” Dr. Eckel said in an interview.

“There is no question that with increased duration of type 2 diabetes” the need for an agent from the SGLT2-inhibitor class increases. Although, because of the proven protection these drugs give against heart failure events and progression of chronic kidney disease, treatment with this drug class should start early in patients with type 2 diabetes, he added.

Dr. Echouffo-Tcheugui and his coauthors agreed, citing two important clinical take-aways from their findings:

First, interventions that delay the onset of diabetes may potentially reduce incident heart failure; second, patients with diabetes might benefit from cardioprotective treatments such as SGLT2 inhibitors, the report said.

“Our observations suggest the potential prognostic relevance of diabetes duration in assessing heart failure,” the authors wrote. Integrating diabetes duration into heart failure risk estimation in people with diabetes “could help refine the selection of high-risk individuals who may derive the greatest absolute benefit from aggressive cardioprotective therapies such as SGLT2 inhibitors.”

The analysis also identified several other demographic and clinical factors that influenced the relative effect of diabetes duration. Longer duration was linked with higher rates of incident heart failure in women compared with men, in Blacks compared with Whites, in people younger than 65 compared with older people, in people with an A1c of 7% or higher, and in those with a body mass index of 30 kg/m² or greater.

The ARIC study and the analyses run by Dr. Echouffo-Tcheugui and his coauthors received no commercial funding. Dr. Echouffo-Tcheugui and Dr. Eckel had no relevant disclosures.

mzoler@mdedge.com

The longer a person has diabetes, the greater their risk for also developing heart failure, according to an analysis of nearly 10,000 U.S. adults followed for a median of close to 23 years.

In a multivariable analysis the rate of incident heart failure increased steadily and significantly as diabetes duration increased. Among the 168 study subjects (2% of the total study group) who had diabetes for at least 15 years, the subsequent incidence of heart failure was nearly threefold higher than among the 4,802 subjects (49%) who never had diabetes or prediabetes, reported Justin B. Echouffo-Tcheugui, MD, PhD, and coauthors in an article published in JACC Heart Failure.

People with prediabetes (32% of the study population) had a significant but modest increased rate of incident heart failure that was 16% higher than in control subjects who never developed diabetes. People with diabetes for durations of 0-4.9 years, 5.0-9.9 years, or 10-14.9 years, had steadily increasing relative incident heart failure rates of 29%, 97%, and 210%, respectively, compared with controls, reported Dr. Echouffo-Tcheugui, an endocrinologist at Johns Hopkins Medicine in Baltimore.

Similar rates of HFrEF and HFpEF

Among all 1,841 people in the dataset with diabetes for any length of time each additional 5 years of the disorder linked with a significant, relative 17% increase in the rate of incident heart failure. Incidence of heart failure rose even more sharply with added duration among those with a hemoglobin A1c of 7% or greater, compared with those with better glycemic control. And the rate of incident heart failure with reduced ejection fraction (HFrEF) roughly matched the rate of incident heart failure with preserved ejection fraction (HFpEF).

The study dataset included 9,734 adults enrolled into the Atherosclerosis Risk in Communities (ARIC) study, and during a median follow-up of 22.5 years they had nearly 2,000 episodes of either hospitalization or death secondary to incident heart failure. This included 617 (31%) events involving HFpEF, 495 events (25%) involving HFrEF, and 876 unclassified heart failure events.

The cohort averaged 63 years of age; 58% were women, 23% were Black, and 77% were White (the study design excluded people with other racial and ethnic backgrounds). The study design also excluded people with a history of heart failure or coronary artery disease, as well as those diagnosed with diabetes prior to age 18 resulting in a study group that presumably mostly had type 2 diabetes when diabetes was present. The report provided no data on the specific numbers of patients with type 1 or type 2 diabetes.

“It’s not surprising that a longer duration of diabetes is associated with heart failure, but the etiology remains problematic,” commented Robert H. Eckel, MD, an endocrinologist at the University of Colorado at Denver, Aurora. “The impact of diabetes on incident heart failure is not well know, particularly duration of diabetes,” although disorders often found in patients with diabetes, such as hypertension and diabetic cardiomyopathy, likely have roles in causing heart failure, he said.
 

Diabetes duration may signal need for an SGLT2 inhibitor

“With emerging novel treatments like the SGLT2 [sodium-glucose cotransporter 2] inhibitors for preventing heart failure hospitalizations and deaths in patients with type 2 diabetes, this is a timely analysis,” Dr. Eckel said in an interview.

“There is no question that with increased duration of type 2 diabetes” the need for an agent from the SGLT2-inhibitor class increases. Although, because of the proven protection these drugs give against heart failure events and progression of chronic kidney disease, treatment with this drug class should start early in patients with type 2 diabetes, he added.

Dr. Echouffo-Tcheugui and his coauthors agreed, citing two important clinical take-aways from their findings:

First, interventions that delay the onset of diabetes may potentially reduce incident heart failure; second, patients with diabetes might benefit from cardioprotective treatments such as SGLT2 inhibitors, the report said.

“Our observations suggest the potential prognostic relevance of diabetes duration in assessing heart failure,” the authors wrote. Integrating diabetes duration into heart failure risk estimation in people with diabetes “could help refine the selection of high-risk individuals who may derive the greatest absolute benefit from aggressive cardioprotective therapies such as SGLT2 inhibitors.”

The analysis also identified several other demographic and clinical factors that influenced the relative effect of diabetes duration. Longer duration was linked with higher rates of incident heart failure in women compared with men, in Blacks compared with Whites, in people younger than 65 compared with older people, in people with an A1c of 7% or higher, and in those with a body mass index of 30 kg/m² or greater.

The ARIC study and the analyses run by Dr. Echouffo-Tcheugui and his coauthors received no commercial funding. Dr. Echouffo-Tcheugui and Dr. Eckel had no relevant disclosures.

mzoler@mdedge.com