Orlando, FL—Heart failure with preserved ejection factor (HFpEF) is the most common phenotype of heart failure (HF) in the world and has become increasingly prominent as obesity rates rise.

That is according to Mikhail N. Kosiborod, MD, of the University of Missouri-Kansas City. Dr. Kosiborod participated in a discussion at the recent American Diabetes Association 84th Scientific Sessions in Orlando, Florida, on two trials of the of glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide. The drug led to similar improvement in symptoms and weight loss in patients with a BMI >30 who have HFpEF whether or not they also had diabetes. The symposium presenters urged greater use of the drug in HF patients.

According to the initial results of STEP-HFpEF (HFpEF patients without diabetes) and STEP-HFpEF-DM (HFpEF patients with diabetes), the combined Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) showed improvement of 7.5 points and body weight reduction of 8.4% versus placebo over 52 weeks.

In STEP-HFpEF-DM, the effects of semaglutide in 616 patients were evaluated in three categories of baseline A1C: <6.5%, 6.5% to < 7.5%, and ≥7.5%. For that study, 57% of patients aged between 65 and 75 years had a median A1C at baseline of 6.8% and a mean BMI of approximately 38. Most of the patients were male, and 84.3% were white.

“There was no impact of baseline A1C on KCCQ benefits,” explained Melanie J. Davies, CBE, MB, ChB, MD, of the University of Leicester, Leicester, United Kingdom. “And the same observation applies to body weight advantages.”

Baseline A1C also showed no influence on improvements in 6-minute walk distance, C-reactive protein high-sensitivity, or N-terminal prohormone of brain natriuretic peptide (NTproBNP), according to the report.

Dr. Davies noted that the overall reduction in A1C with semaglutide was 0.8%, with increasing reductions as baseline A1C increased.

While there were numerically fewer hypoglycemic events in the semaglutide arm, those patients were less likely to initiate any diabetes medication and more likely to discontinue any diabetes medication.

“Semaglutide significantly reduced A1C, but its HF benefits are likely driven by mechanisms beyond glycemia, including both weight loss-related and weight loss-independent effects,” Dr. Davies said.

What puzzled the researchers is the mechanisms by which semaglutide benefits HF. They noted that while semaglutide has similar HFpEF benefits regardless of diabetes, the mean weight loss in STEP-HFpEF was 10.7% compared with 6.4% in STEP-HFpEF-DM—nearly 40% lower.

“There is something more than weight loss at work,” suggested Javed Butler, MD, MPH, MBA, president, Baylor Scott and White Research Institute, and professor at the University of Mississippi.

In other differences:

• Patients with higher baseline NTproBNP benefited more than those with lower levels
• Those with New York Heart Association (NYHA) Functional Classification III or IV HF showed greater benefit than those with NYHA Class II
• Patients with atrial fibrillation had greater benefits than those without
• Patients on loop diuretics showed greater benefit than those not on the agents.

Semaglutide lowered NTproBNP versus placebo regardless of weight lost during the trial, and although the numbers were small, semaglutide was linked to a longer time to first HF event and time to first HF event or cardiovascular death.

“STEP-HF marks the beginning of a new era in the management of the obesity phenotype of HFpEF—arguably the most prevalent form of HFpEF globally—by changing the conversation about the role of obesity in the development and progression of HFpEF from a comorbidity to a root cause and treatment target,” said Subodh Verma, MD, PhD, of the University of Toronto.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.


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