Vulnerable, but treatable: Semaglutide reduces symptoms in high-risk heart failure patients
Semaglutide has been associated with improved heart failure symptoms and considerable weight loss in patients with heart failure with preserved ejection fraction (HFpEF). It remains unclear, however, how this changes if the HFpEF patient is especially frail.
To learn more, a team of researchers explored data from more than 1,000 adults who previously participated in the STEP-HFpEF and STEP-HFpEF DM clinical trials. The group published its findings in JACC: Heart Failure.[1]
“Addressing these knowledge gaps is critically important because GLP-1 receptor agonist–induced weight loss has been associated with a substantial reduction in skeletal muscle and loss of bone mineral density in previous studies among individuals without heart failure,” wrote first author Ambarish Pandey MD, MSCS, a cardiologist with University of Texas Southwestern Medical Center, and colleagues. “This issue may be uniquely challenging in frail patients with HFpEF who have preexisting sarcopenia, skeletal muscle dysfunction, and increased physical function impairment. Additional loss of skeletal muscle and bone mass may result in further decline of physical function and a higher risk of adverse outcomes and disability.”
Pandey et al. evaluated each HFpEF patient’s frailty by looking at their medical history, vital signs and laboratory data. They also reviewed answers about quality of life from questionnaires each patient filled out at the start of the studies.
This was a substantially frail group. Out of 1,145 patients from STEP-HFpEF and STEP-HFpEF DM, 60.4% of patients were categorized as being the most frail, 30% were categorized as more frail and 9.6% were considered nonfrail.
These patients were all randomized to either undergo treatment with semaglutide or a placebo for 52 weeks. The authors then compared Kansas City Cardiomyopathy Questionnaire answers from before and after those 52 weeks.
Overall, treatment with semaglutide was consistently associated with weight loss and improved heart failure symptoms in these patients—and the benefits seemed to actually increase for patients who were the most frail.
“The findings of greater semaglutide treatment benefits among the most frail patients with obesity-related HFpEF are consistent with earlier reports of treatment effect modification by frailty status for other heart failure therapies,” the authors wrote. “These observations suggest that frailty-associated adverse functional and clinical outcomes in HFpEF are modifiable by using evidence-based therapies, including GLP-1 receptor agonists.”
The researchers did note that weight loss was comparable for all patients; being more frail did not appear to mean a patient is going to lose additional weight when undergoing treatment with semaglutide.
Reviewing their findings, the authors emphasized that using GLP-1 drugs such as semaglutide in frail HFpEF patients has been “a matter of debate” in the past due to a fear that there may be added risks.
“Our study findings alleviate these concerns and demonstrate greater HF-related benefits in most frail participants, alongside fewer serious adverse events with semaglutide (vs placebo) across the frailty strata,” the group concluded. “The greater treatment benefits of semaglutide among the most frail patients and its favorable effects on the frailty burden over time highlight its potential role as an effective treatment for these high-risk, vulnerable patients who have the most need for such therapies.”
Semaglutide is a GLP-1 receptor agonist sold by Novo Nordisk under the brand names Wegovy and Ozempic. It has been previously associated with a long list of health benefits, including several associated with improvements in cardiovascular symptoms in patients with and without diabetes.
This analysis was funded by Novo Nordisk.
Click here to read the full study in JACC: Heart Failure.
Michael has more than 19 years of experience as a professional writer and editor. He has written at length about cardiology, radiology, artificial intelligence and other key healthcare topics.