A New Game Changer for HFpEF

Heart failure with a preserved ejection fraction (HFpEF) has remained an elusive disease with respect to effective therapeutic target. Many of the standard drugs for heart failure like ACE inhibitors and beta-blockers have proven marginally effective when treating HFpEF. It was only recently that the SGLT2 inhibitors finally broke through with some positive data, which resulted in these agents receiving the first class I indication for HFpEF in the most recent HF guidelines.

GLP-1 agonists like semaglutide have proven very effective for reducing rates of major adverse cardiac events in patients with diabetes. They have also recently proven very effective for weight loss, so much so that it’s becoming difficult for patients to find a supply of these drugs given how popular they’ve become.

In this week’s issue of Talking Therapeutics, we explore a new study that evaluated the effect of semaglutide in patients categorized as obese with HFpEF.

Point 1: Preliminary Data Looks Good

This new paper randomized over 500 patients categorized as obese (BMI greater than 30) with HFpEF to semaglutide 2.4 mg weekly or placebo. The dual primary end points were the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) and the change in body weight.

The mean change in the KCCQ-CSS was 16.6 points with semaglutide and 8.7 points with placebo (estimated difference, 7.8 points; 95% confidence interval [CI], 4.8 to 10.9; P<0.001), indicating a greater improvement in heart failure related quality of life with semaglutide. The mean percentage change in body weight was −13.3% with semaglutide and −2.6% with placebo (estimated difference, −10.7 percentage points; 95% CI, −11.9 to −9.4; P<0.001). The authors also looked at several secondary endpoints, and the mean change in the 6-minute walk distance was 21.5 m with semaglutide and 1.2 m with placebo (estimated difference, 20.3 m; 95% CI, 8.6 to 32.1; P<0.001). This indicates an improvement in overall functional status with semaglutide therapy.

The authors also found that the mean percentage change in the CRP level was –43.5% with semaglutide and –7.3% with placebo (estimated treatment ratio, 0.61; 95% CI, 0.51 to 0.72; P<0.001), which indicates a reduction in a dangerous biomarker that indicates ongoing inflammation. Finally, serious adverse events were reported in 35 participants (13.3%) in the semaglutide group and 71 (26.7%) in the placebo group.

Point 2: This Is Only the First Step

Overall, this trial found that obese patients with HFpEF who took semaglutide lost weight, felt better, and had improvements in functional status and decreases in residual inflammatory markers. These are all important endpoints, and the results of this trial will likely lead to the development of a larger trial aimed at assessing rates of mortality and hospitalization due to heart failure.