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Recent research presented at the ESC Congress 2023 reveals that semaglutide offers notable benefits for patients experiencing heart failure along with obesity. This study demonstrates that semaglutide not only enhances symptoms linked to heart failure but also improves physical functioning. Moreover, it leads to more significant weight loss when compared to a placebo, particularly in individuals with heart failure with preserved ejection fraction (HFpEF) and obesity.
In the community, around half of heart failure patients suffer from HFpEF, a condition where the heart’s ejection fraction is preserved. The majority of these patients are overweight or obese. Current evidence suggests that obesity and excess adiposity are not mere comorbidities but may substantially contribute to the development and progression of HFpEF. Those with obesity-related HFpEF often experience pronounced symptoms like breathlessness, limited tolerance for physical activity, and swelling, all of which collectively diminish their quality of life. Unfortunately, available treatment options are limited, and there are no approved therapies that specifically target the obesity-related aspect of HFpEF.
Semaglutide, a potent agonist of the glucagon-like-peptide-1 receptor, has previously demonstrated substantial weight loss benefits for individuals with overweight and obesity. The STEP-HFpEF trial aimed to investigate whether semaglutide treatment could significantly enhance symptoms, physical limitations, exercise capacity, and weight loss in patients grappling with HFpEF and obesity.
The STEP-HFpEF trial was a meticulously conducted study involving randomization, double-blinding, and placebo control. Conducted across 96 sites in 13 different countries, the trial enrolled patients with HFpEF, a body mass index (BMI) of 30 kg/m² or higher, heart failure symptoms, and functional constraints (defined by New York Heart Association functional class II–IV and a Kansas City Cardiomyopathy Questionnaire Clinical Summary Score [KCCQ-CSS] of less than 90 points).
Participants were divided into two groups: one receiving once-weekly subcutaneous semaglutide at 2.4 mg and the other receiving a placebo, over a span of 52 weeks. The trial assessed two primary endpoints: the change in KCCQ-CSS, a recognized metric for heart failure symptoms and physical constraints, and the change in body weight. The trial also evaluated secondary endpoints including the alteration in the 6-minute walk distance (a validated measure of exercise capacity), a combined endpoint involving death, heart failure events, and changes in KCCQ-CSS and 6MWD, as well as modifications in C-reactive protein (CRP) levels, a marker of inflammation.
The trial included 529 patients, with a median age of 69 years and 56.1 percent being female. At baseline, their median body weight was 105.1 kg and median BMI was 37.0 kg/m². Patients started with considerable heart failure-related symptoms, physical limitations, and reduced exercise tolerance. The trial successfully met both primary endpoints and all confirmatory secondary endpoints.
Semaglutide showed a mean KCCQ-CSS increase of 16.6 points from baseline to week 52, compared to 8.7 points with the placebo. The change in body weight was -13.3 percent with semaglutide versus -2.6 percent with the placebo. For secondary endpoints, semaglutide displayed a greater change in 6MWD (21.5 meters) compared to the placebo (1.2 meters). The hierarchical composite endpoint favored semaglutide. Moreover, semaglutide led to a considerable decrease in CRP levels compared to the placebo.
Additional exploratory endpoints also showed promise. Semaglutide produced a greater reduction in NTproBNP at 52 weeks compared to the placebo. Notably, the incidence of heart failure hospitalization or urgent visits was significantly lower in the semaglutide group. However, there were slightly more serious adverse events reported with the placebo group.
Dr. Mikhail Kosiborod, the principal investigator of the study, emphasized that semaglutide treatment exhibited substantial improvements in symptoms, physical limitations, and exercise capacity for patients with HFpEF and obesity. He also noted that this study sheds light on the pivotal role of obesity in HFpEF and suggests a shift in therapeutic approaches.
Overall, the results of the STEP-HFpEF trial highlight the potential of semaglutide as a valuable treatment strategy for patients dealing with obesity-related HFpEF, addressing a significant gap in current therapeutic options.
