Background
The obesity phenotype of HFpEF is a pathophysiologically distinct form of HFpEF that is characterized by more severe symptoms, poorer exercise capacity, more adverse hemodynamics, and greater risk of HF hospitalization compared with HFpEF patients without obesity [1-8]. Recently, the STEP-HFpEF (Semaglutide Treatment Effect in People with obesity and HFpEF) trial showed that semaglutide reduced symptoms, physical limitations, inflammation, and body weight and improved exercise function in patients with the obesity phenotype of HFpEF compared with placebo [9,10]. However, it is unclear whether these treatment effects vary by obesity class and whether they are related to the magnitude of body weight reduction.
Aim of the study
In a prespecified analysis of the STEP-HFpEF trial, the authors investigated the efficacy of semaglutide versus placebo in HFpEF patients across different obesity categories and whether the degree of body weight reduction achieved with semaglutide was related to the improvements in the key trial endpoints.
Methods
The STEP-HFpEF trial was an international, double-blind, placebo-controlled RCT in which 529 patients with the obesity phenotype of HFpEF (LVEF â¥45%; NYHA class IIâIV HF symptoms; BMI â¥30 kg/m²) without diabetes were randomized to subcutaneous semaglutide 2.4âmg once weekly or placebo for 52 weeks, in addition to standard of care [10].
Outcomes
The dual primary endpoints of the STEP-HFpEF trial were change in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) and percent change in body weight from baseline to 52 weeks. Confirmatory secondary endpoints included change in 6-minute walk distance (6MWD), overall clinical benefit assessed using a hierarchical composite outcome (all-cause death, HF events, and several thresholds of change in KCCQ-CSS from baseline to 52 weeks and change in 6MWD â¥30âm), and change in CRP level from baseline to 52âweeks.
Safety and tolerability were assessed by reported serious adverse events and adverse events leading to premature treatment discontinuation.
Treatment effects by baseline obesity category
Association between semaglutide effects and weight change
Adverse events
In this prespecified analysis of the STEP-HFpEF trial among patients with the obesity phenotype of HFpEF, 52-week treatment with semaglutide versus placebo reduced body weight, HF-related symptoms, physical limitations, and systemic inflammation and improved exercise function, across all 3 obesity categories . In semaglutide-treated patients, the magnitude of benefit was associated with the degree of weight loss. According to the authors, âthese data support semaglutide-mediated weight loss as a key treatment strategy in patients with the obesity phenotype of HFpEFâ and âindicate that [those with only mild obesity] benefit just as much as patients with more severe obesity.â
Show references
1. Morgen, C. S. et al. Obesity, cardiorenal comorbidities and risk of hospitalization in patients with heart failure with preserved ejection fraction. Mayo Clin. Proc. https://doi.org/10.1016/j.mayocp.2023.07.008 (2023).
2. Dalos, D. et al. Functional status, pulmonary artery pressure, and clinical outcomes in heart failure with preserved ejection fraction. J. Am. Coll. Cardiol. 68, 189â199 (2016).
3. Kitzman, D. W. & Shah, S. J. The HFpEF obesity phenotype: the elephant in the room. J. Am. Coll. Cardiol. 68, 200â203 (2016).
4. Obokata, M., Reddy, Y. N. V., Pislaru, S. V., Melenovsky, V. & Borlaug, B. A. Evidence supporting the existence of a distinct obese phenotype of heart failure with preserved ejection fraction. Circulation 136, 6â19 (2017).
5. Reddy, Y. N. V. et al. Characterization of the obese phenotype of heart failure with preserved ejection fraction: a RELAX trial ancillary study. Mayo Clin. Proc. 94, 1199â1209 (2019).
6. Reddy, Y. N. V. et al. Quality of life in heart failure with preserved ejection fraction: importance of obesity, functional capacity, and physical inactivity. Eur. J. Heart Fail. 22, 1009â1018 (2020).
7. Adamson, C. et al. Dapagliflozin for heart failure according to body mass index: the DELIVER trial. Eur. Heart J. 43, 4406â4417 (2022).
8. Borlaug, B. A. et al. Obesity and heart failure with preserved ejection fraction: new insights and pathophysiological targets. Cardiovasc. Res. 118, 3434â3450 (2023).
9. Kosiborod, M. N. et al. Once weekly semaglutide in heart failure with preserved ejection fraction and obesity. N. Engl. J. Med. (in the press).
10. Kosiborod, M. N. et al. Design and baseline characteristics of STEP-HFpEF program evaluating semaglutide in patients with obesity HFpEF phenotype. JACC Heart Fail. 11, 1000â1010 (2023).
Facebook Comments