In the Semaglutide Treatment Effect in People with obesity and HFpEF (STEP-HFpEF) program, semaglutide improved heart failure (HF)-related symptoms, physical limitations, and exercise function, and reduced bodyweight in patients with obesity-related heart failure with preserved ejection fraction (HFpEF). Whether semaglutide improves functional status, as assessed by NYHA functional class, is unknown. The goal of this study was to examine the effects of semaglutide on change in NYHA functional class over time. We also investigated the effects of semaglutide on HF-related symptoms, physical limitations, and bodyweight and other trial endpoints across baseline NYHA functional class categories. This was a prespecified analysis of pooled data from 2 international, double-blind, randomized trials (STEP-HFpEF and STEP-HFpEF type 2 diabetes [STEP-HFpEF DM], comprising the STEP-HFpEF program), which collectively randomized 1,145 participants with obesity-related HFpEF to once-weekly semaglutide 2.4 mg or placebo for 52 weeks. The outcome of interest for this analysis was the change in NYHA functional class (baseline to 52 weeks). We also investigated the effects of semaglutide on the dual primary, confirmatory secondary, and selected exploratory endpoints according to baseline NYHA functional class. More semaglutide-treated than placebo-treated patients had an improvement in NYHA functional class (32.6% vs 21.5%, respectively; OR: 2.20 [95% CI: 1.62-2.99; < 0.001]) and fewer semaglutide-treated patients experienced deterioration in NYHA functional class (2.09% vs 5.24%, respectively; OR: 0.36 [95% CI: 0.19-0.70; = 0.003]) at 52 weeks. Semaglutide (vs placebo) improved the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CCS) across NYHA functional class categories; this was especially pronounced in those in NYHA functional classes III/IV (10.5 points [95% CI: 6.6-14.4 points]) vs NYHA functional class II (6.0 points [95% CI: 3.4-8.6 points]) ( interaction = 0.06). By contrast, the degree of reduction in bodyweight was similar with semaglutide vs placebo regardless of baseline NYHA functional class category (NYHA functional class II, −8.4% [95% CI: −9.4% to −7.3%]; NYHA functional classes III/IV, −8.3% [95% CI: −9.9% to −6.8%]; interaction = 0.96). Semaglutide consistently improved 6-minute walking distance (6MWD), the hierarchical composite endpoint (death, HF events, differences in KCCQ-CSS, and 6MWD changes), and reduced C-reactive protein and N-terminal prohormone of brain natriuretic peptide across NYHA functional class categories (all interactions = NS). In patients with obesity-related HFpEF, fewer semaglutide-treated than placebo-treated patients had a deterioration, and more had an improvement, in NYHA functional class at 52 weeks. Semaglutide consistently improved HF-related symptoms, physical limitations, and exercise function, and reduced bodyweight and biomarkers of inflammation and congestion in all NYHA functional class categories. Semaglutide-mediated improvements in health status were especially large in patients with NYHA functional classes III/IV. (Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure and Obesity; ) (Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes; )

中文翻译：

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索马鲁肽和 NYHA 功能分级治疗射血分数保留的肥胖相关性心力衰竭：STEP-HFpEF 计划


在索马鲁肽对肥胖和 HFpEF 患者的治疗效果 (STEP-HFpEF) 项目中，索马鲁肽改善了心力衰竭 (HF) 相关症状、身体限制和运动功能，并降低了肥胖相关心力衰竭患者的体重，并保留了射血功能分数（HFpEF）。根据 NYHA 功能分级评估，索马鲁肽是否可以改善功能状态尚不清楚。本研究的目的是检查索马鲁肽对 NYHA 功能等级随时间变化的影响。我们还研究了索马鲁肽对心力衰竭相关症状、身体限制、体重和其他 NYHA 功能类别基线试验终点的影响。这是对来自 2 项国际双盲随机试验（STEP-HFpEF 和 STEP-HFpEF 2 型糖尿病 [STEP-HFpEF DM]，组成 STEP-HFpEF 项目）的汇总数据进行的预先指定分析，该试验将 1,145 名参与者随机分组为肥胖相关的 HFpEF 改为每周一次 2.4 mg 索马鲁肽或安慰剂，持续 52 周。该分析感兴趣的结果是 NYHA 功能分级（基线至 52 周）的变化。我们还根据基线 NYHA 功能分级研究了索马鲁肽对双重主要终点、验证性次要终点和选定的探索性终点的影响。与安慰剂治疗相比，更多接受索马鲁肽治疗的患者的 NYHA 功能分级有所改善（分别为 32.6% vs 21.5%；OR：2.20 [95% CI：1.62-2.99；< 0.001]），接受索马鲁肽治疗的患者出现病情恶化的患者较少第 52 周时的 NYHA 功能分级（分别为 2.09% 与 5.24%；OR：0.36 [95% CI：0.19-0.70；= 0.003]）。 索马鲁肽（与安慰剂相比）改善了 NYHA 功能类别类别的堪萨斯城心肌病问卷临床总结评分 (KCCQ-CCS)；这在 NYHA 功能类别 III/IV 组（10.5 分 [95% CI：6.6-14.4 分]）与 NYHA 功能类别 II 组（6.0 分 [95% CI：3.4-8.6 分]）中尤其明显（交互作用 = 0.06 ）。相比之下，无论基线 NYHA 功能类别如何，索马鲁肽与安慰剂的体重减轻程度相似（NYHA 功能类别 II，-8.4% [95% CI：-9.4% 至 -7.3%]；NYHA 功能类别 III/ IV，-8.3% [95% CI：-9.9% 至 -6.8%]；交互作用 = 0.96）。索马鲁肽在 NYHA 中持续改善 6 分钟步行距离 (6MWD)、分层复合终点（死亡、心力衰竭事件、KCCQ-CSS 差异和 6MWD 变化），并降低 C 反应蛋白和脑钠尿肽 N 末端激素原功能类类别（所有交互= NS）。在患有肥胖相关 HFpEF 的患者中，第 52 周时，接受索马鲁肽治疗的患者的 NYHA 功能分级恶化的患者数量少于安慰剂治疗的患者，而更多的患者则有改善。索马鲁肽持续改善心力衰竭相关症状、身体限制和运动功能，并降低体重以及所有 NYHA 功能类别类别中炎症和充血的生物标志物。索马鲁肽介导的健康状况改善在 NYHA 功能分级 III/IV 级患者中尤其明显。（关于索马鲁肽对心力衰竭和肥胖患者的疗效的研究；）（关于索马鲁肽对心力衰竭、肥胖和 2 型糖尿病患者的疗效的研究；）