BACKGROUND Obesity increases the risk of heart failure with preserved ejection fraction. Tirzepatide, a long-acting agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, causes considerable weight loss, but data are lacking with respect to its effects on cardiovascular outcomes. METHODS In this international, double-blind, randomized, placebo-controlled trial, we randomly assigned, in a 1:1 ratio, 731 patients with heart failure, an ejection fraction of at least 50%, and a body-mass index (the weight in kilograms divided by the square of the height in meters) of at least 30 to receive tirzepatide (up to 15 mg subcutaneously once per week) or placebo for at least 52 weeks. The two primary end points were a composite of adjudicated death from cardiovascular causes or a worsening heart-failure event (assessed in a time-to-first-event analysis) and the change from baseline to 52 weeks in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating better quality of life). RESULTS A total of 364 patients were assigned to the tirzepatide group and 367 to the placebo group; the median duration of follow-up was 104 weeks. Adjudicated death from cardiovascular causes or a worsening heart-failure event occurred in 36 patients (9.9%) in the tirzepatide group and in 56 patients (15.3%) in the placebo group (hazard ratio, 0.62; 95% confidence interval [CI], 0.41 to 0.95; P = 0.026). Worsening heart-failure events occurred in 29 patients (8.0%) in the tirzepatide group and in 52 patients (14.2%) in the placebo group (hazard ratio, 0.54; 95% CI, 0.34 to 0.85), and adjudicated death from cardiovascular causes occurred in 8 patients (2.2%) and 5 patients (1.4%), respectively (hazard ratio, 1.58; 95% CI, 0.52 to 4.83). At 52 weeks, the mean (±SD) change in the KCCQ-CSS was 19.5±1.2 in the tirzepatide group as compared with 12.7±1.3 in the placebo group (between-group difference, 6.9; 95% CI, 3.3 to 10.6; P<0.001). Adverse events (mainly gastrointestinal) leading to discontinuation of the trial drug occurred in 23 patients (6.3%) in the tirzepatide group and in 5 patients (1.4%) in the placebo group. CONCLUSIONS Treatment with tirzepatide led to a lower risk of a composite of death from cardiovascular causes or worsening heart failure than placebo and improved health status in patients with heart failure with preserved ejection fraction and obesity. (Funded by Eli Lilly; SUMMIT ClinicalTrials.gov number, NCT04847557.).

中文翻译：

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Tirzepatide 治疗射血分数保留和肥胖的心力衰竭。


背景 肥胖会增加射血分数保留的心力衰竭风险。Tirzepatide 是葡萄糖依赖性促胰岛素多肽和胰高血糖素样肽-1 受体的长效激动剂，可显着减轻体重，但缺乏关于其对心血管结局影响的数据。方法 在这项国际、双盲、随机、安慰剂对照试验中，我们以 1：1 的比例随机分配了 731 名心力衰竭患者，射血分数至少为 50%，体重指数（以公斤为单位的体重除以以米为单位的身高的平方）接受 tirzepatide（最多 15 毫克，皮下注射，每周一次）或安慰剂至少 52 周。两个主要终点是被判定为心血管原因死亡或心力衰竭事件恶化（在首次事件发生时间分析中评估）和堪萨斯城心肌病问卷临床总分 （KCCQ-CSS;分数范围从 0 到 100，分数越高表示生活质量越好） 中从基线到 52 周的变化。结果 共 364 例患者被分配到 tirzepatide 组，367 例被分配到安慰剂组;中位随访时间为 104 周。tirzepatide 组有 36 名患者 （9.9%） 和安慰剂组有 56 名患者 （15.3%） 被判定死于心血管原因或心力衰竭事件恶化（风险比，0.62;95% 置信区间 [CI]，0.41 至 0.95;P = 0.026）。tirzepatide 组有 29 例患者 （8.0%） 发生心力衰竭事件恶化，安慰剂组有 52 例患者 （14.2%） 发生 （风险比，0.54;95% CI，0.34 至 0.85），判定心血管原因死亡发生在 8 例患者 （2.2%） 和 5 例患者 （1.4%），分别（风险比，1.58;95% CI，0.52 至 4.83）。52 周时，tirzepatide 组 KCCQ-CSS 的平均 （±SD） 变化为 19.5±1.2，而安慰剂组为 12.7±1.3（组间差异，6.9;95% CI，3.3 至 10.6;P<0.001）。导致试验药物停药的不良事件（主要是胃肠道）发生在 tirzepatide 组的 23 名患者 （6.3%） 和安慰剂组的 5 名患者 （1.4%） 中。结论与安慰剂相比，tirzepatide 治疗导致心血管原因导致复合死亡或心力衰竭恶化的风险降低，并改善射血分数保留和肥胖的心力衰竭患者的健康状况。（由 Eli Lilly 资助;SUMMIT ClinicalTrials.gov 编号，NCT04847557.）。