Background:Empagliflozin reduces the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure with preserved ejection fraction, but additional data are needed about its effect on inpatient and outpatient heart failure events.Methods:We randomly assigned 5988 patients with class II through IV heart failure with an ejection fraction of >40% to double-blind treatment with placebo or empagliflozin (10 mg once daily), in addition to usual therapy, for a median of 26 months. We prospectively collected information on inpatient and outpatient events reflecting worsening heart failure and prespecified their analysis in individual and composite end points.Results:Empagliflozin reduced the combined risk of cardiovascular death, hospitalization for heart failure, or an emergency or urgent heart failure visit requiring intravenous treatment (432 versus 546 patients [empagliflozin versus placebo, respectively]; hazard ratio, 0.77 [95% CI, 0.67–0.87]; P<0.0001). This benefit reached statistical significance at 18 days after randomization. Empagliflozin reduced the total number of heart failure hospitalizations that required intensive care (hazard ratio, 0.71 [95% CI, 0.52–0.96]; P=0.028) and the total number of all hospitalizations that required a vasopressor or positive inotropic drug (hazard ratio, 0.73 [95% CI, 0.55–0.97]; P=0.033). Compared with patients in the placebo group, fewer patients in the empagliflozin group reported outpatient intensification of diuretics (482 versus 610; hazard ratio, 0.76 [95% CI, 0.67–0.86]; P<0.0001), and patients assigned to empagliflozin were 20% to 50% more likely to have a better New York Heart Association functional class, with significant effects at 12 weeks that were maintained for at least 2 years. The benefit on total heart failure hospitalizations was similar in patients with an ejection fraction of >40% to <50% and 50% to <60%, but was attenuated at higher ejection fractions.Conclusions:In patients with heart failure with preserved ejection fraction, empagliflozin produced a meaningful, early, and sustained reduction in the risk and severity of a broad range of inpatient and outpatient worsening heart failure events.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03057977.

中文翻译：

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恩格列净对射血分数保留的心力衰竭患者心力衰竭事件恶化的影响：EMPEROR-Preserved 试验

背景：恩格列净可降低射血分数保留的心力衰竭患者的心血管死亡或因心力衰竭住院的风险，但需要更多数据来了解其对住院和门诊心力衰竭事件的影响。方法：我们随机分配了 5988 名 II 类患者射血分数 >40% 的 IV 性心力衰竭患者在常规治疗基础上接受安慰剂或恩格列净（10 mg 每日一次）双盲治疗，中位治疗时间为 26 个月。我们前瞻性地收集了反映心力衰竭恶化的住院和门诊事件的信息，并预先设定了对个体和复合终点的分析。结果：恩格列净降低了心血管死亡、心力衰竭住院或需要静脉注射的紧急或紧急心力衰竭就诊的综合风险治疗（432 名患者与 546 名患者[分别为恩格列净与安慰剂]；风险比，0.77 [95% CI，0.67-0.87]；P <0.0001）。这一益处在随机分组后 18 天达到统计学显着性。恩格列净减少了需要重症监护的心力衰竭住院总数（风险比，0.71 [95% CI，0.52-0.96]；P = 0.028）和需要血管加压药或正性肌力药物的所有住院总数（风险比） ，0.73 [95% CI，0.55–0.97]；P = 0.033）。与安慰剂组患者相比，恩格列净组报告门诊强化利尿剂的患者较少（482 例与 610 例；风险比，0.76 [95% CI，0.67–0.86]；P <0.0001），分配至恩格列净组的患者为 20 例获得更好的纽约心脏协会功能分级的可能性增加 % 至 50%，12 周时效果显着，且至少能维持 2 年。射血分数 >40% 至 <50% 和 50% 至 <60% 的患者在完全心力衰竭住院方面的获益相似，但射血分数较高时会减弱。结论：在射血分数保留的心力衰竭患者中，恩格列净对多种住院和门诊恶化心力衰竭事件的风险和严重程度产生了有意义的、早期和持续的降低。唯一标识符：NCT03057977。