Background:Empagliflozin improves outcomes in patients with heart failure with a preserved ejection fraction, but whether the effects are consistent in patients with and without diabetes remains to be elucidated.Methods:Patients with class II through IV heart failure and a left ventricular ejection fraction >40% were randomized to receive empagliflozin 10 mg or placebo in addition to usual therapy. We undertook a prespecified analysis comparing the effects of empagliflozin versus placebo in patients with and without diabetes.Results:Of the 5988 patients enrolled, 2938 (49%) had diabetes. The risk of the primary outcome (first hospitalization for heart failure or cardiovascular death), total hospitalizations for heart failure, and estimated glomerular filtration rate decline was higher in patients with diabetes. Empagliflozin reduced the rate of the primary outcome irrespective of diabetes status (hazard ratio, 0.79 [95% CI, 0.67, 0.94] for patients with diabetes versus hazard ratio, 0.78 [95% CI, 0.64, 0.95] in patients without diabetes; P_interaction=0.92). The effect of empagliflozin to reduce total hospitalizations for heart failure was also consistent in patients with and without diabetes. The effect of empagliflozin to attenuate estimated glomerular filtration rate decline during double-blind treatment was also present in patients with and without diabetes, although more pronounced in patients with diabetes (1.77 in diabetes versus 0.98 mL/min/1.73m² in patients without diabetes; P_interaction=0.01). Across these 3 end points, the effect of empagliflozin did not differ in patients with prediabetes or normoglycemia (33% and 18% of the patient population, respectively). When investigated as a continuous variable, baseline hemoglobin A1c did not modify the effects on the primary outcome (P_interaction=0.26). There was no increased risk of hypoglycemic events in either subgroup as compared with placebo.Conclusions:In patients with heart failure and a preserved ejection fraction enrolled in the EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction), empagliflozin significantly reduced the risk of heart failure outcomes irrespective of diabetes status at baseline.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03057951.

中文翻译：

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Empagliflozin 治疗左心室射血分数保留的心力衰竭伴或不伴糖尿病

背景：恩格列净可改善射血分数保留的心力衰竭患者的预后，但这种效果在糖尿病患者和非糖尿病患者中是否一致仍有待阐明。方法：II 至 IV 级心力衰竭患者和左心室射血分数 >除了常规治疗外，40% 的患者被随机分配接受 empagliflozin 10 mg 或安慰剂。我们进行了一项预先指定的分析，比较了恩格列净与安慰剂对糖尿病患者和非糖尿病患者的影响。结果：在 5988 名入选患者中，2938 名 (49%) 患有糖尿病。糖尿病患者的主要结局（因心力衰竭或心血管死亡首次住院）、因心力衰竭住院总次数和估计肾小球滤过率下降的风险较高。P_相互作用=0.92）。empagliflozin 减少心力衰竭总住院率的效果在糖尿病患者和非糖尿病患者中也一致。在双盲治疗期间，empagliflozin 减轻估计肾小球滤过率下降的作用也存在于糖尿病患者和非糖尿病患者中，尽管在糖尿病患者中更为明显（糖尿病患者为 1.77 vs非糖尿病患者为 0.98 mL/min/1.73m ² ; P_相互作用=0.01)。在这 3 个终点中，empagliflozin 的效果在糖尿病前期或血糖正常的患者中没有差异（分别占患者人群的 33% 和 18%）。当作为连续变量进行研究时，基线血红蛋白 A1c 不会改变对主要结果的影响（P_相互作用=0.26)。与安慰剂组相比，两个亚组的低血糖事件风险均未增加。结论：在 EMPEROR-Preserved（射血分数保留的慢性心力衰竭患者的恩格列净结果试验）中登记的射血分数保留的心力衰竭患者中， empagliflozin 显着降低了心力衰竭结果的风险，无论基线时的糖尿病状态如何。注册：URL：https://www.clinicaltrials.gov；唯一标识符：NCT03057951。