Background:Patients with heart failure with reduced ejection fraction (HFrEF) and insulin-treated diabetes have a high risk of cardiovascular complications. Mineralocorticoid receptor antagonists may mitigate this risk. We aim to explore the effect of eplerenone on cardiovascular outcomes and all-cause mortality in HFrEF patients with diabetes, including those treated with insulin in the EMPHASIS-HF trial (Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms).Methods:The primary outcome was the composite of heart failure hospitalization or cardiovascular death. Cox models with treatment-by-diabetes subgroup interaction terms were used.Results:The median follow-up was 21 (10–33) months. Of the 2737 patients included, 623 (23%) had non-insulin-treated diabetes, 236 (9%) had insulin-treated diabetes and 1878 did not have diabetes. Patients with insulin-treated diabetes were younger, more often women, with higher body mass index, waist circumference, more frequent ischemic heart failure cause, impaired kidney function, and longer diabetes duration. Compared with patients without diabetes, those with insulin-treated diabetes had a 2-fold higher risk of having a primary outcome event. The hazard ratio (95% CI) for the effect of eplerenone, compared with placebo, on the primary outcome was 0.31 (0.19–0.50) in insulin-treated diabetes, 0.69 (0.50–0.93) in non-insulin-treated diabetes, and 0.72 (0.58–0.88) in patients without diabetes; interaction P=0.007. The annualized number needed-to-treat-to-benefit with regards to the primary outcome was 3 (95% CI, 3–4) in patients with insulin-treated diabetes, 16 (13–19) in patients with diabetes not receiving insulin, and 26 (24–28) in patients without diabetes.Conclusions:Patients with insulin-treated diabetes experienced a greater benefit from eplerenone than those with diabetes not treated with insulin and people without diabetes.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT00232180.

中文翻译：

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胰岛素治疗对依普利酮效果的影响：来自 EMPHASIS-HF 试验的见解

背景：射血分数降低的心力衰竭 (HFrEF) 和胰岛素治疗的糖尿病患者发生心血管并发症的风险很高。盐皮质激素受体拮抗剂可以减轻这种风险。我们旨在探索依普利酮对 HFrEF 糖尿病患者的心血管结局和全因死亡率的影响，包括在 EMPHASIS-HF 试验中接受胰岛素治疗的患者（依普利酮治疗收缩性心力衰竭和轻度症状患者）。方法：主要结果是心力衰竭住院或心血管死亡的复合。使用具有治疗-糖尿病亚组相互作用项的 Cox 模型。结果：中位随访时间为 21 (10-33) 个月。在包括的 2737 名患者中，623 名 (23%) 患有未接受胰岛素治疗的糖尿病，236 名 (9%) 患有接受胰岛素治疗的糖尿病，1878 名未患有糖尿病。接受胰岛素治疗的糖尿病患者更年轻，女性更多，体重指数、腰围更高，缺血性心力衰竭更常见，肾功能受损，糖尿病病程更长。与未患糖尿病的患者相比，接受胰岛素治疗的糖尿病患者发生主要结局事件的风险高 2 倍。与安慰剂相比，依普利酮对主要结局的影响的风险比 (95% CI) 在胰岛素治疗的糖尿病中为 0.31 (0.19–0.50)，在非胰岛素治疗的糖尿病中为 0.69 (0.50–0.93)，以及无糖尿病患者为 0.72 (0.58–0.88)；相互作用 与未患糖尿病的患者相比，接受胰岛素治疗的糖尿病患者发生主要结局事件的风险高 2 倍。与安慰剂相比，依普利酮对主要结局的影响的风险比 (95% CI) 在胰岛素治疗的糖尿病中为 0.31 (0.19–0.50)，在非胰岛素治疗的糖尿病中为 0.69 (0.50–0.93)，以及无糖尿病患者为 0.72 (0.58–0.88)；相互作用 与未患糖尿病的患者相比，接受胰岛素治疗的糖尿病患者发生主要结局事件的风险高 2 倍。与安慰剂相比，依普利酮对主要结局的影响的风险比 (95% CI) 在胰岛素治疗的糖尿病中为 0.31 (0.19–0.50)，在非胰岛素治疗的糖尿病中为 0.69 (0.50–0.93)，以及无糖尿病患者为 0.72 (0.58–0.88)；相互作用P = 0.007。在接受胰岛素治疗的糖尿病患者中，与主要结局相关的需要治疗才能获益的年化人数为 3（95% CI，3-4），未接受胰岛素治疗的糖尿病患者为 16（13-19） , 和 26 (24–28) 在非糖尿病患者中。结论：与未接受胰岛素治疗的糖尿病患者和非糖尿病患者相比，接受胰岛素治疗的糖尿病患者从依普利酮获得的益处更大。注册：URL：https://www.临床试验.gov；唯一标识符：NCT00232180。