AIMS Women with heart failure (HF) are under-represented in individual randomized clinical trials (RCTs). Little is known about sex-specific treatment effects in HF medications. We evaluated sex differences in the response to mineralocorticoid receptor antagonists (MRAs) in major HF MRA trials, including a broad spectrum of left ventricular ejection fraction (LVEF). METHODS AND RESULTS Individual patient data fixed-effect meta-analysis was performed using 6167 patients (31.4% were women) recruited in three placebo-controlled RCTs: Randomized Aldactone Evaluation Study (RALES), Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) and Spironolactone for Heart Failure with Preserved Ejection Fraction (TOPCAT)-Americas. Compared to men, women were older, had higher body mass index and lower glomerular filtration rate. They also had higher LVEF and poorer New York Heart Association functional class and were less likely to be taking angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers. Placebo-arm event rates were lower for women compared with men (15.4 vs. 22.1 per 100 person-year; P = 0.002). MRAs reduced consistently, in men and women, the relative risk for cardiovascular death or HF hospitalization (P for interaction = 0.83), cardiovascular death (P for interaction = 0.44) and all-cause death (P for interaction = 0.19). These findings remained consistent after adjustment for potential confounders, regardless of LVEF. There was no sex-specific impact of MRA on the rate of hyperkalaemia and worsening renal function during the median 22 months of follow-up. CONCLUSION In three large MRA RCTs, women were substantially different from men with regard to their clinical features and event rates. Nonetheless, this meta-analysis supports a consistent and beneficial MRA effect regardless of sex.

中文翻译：

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盐皮质激素受体拮抗剂试验中的性别差异：三项大型临床试验的汇总分析。

目的在个体随机临床试验（RCT）中，患有心力衰竭（HF）的女性人数不足。关于HF药物中针对性别的治疗效果知之甚少。在主要的HF MRA试验中，我们评估了对盐皮质激素受体拮抗剂（MRA）反应的性别差异，包括广泛的左心室射血分数（LVEF）。方法和结果对3项安慰剂对照RCT中招募的6167例患者（31.4％为女性）进行了个体患者数据固定效果荟萃分析：随机阿迪内通评估研究（RALES），轻度患者住院治疗中的依普利农和心衰生存研究。 （EMPHASIS-HF）和螺内酯治疗具有保留射血分数（TOPCAT）-美国的心力衰竭。与男性相比，女性年龄更大，具有较高的体重指数和较低的肾小球滤过率。他们的LVEF较高，纽约心脏协会的功能水平较差，服用血管紧张素转换酶抑制剂/血管紧张素II受体阻滞剂的可能性较小。女性的安慰剂组发生率比男性低（每100人年15.4比22.1； P = 0.002）。在男性和女性中，MRA持续降低心血管死亡或HF住院的相对风险（相互作用的P = 0.83），心血管死亡（相互作用的P = 0.44）和全因死亡（相互作用的P = 0.19）。不管是否使用LVEF，对潜在的混杂因素进行调整后，这些发现仍保持一致。在中位数的22个月随访期间，MRA对高钾血症和肾功能恶化没有性别特异性影响。结论在三项大型MRA RCT中，女性在临床特征和事件发生率方面与男性大不相同。尽管如此，这项荟萃分析支持一贯且有益的MRA效果，无论性别如何。