Rossello Xavier, Ferreira João Pedro, Pocock Stuart J, McMurray John J V, Solomon Scott D, Lam Carolyn S P, Girerd Nicolas, Pitt Bertram, Rossignol Patrick, Zannad Faiez
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
Department of Cardiology, Hospital Universitari Son Espases (HUSE), Mallorca, Spain.
Eur J Heart Fail. 2020 May;22(5):834-844. doi: 10.1002/ejhf.1740. Epub 2020 Feb 19.
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).
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.
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.
在个体随机临床试验（RCT）中，心力衰竭（HF）女性患者的代表性不足。关于HF药物的性别特异性治疗效果知之甚少。我们在主要的HF盐皮质激素受体拮抗剂（MRA）试验中评估了对MRA反应的性别差异，这些试验包括广泛的左心室射血分数（LVEF）范围。
使用在三项安慰剂对照RCT中招募的6167例患者（31.4%为女性）进行个体患者数据固定效应荟萃分析：随机螺内酯评估研究（RALES）、依普利酮用于轻度患者心力衰竭住院和生存研究（EMPHASIS-HF）以及螺内酯用于射血分数保留的心力衰竭（TOPCAT）-美洲研究。与男性相比，女性年龄更大，体重指数更高，肾小球滤过率更低。她们的LVEF也更高，纽约心脏协会功能分级更差，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更小。女性安慰剂组的事件发生率低于男性（每100人年15.4 vs. 22.1；P = 0.002）。MRA在男性和女性中均持续降低心血管死亡或HF住院的相对风险（交互作用P = 0.83）、心血管死亡（交互作用P = 0.44）和全因死亡（交互作用P = 0.19）。在对潜在混杂因素进行调整后，这些发现仍然一致，无论LVEF如何。在中位22个月的随访期间，MRA对高钾血症发生率和肾功能恶化没有性别特异性影响。
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有很大不同。尽管如此，这项荟萃分析支持MRA无论性别均有一致且有益的效果。
