National Heart Centre Singapore, 5 Hospital Drive, Level 10, Singapore, 169609, Singapore.
Department of Cardiology, Clinical Sciences, Lund University, Skåne University Hospital, Lund, SE-221 85, Sweden.
ESC Heart Fail. 2022 Aug;9(4):2753-2761. doi: 10.1002/ehf2.13974. Epub 2022 May 23.
Recent studies have suggested potential sex differences in treatment response to pharmacological therapies in heart failure (HF). We performed a systematic review and meta-analysis of studies comparing treatment effects between men and women with HF and reduced ejection fraction (HFrEF) using established guideline-directed medical therapy and other emerging pharmacological treatments.
Systematic search was performed on PubMed, Embase, and Cochrane Library for randomized controlled trials published in 1990-2021. Outcomes were all-cause mortality and combined outcome of all-cause mortality and/or hospitalization for HF. Of 618 articles identified, 25 articles and 100 213 patients (mean age 62 ± 1.7 years, women 23.1%, mean left ventricular ejection fraction 26.6 ± 1.3%) were included in the systematic review and meta-analysis. For the outcome of all-cause mortality, there was no evidence of treatment heterogeneity by sex for renin-angiotensin system inhibitors (RASi) [hazard ratio (HR) 0.86 (95% confidence interval 0.75-0.99) in men; HR 0.97 (0.77-1.23) in women; P = 0.288], or for beta-blockers (BB) [HR 0.71 (0.59-0.86) in men; HR 0.87 (0.73-1.03) in women; P = 0.345]. Similarly, for the composite outcome of death or HF hospitalization, there was no evidence of treatment heterogeneity by sex for RASi [HR 0.84 (0.77-0.93) in men; HR 0.94 (0.81-1.08) in women; P = 0.210] or BB [HR 0.76 (0.64-0.90) in men; HR 0.72 (0.60-0.86) in women; P = 0.650]. Results for mineralocorticoid receptor antagonists (MRA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) from previously published meta-analyses were included in the review. For the combined outcome of cardiovascular death or HF hospitalization, no significant interaction for sex was observed for MRA (P = 0.78) or SGLT2i (P = 0.37). Results for emerging pharmacological treatments, such as soluble guanylate cyclase stimulators and cardiac myosin activators, were included in the review and showed consistent treatment effects between men and women.
Our meta-analysis showed no differences between sex in treatment effect for BB and RASi. Review on previously published trials for MRA, SGLT2i, and emerging therapies presented consistent treatment effects between men and women.
最近的研究表明，心力衰竭（HF）患者对药物治疗的反应存在潜在的性别差异。我们对使用既定指南指导的医学治疗和其他新兴药物治疗比较男性和女性心力衰竭射血分数降低（HFrEF）患者治疗效果的研究进行了系统评价和荟萃分析。
在 PubMed、Embase 和 Cochrane Library 上对 1990 年至 2021 年发表的随机对照试验进行了系统搜索。结局为全因死亡率和全因死亡率和/或 HF 住院的联合结局。在 618 篇文章中，有 25 篇文章和 100213 名患者（平均年龄 62±1.7 岁，女性 23.1%，平均左心室射血分数 26.6±1.3%）被纳入系统评价和荟萃分析。对于全因死亡率的结局，血管紧张素转换酶抑制剂（ACEI）或血管紧张素受体阻滞剂（ARB）[男性的危险比（HR）0.86（95%置信区间 0.75-0.99）；女性的 HR 0.97（0.77-1.23）；P=0.288]或β受体阻滞剂（BB）[男性的 HR 0.71（0.59-0.86）；女性的 HR 0.87（0.73-1.03）；P=0.345]的治疗效果没有性别差异。同样，对于死亡或 HF 住院的复合结局，血管紧张素受体脑啡肽酶抑制剂（ARNI）[男性的 HR 0.84（0.77-0.93）；女性的 HR 0.94（0.81-1.08）；P=0.210]或 BB[男性的 HR 0.76（0.64-0.90）；女性的 HR 0.72（0.60-0.86）；P=0.650]的治疗效果也没有性别差异。先前发表的荟萃分析中 MRAs 和 SGLT2i 的结果也包括在综述中。对于心血管死亡或 HF 住院的复合结局，MRA（P=0.78）或 SGLT2i（P=0.37）的性别间无显著交互作用。纳入了可溶性鸟苷酸环化酶刺激剂和心肌肌球蛋白激活剂等新兴药物治疗的结果，并显示了男性和女性之间一致的治疗效果。
我们的荟萃分析显示，BB 和 ACEI 或 ARB 的治疗效果在性别之间没有差异。对先前发表的关于 MRA、SGLT2i 和新兴疗法的试验进行的综述显示，男性和女性之间的治疗效果一致。
