荷兰格罗宁根大学医学中心Adriaan A Voors团队近日取得一项新成果。他们分析了男性与女性心力衰竭药物的最佳剂量，这是一项前瞻性、观察性的队列研究。相关论文于2019年8月22日在线发表于国际顶尖学术期刊《柳叶刀》。

这项研究招募了11个欧洲国家的心力衰竭患者，包括3539名男性和961名女性，他们的左心室射血分数均低于40%，采用血管紧张素转换酶（ACE）抑制剂或血管紧张素受体阻滞剂（ARBs）和β受体阻滞剂进行治疗，所有患者治疗开始后均存活三个月以上。

在射血分数降低型心力衰竭（HFrEF）的1308名男性和402名女性中，与男性相比，女性年龄更大，体重更轻，身高更矮，但体重指数无显著差异。使用指南推荐目标剂量（ACE）抑制剂或ARBs的男性占25%，和女性（23%）相差不大；使用目标剂量β受体阻滞剂的男性占14%，与女性（13%）相比差异亦不显著。

对于男性来说，使用100%推荐剂量的ACE抑制剂或ARBs和β受体阻滞剂，死亡或因心衰住院的风险最低，但女性在使用推荐剂量的50%时风险降低约30%，进一步提高剂量风险不会降低。在校正了包括年龄和体表面积在内的临床协变量后，这些性别差异仍然存在。ASIAN-HF注册处也观察到了类似的模式，女性使用（ACE）抑制剂或ARBs和β受体阻滞剂推荐剂量的50%，风险降低30%，提高剂量并不会进一步获益。

这项研究表明，与男性相比，女性HFrEF患者可能需要更低剂量的ACE抑制剂或ARBs和β受体阻滞剂，并使人们质疑，对于女性和男性来说，真正最佳的治疗方案究竟是什么。

研究人员表示，相关指南推荐的ACE抑制剂或ARBs和β受体阻滞剂用于治疗HFrEF并未进行严格的性别区分，即使这些药物在药代动力学方面有性别差异。

附：英文原文

Title: Identifying optimal doses of heart failure medications in men compared with women: a prospective, observational, cohort study

Author: Bernadet T Santema, MD;Wouter Ouwerkerk, PhD;Jasper Tromp, MD;Iziah E Sama, PhD;Alice Ravera, MD;Prof Vera Regitz-Zagrosek, MD;Prof Hans Hillege, MD;Prof Nilesh J Samani, FRCP;Prof Faiez Zannad, MD;Prof;Kenneth Dickstein, MD;Prof Chim C Lang, MD;Prof John G Cleland, MD;Jozine M Ter Maaten, MD;Prof Marco Metra, MD;Prof Stefan D Anker, MD;Prof Pim van der Harst, MD;Prof Leong L Ng, MD;Peter van der Meer, MD;Prof Dirk J van Veldhuisen, MD;Sven Meyer, MD;Prof Carolyn S P Lam, MD;on behalf of the ASIAN-HF investigators †Prof Adriaan A Voors, MD

Issue&Volume: 22 August 2019

Summary:

Background

Guideline-recommended doses of angiotensin-converting-enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs), and β blockers are similar for men and women with heart failure with reduced ejection fraction (HFrEF), even though there are known sex differences in pharmacokinetics of these drugs. We hypothesised that there might be sex differences in the optimal dose of ACE inhibitors or ARBs and β blockers in patients with HFrEF.

Methods

We did a post-hoc analysis of BIOSTAT-CHF, a prospective study in 11 European countries of patients with heart failure in whom initiation and up-titration of ACE inhibitors or ARBs and β blockers was encouraged by protocol. We included only patients with left ventricular ejection fraction less than 40%, and excluded those who died within the first 3 months. Primary outcome was a composite of time to all-cause mortality or hospitalisation for heart failure. Findings were validated in ASIAN-HF, an independent cohort of 3539 men and 961 women with HFrEF.

Findings

Among 1308 men and 402 women with HFrEF from BIOSTAT-CHF, women were older (74 [12] years vs 70 [12] years, p<0·0001) and had lower bodyweights (72 [16] kg vs 85 [18] kg, p<0·0001) and heights (162 [7] cm vs 174 [8] cm, p<0·0001) than did men, although body-mass index did not differ significantly. A similar number of men and women reached guideline-recommended target doses of ACE inhibitors or ARBs (99 [25%] vs 304 [23%], p=0·61) and β blockers (57 [14%] vs 168 [13%], p=0·54). In men, the lowest hazards of death or hospitalisation for heart failure occurred at 100% of the recommended dose of ACE inhibitors or ARBs and β blockers, but women showed approximately 30% lower risk at only 50% of the recommended doses, with no further decrease in risk at higher dose levels. These sex differences were still present after adjusting for clinical covariates, including age and body surface area. In the ASIAN-HF registry, similar patterns were observed for both ACE inhibitors or ARBs and β blockers, with women having approximately 30% lower risk at 50% of the recommended doses, with no further benefit at higher dose levels.

Interpretation

This study suggests that women with HFrEF might need lower doses of ACE inhibitors or ARBs and β blockers than men, and brings into question what the true optimal medical therapy is for women versus men.

DOI: https://doi.org/10.1016/S0140-6736(19)31792-1

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31792-1/fulltext#