Identifying optimal doses of heart failure medications in men compared with women: a prospective, observational, cohort study
Identifying optimal doses of heart failure medications in men compared with women: a prospective, observational, cohort study
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DOI：
10.1016/s0140-6736(19)31792-1
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发表时间：
2019-10-05
期刊：
影响因子：
168.9
通讯作者：
Voors, Adriaan A.
中科院分区：
文献类型：
--
作者：
Santema, Bernadet T.;Ouwerkerk, Wouter;Voors, Adriaan A.
背景指南-血管紧张素转换酶(ACE)抑制剂或血管紧张素受体阻滞剂(ARB)和β受体阻滞剂对射血分数(HFrEF)降低的心力衰竭患者的推荐剂量相似，尽管这些药物的药代动力学存在已知的性别差异。我们假设在HFrEF患者中，ACE抑制剂或ARB和β受体阻滞剂的最佳剂量可能存在性别差异。方法我们对BioStat-CHF进行了一项特别后分析，这是一项在11个欧洲国家进行的前瞻性研究，研究对象是心力衰竭患者，方案鼓励启动和上调ACE抑制剂或ARB和β受体阻滞剂。我们只包括左心室射血分数低于40%的患者，并排除那些在前3个月内死亡的患者。主要结果是所有原因死亡或因心力衰竭住院的时间的综合结果。来自BioStat-CHF的1308名男性和402名女性HFrEF患者中，女性年龄较大(74[12]岁vs70[12]岁，p<；0.0001)，体重(72[16]kg vs85[18]kg，p<；0.0001)和身高(162[7]cm vs174[8]cm，p<；0.0001)比男性低。达到指南推荐的血管紧张素转换酶抑制剂或ARB(99[25%]比304[23%]，p=0.61)和β受体阻滞剂(57[14%]比168[13%]，p=0.54)目标剂量的男性和女性相似。在男性中，因心力衰竭而死亡或住院的风险最低的是ACE抑制剂或ARB和β受体阻滞剂推荐剂量的100%，而女性仅在推荐剂量的50%时风险降低约30%，高剂量水平的风险不会进一步降低。在调整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。在亚洲心力衰竭登记中，观察到ACE抑制剂或ARB和β受体阻滞剂的相似模式，女性在50%的推荐量时风险降低约30%，而高剂量水平则没有进一步的益处。这项研究表明，患有HFrEF的女性可能需要比男性更低剂量的ACE抑制剂或ARB和β受体阻滞剂，这让人质疑女性与男性真正的最佳药物治疗是什么。版权所有(C)2019爱思唯尔有限公司。保留所有权利。
Background Guideline-recommended doses of angiotensin-converting-enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs), and beta 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 beta 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 beta 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 beta 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 beta 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 beta 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 beta blockers than men, and brings into question what the true optimal medical therapy is for women versus men. Copyright (C) 2019 Elsevier Ltd. All rights reserved.