Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial
Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial
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DOI：
10.1016/s0140-6736(09)61913-9
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发表时间：
2009-11-01
期刊：
影响因子：
168.9
通讯作者：
Poole-Wilson, Philip A.
中科院分区：
文献类型：
--
作者：
Konstam, Marvin A.;Neaton, James D.;Poole-Wilson, Philip A.
背景血管紧张素受体阻滞剂（ARB）是心力衰竭患者的有效治疗方法，但剂量与临床结果之间的关系尚未探讨。我们比较了高剂量与低剂量氯沙坦对心力衰竭患者临床结局的影响。 方法 这项双盲试验在 30 个国家的 255 个地点进行。 3846 名患有纽约心脏协会 II-IV 级心力衰竭、左心室射血分数 40% 或更低且对血管紧张素转换酶 (ACE) 抑制剂不耐受的患者被随机分配至每日服用氯沙坦 150 mg（n=1927）或 50 mg（n=1919）。分配是通过中心和是否存在P-阻滞剂治疗分层的区组随机化，并且所有患者和研究人员都对分配情况不知情。主要终点是死亡或因心力衰竭入院。分析是按意向治疗进行的。这项研究已在 ClinicalTrials.gov 注册，编号为 NCT00090259。 结果 由于数据质量较差，每组中都有 6 名患者被排除在外。每组中位随访时间为 4.7 年（氯沙坦 150 mg 的 IQR 为 3.7-5.5；氯沙坦 50 mg 的 IQR 为 3.4-5.5），150 mg 组有 828 名患者 (43%)，而 50 环组有 889 名患者 (46%) 死亡或因心力衰竭入院（风险比 [HR] 0.90，95% CI） 0.82-0.99； p=0.027）。对于两个主要终点组成部分，150 mg 组有 635 名患者死亡，而 50 环组有 665 名患者死亡（HR 0.94，95% CI 0.84-1.04；p=0.24），分别有 450 名患者和 503 名患者因心力衰竭入院（0.87，0.76-0.98；p=0.025）。肾功能损害（n=454 vs 317）、低血压（203 vs 145）和高钾血症（195 vs 131）在 150 mg 组中比 50 mg 组更常见，但这些不良事件并没有导致 150 mg 组明显更多的治疗中断。 与每天服用氯沙坦 50 环相比，出现心力衰竭、左心室射血分数降低以及对 ACE 抑制剂不耐受。这些发现显示了增加 ARB 剂量以带来临床益处的价值。
Background Angiotensin-receptor blockers (ARBs) are effective treatments for patients with heart failure, but the relation between dose and clinical outcomes has not been explored. We compared the effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure.Methods This double-blind trial was undertaken in 255 sites in 30 countries. 3846 patients with heart failure of New York Heart Association class II-IV, left-ventricular ejection fraction 40% or less, and intolerance to angiotensin-converting-enzyme (ACE) inhibitors were randomly assigned to losartan 150 mg (n=1927) or 50 mg daily (n=1919). Allocation was by block randomisation stratified by Centre and presence or absence of P-blocker therapy, and all patients and investigators were masked to assignment. The primary endpoint was death or admission for heart failure. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00090259.Findings Six patients in each group were excluded because of poor data quality. With 4.7-year median follow-up in each group (IQR 3.7-5.5 for losartan 150 mg; 3.4-5.5 for losartan 50 mg), 828 (43%) patients in the 150 mg group versus 889 (46%) in the 50 ring group died or were admitted for heart failure (hazard ratio [HR] 0.90, 95% CI 0.82-0.99; p=0.027). For the two primary endpoint components, 635 patients in the 150 mg group versus 665 in the 50 ring group died (HR 0.94, 95% CI 0.84-1.04; p=0.24), and 450 versus 503 patients were admitted for heart failure (0.87,0.76-0.98; p=0.025). Renal impairment (n=454 vs 317), hypotension (203 vs 145), and hyperkalaemia (195 vs 131) were more common in the 150 mg group than in the 50 mg group, but these adverse events did not lead to significantly more treatment discontinuations in the 150 mg group.Interpretation Losartan 150 mg daily reduced the rate of death or admission for heart failure in patients with heart failure, reduced left-ventricular ejection fraction, and intolerance to ACE inhibitors compared with losartan 50 ring daily. These findings show the value of up-titrating ARB doses to confer clinical benefit.