Rouleau J L, Pfeffer M A, Stewart D J, Isaac D, Sestier F, Kerut E K, Porter C B, Proulx G, Qian C, Block A J
Division of Cardiology, Toronto General Hospital, University of Toronto, ON, Canada.
Lancet. 2000 Aug 19;356(9230):615-20. doi: 10.1016/s0140-6736(00)02602-7.
We aimed to assess in patients with congestive heart failure whether dual inhibition of neutral endopeptidase and angiotensin-converting enzyme (ACE) with the vasopeptidase inhibitor omapatrilat is better than ACE inhibition alone with lisinopril on functional capacity and clinical outcome.
We did a prospective, randomised, double-blind, parallel trial of 573 patients with New York Heart Association (NYHA) class II-IV congestive heart failure, left-ventricular ejection fraction of 40% or less, and receiving an ACE inhibitor. Patients were randomly assigned omapatrilat at a daily target dose of 40 mg (n=289) or lisinopril at a daily target dose of 20 mg (n=284) for 24 weeks. The primary endpoint was improvement in maximum exercise treadmill test (ETT) at week 12. Secondary endpoints included death and comorbid events indicative of worsening heart failure.
Week 12 ETT increased similarly in the omapatrilat and lisinopril groups (24 vs 31 s, p=0.45). The two drugs were fairly well tolerated, but there were fewer cardiovascular-system serious adverse events in the omapatrilat group than in the lisinopril group (20 [7%] vs 34 [12%], p=0.04). There was a suggestive trend in favour of omapatrilat on the combined endpoint of death or admission for worsening heart failure (p=0.052; hazard ratio 0.53 [95% CI 0.27-1.02]) and a significant benefit of omapatrilat in the composite of death, admission, or discontinuation of study treatment for worsening heart failure (p=0.035; 0.52 [0.28-0.96]). Omapatrilat improved NYHA class more than lisinopril in patients who had NYHA class III and IV (p=0.035), but not if patients with NYHA class II were included.
Our findings suggest that omapatrilat could have some advantages over lisinopril in the treatment of patients with congestive heart failure. Thus use of vasopeptidase inhibitors could constitute a potentially important treatment for further improving the prognosis and well being of patients with this disorder.
我们旨在评估在充血性心力衰竭患者中，血管肽酶抑制剂奥马曲拉对中性内肽酶和血管紧张素转换酶（ACE）的双重抑制作用是否优于单独使用赖诺普利抑制ACE对功能能力和临床结局的影响。
我们对573例纽约心脏协会（NYHA）心功能II-IV级的充血性心力衰竭患者进行了一项前瞻性、随机、双盲、平行试验，这些患者左心室射血分数为40%或更低，且正在接受ACE抑制剂治疗。患者被随机分配接受每日目标剂量40mg的奥马曲拉（n=289）或每日目标剂量20mg的赖诺普利（n=284），治疗24周。主要终点是第12周时最大运动平板试验（ETT）的改善情况。次要终点包括死亡和提示心力衰竭恶化的合并事件。
奥马曲拉组和赖诺普利组第12周的ETT增加情况相似（分别增加24秒和31秒，p=0.45）。两种药物的耐受性都相当好，但奥马曲拉组的心血管系统严重不良事件比赖诺普利组少（20例[7%]对34例[12%]，p=0.04）。在死亡或因心力衰竭恶化入院的联合终点上，有倾向于奥马曲拉的趋势（p=0.052；风险比0.53[95%CI 0.27-1.02]），且在死亡、入院或因心力衰竭恶化而停止研究治疗的综合情况方面，奥马曲拉有显著益处（p=0.035；0.52[0.28-0.96]）。在NYHA心功能III级和IV级的患者中，奥马曲拉比赖诺普利更能改善NYHA分级（p=0.035），但如果纳入NYHA心功能II级的患者则不然。
我们的研究结果表明，在治疗充血性心力衰竭患者方面，奥马曲拉可能比赖诺普利有一些优势。因此，使用血管肽酶抑制剂可能是进一步改善这种疾病患者预后和健康状况的一种潜在重要治疗方法。
