Comparison of omapatrilat chronic and enalapril in patients with heart failure - The omapatrilat versus enalapril randomized trial of utility in reducing events (OVERTURE)
Comparison of omapatrilat chronic and enalapril in patients with heart failure - The omapatrilat versus enalapril randomized trial of utility in reducing events (OVERTURE)
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DOI：
10.1161/01.cir.0000029801.86489.50
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发表时间：
2002-08-20
期刊：
影响因子：
37.8
通讯作者：
Swedberg, K
中科院分区：
文献类型：
--
作者：
Packer, M;Califf, RM;Swedberg, K
背景-联合抑制血管紧张素转换酶（ACE）和中性内肽酶（NEP）可能比单独抑制ACE对心力衰竭产生更大的益处。方法和结果-我们随机将5770例纽约心脏协会II至IV级心力衰竭患者分为两组，一组用ACE抑制剂依那普利，另一组用依那普利，（10 mg BID，n=2884）或ACE-NEP抑制剂omapatrilat（40 mg每日一次，n=2886），平均14.5个月。主要终点-死亡或因需要静脉治疗的心力衰竭住院的综合风险-被前瞻性地用于检验优效性和非劣效性假设（基于依那普利在左心室功能不全研究[SOLVD]治疗试验中的作用）。依那普利组有973例患者达到主要终点，奥马曲拉组有914例患者达到主要终点（风险比0.94; 95% CI：0.86 - 1.03，P=0.187）-符合非劣效性但不符合优效性的预定标准，Omapatrilat组的心血管死亡或住院风险降低9%（P=0.024），死亡风险降低6%（P=0.339）。在SOLVD治疗试验（其中包括所有的心力衰竭住院治疗）中使用的定义的主要终点的事后分析显示，与omapatrilat（名义P=0.012）治疗的患者的风险降低了11%，结论omapatrilat降低慢性心力衰竭的死亡和住院治疗的风险，但在降低主要临床事件的风险方面并不比单独使用ACE抑制剂更有效。在次要和事后分析中观察到的支持omapatrilat的组间差异值得进一步研究。
Background-Combined inhibition of the angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) may produce greater benefits in heart failure than ACE inhibition alone.Methods and Results-We randomly assigned 5770 patients with New York Heart Association class II to IV heart failure to double-blind treatment with either the ACE inhibitor enalapril (10 mg BID, n=2884) or to the ACE-NEP inhibitor omapatrilat (40 mg once daily, n=2886) for a mean of 14.5 months. The primary end point-the combined risk of death or hospitalization for heart failure requiring intravenous treatment-was used prospectively to test both a superiority and noninferiority hypothesis (based on the effect of enalapril in the Studies of Left Ventricular Dysfunction [SOLVD] Treatment Trial). A primary end point was achieved in 973 patients in the enalapril group and in 914 patients in the omapatrilat group (hazard ratio 0.94; 95% CI: 0.86 to 1.03, P=0.187)-a result that fulfilled prespecified criteria for noninferiority but not for superiority, The omapatrilat group also had a 9% lower risk of cardiovascular death or hospitalization (P=0.024) and a 6% lower risk of death (P=0.339). Post hoc analysis of the primary end point with the definition used in the SOLVD Treatment Trial (which included all hospitalizations for heart failure) showed an 11% lower risk in patients treated with omapatrilat (nominal P=0.012).Conclusion-Omapatrilat reduces the risk of death and hospitalization in chronic heart failure but was not more effective than ACE inhibition alone in reducing the risk of a primary clinical event. Between-group differences in favor of omapatrilat observed in secondary and post hoc analyses warrant further study.