Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension
Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension
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DOI：
10.1056/nejmoa1413687
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发表时间：
2015-08-27
影响因子：
158.5
通讯作者：
Rubin, L. J.
中科院分区：
文献类型：
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作者：
Galie, N.;Barbera, J. A.;Rubin, L. J.
研究背景关于安立生坦和他达拉非初始联合治疗对肺动脉高压患者长期预后影响的数据很少。1比率，患有世界卫生组织肺动脉高压功能分级II级或III级症状且既往未接受过初始联合治疗的受试者10 mg安立生坦加40 mg他达拉非（联合治疗组）、10 mg安立生坦加安慰剂（安立生坦单药治疗组）或40 mg他达拉非加安慰剂（他达拉非单药治疗组），均每日给药一次。时间-事件分析的主要终点是首次临床失败事件，其定义为首次发生死亡、因肺动脉高压恶化住院、疾病进展或不满意的长期临床反应的复合事件。253例被分配到联合治疗组，126例被分配到安立生坦单药治疗组，121例被分配到他达拉非单药治疗组。主要终点事件分别发生在这些组的18%、34%和28%的参与者中，而合并单药治疗组（两个单药治疗组合并）的发生率为31%。联合治疗组与合并单药治疗组主要终点的风险比为0.50（95%可信区间[CI]，0.35 - 0.72; P
BACKGROUNDData on the effect of initial combination therapy with ambrisentan and tadalafil on long-term outcomes in patients with pulmonary arterial hypertension are scarce.METHODSIn this event-driven, double-blind study, we randomly assigned, in a 2: 1: 1 ratio, participants with World Health Organization functional class II or III symptoms of pulmonary arterial hypertension who had not previously received treatment to receive initial combination therapy with 10 mg of ambrisentan plus 40 mg of tadalafil (combination-therapy group), 10 mg of ambrisentan plus placebo (ambrisentan-monotherapy group), or 40 mg of tadalafil plus placebo (tadalafil-monotherapy group), all administered once daily. The primary end point in a time-to-event analysis was the first event of clinical failure, which was defined as the first occurrence of a composite of death, hospitalization for worsening pulmonary arterial hypertension, disease progression, or unsatisfactory long-term clinical response.RESULTSThe primary analysis included 500 participants; 253 were assigned to the combination-therapy group, 126 to the ambrisentan-monotherapy group, and 121 to the tadalafil-monotherapy group. A primary end-point event occurred in 18%, 34%, and 28% of the participants in these groups, respectively, and in 31% of the pooled-monotherapy group (the two monotherapy groups combined). The hazard ratio for the primary end point in the combination-therapy group versus the pooled-monotherapy group was 0.50 (95% confidence interval [CI], 0.35 to 0.72; P