Macitentan and Morbidity and Mortality in Pulmonary Arterial Hypertension
Macitentan and Morbidity and Mortality in Pulmonary Arterial Hypertension
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DOI：
10.1056/nejmoa1213917
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发表时间：
2013-08-29
影响因子：
158.5
通讯作者：
Simonneau, Gerald
中科院分区：
文献类型：
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作者：
Pulido, Tomas;Adzerikho, Igor;Simonneau, Gerald
背景目前肺动脉高压的治疗方法都是以运动能力为主要终点的短期试验为基础的。我们在一项长期试验中使用发病率和死亡率作为主要终点，评估了马昔腾坦（一种新型双重内皮素受体拮抗剂）的疗效。方法我们随机将有症状的肺动脉高压患者分配接受安慰剂每日一次、马昔腾坦每日一次3 mg剂量，或马昔腾坦每日一次10 mg剂量。在研究入组时，允许稳定使用除内皮素受体拮抗剂以外的口服或吸入治疗肺动脉高压。主要终点是从开始治疗到首次出现死亡、房间隔造口术、肺移植、开始静脉或皮下前列腺素类治疗或肺动脉高压恶化的复合终点的时间。10 mg马昔腾坦剂量为242。主要终点发生率分别为46.4%、38.0%和31.4%。3 mg马昔腾坦剂量与安慰剂相比的风险比为0.70（97.5%置信区间[CI]，0.52至0.96; P=0.01），10 mg马昔腾坦剂量与安慰剂相比的风险比为0.55（97.5% CI，0.39至0.76; P
BackgroundCurrent therapies for pulmonary arterial hypertension have been adopted on the basis of short-term trials with exercise capacity as the primary end point. We assessed the efficacy of macitentan, a new dual endothelin-receptor antagonist, using a primary end point of morbidity and mortality in a long-term trial.MethodsWe randomly assigned patients with symptomatic pulmonary arterial hypertension to receive placebo once daily, macitentan at a once-daily dose of 3 mg, or macitentan at a once-daily dose of 10 mg. Stable use of oral or inhaled therapy for pulmonary arterial hypertension, other than endothelin-receptor antagonists, was allowed at study entry. The primary end point was the time from the initiation of treatment to the first occurrence of a composite end point of death, atrial septostomy, lung transplantation, initiation of treatment with intravenous or subcutaneous prostanoids, or worsening of pulmonary arterial hypertension.ResultsA total of 250 patients were randomly assigned to placebo, 250 to the 3-mg macitentan dose, and 242 to the 10-mg macitentan dose. The primary end point occurred in 46.4%, 38.0%, and 31.4% of the patients in these groups, respectively. The hazard ratio for the 3-mg macitentan dose as compared with placebo was 0.70 (97.5% confidence interval [CI], 0.52 to 0.96; P=0.01), and the hazard ratio for the 10-mg macitentan dose as compared with placebo was 0.55 (97.5% CI, 0.39 to 0.76; P