Long-Term Ambrisentan Therapy for the Treatment of Pulmonary Arterial Hypertension
Long-Term Ambrisentan Therapy for the Treatment of Pulmonary Arterial Hypertension
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DOI：
10.1016/j.jacc.2009.07.033
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发表时间：
2009-11-17
影响因子：
24
通讯作者：
Rubin, Lewis J.
中科院分区：
文献类型：
--
作者：
Oudiz, Ronald J.;Galie, Nazzareno;Rubin, Lewis J.
目的本研究评价安立生坦治疗肺动脉高压（PAH）患者2年的安全性和有效性。白羊座-1（安立生坦治疗肺动脉高压的随机、双盲、安慰剂对照、多中心、疗效研究）和ARIES-2试验是导致安立生坦获得监管批准的关键性12周、安慰剂对照研究方法在ARIES-1和-2研究以及随后的长期扩展方案ARIES-E研究中，383例患者接受安立生坦（2.5、5或10 mg）。疗效和安全性评估是从所有患者的第一剂安贝生坦的基线后data.Results后2年的安贝生坦暴露的时间，从基线的平均变化，在6分钟步行距离改善为5毫克（+23个月; 95%置信区间：9至38个月）和10 mg（+28个月; 95%置信区间：11至45个月）组。联合剂量组1年时的生存率和无临床恶化率估计值分别为94%和83%，2年时分别为88%和72%。转氨酶异常> 3倍正常上限的年化风险与每年2%相似;这些事件大多数是轻度的，不会导致停药。结论：2年的安立生坦治疗与PAH患者运动能力的持续改善和临床恶化和死亡的低风险相关。安立生坦通常耐受良好，在2年研究期间转氨酶异常的风险较低。（一项在完成AMB-320或AMB-321的肺动脉高压受试者中进行的安立生坦长期研究; NCT 00578786）（J Am科尔Cardiol 2009; 54：1971-81）（C）2009，美国心脏病学会基金会
Objectives This study evaluated the safety and efficacy of ambrisentan for a period of 2 years in patients with pulmonary arterial hypertension (PAH).Background Ambrisentan is an oral, once-daily endothelin receptor antagonist that is selective for the endothelin type A receptor. The ARIES-1 (Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Studies) and ARIES-2 trials were the pivotal 12-week, placebo-controlled studies that led to the regulatory approval of ambrisentan (5 and 10 mg) for the treatment of PAH.Methods In the ARIES-1 and -2 studies, and the subsequent long-term extension protocol, the ARIES-E study, 383 patients received ambrisentan (2.5, 5, or 10 mg). Efficacy and safety assessments are presented from the time of the first dose of ambrisentan for all patients with post-baseline data.Results After 2 years of ambrisentan exposure, the mean change from baseline in 6-min walk distance was improved for the 5-mg (+23 m; 95% confidence interval: 9 to 38 m) and 10-mg (+28 m; 95% confidence interval: 11 to 45 m) groups. Estimates of survival and freedom from clinical worsening for the combined dose group were 94% and 83%, respectively, at 1 year and 88% and 72%, respectively, at 2 years. The annualized risk of aminotransferase abnormalities >3x the upper limit of normal was similar to 2% per year; most of these events were mild and did not lead to discontinuation of drug.Conclusions Two years of ambrisentan treatment was associated with sustained improvements in exercise capacity and a low risk of clinical worsening and death in patients with PAH. Ambrisentan was generally well tolerated and had a low risk of aminotransferase abnormalities over the 2-year study period. (A Long Term Study of Ambrisentan in Pulmonary Arterial Hypertension Subjects Having Completed AMB-320 or AMB-321; NCT00578786) (J Am Coll Cardiol 2009; 54: 1971-81) (C) 2009 by the American College of Cardiology Foundation