Galiè Nazzareno, Olschewski Horst, Oudiz Ronald J, Torres Fernando, Frost Adaani, Ghofrani Hossein A, Badesch David B, McGoon Michael D, McLaughlin Vallerie V, Roecker Ellen B, Gerber Michael J, Dufton Christopher, Wiens Brian L, Rubin Lewis J
Institute of Cardiology, University of Bologna, Via Massarenti, 9, 40138-Bologna, Italy.
Circulation. 2008 Jun 10;117(23):3010-9. doi: 10.1161/CIRCULATIONAHA.107.742510. Epub 2008 May 27.
Ambrisentan is a propanoic acid-based, A-selective endothelin receptor antagonist for the once-daily treatment of pulmonary arterial hypertension.
Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Study 1 and 2 (ARIES-1 and ARIES-2) were concurrent, double-blind, placebo-controlled studies that randomized 202 and 192 patients with pulmonary arterial hypertension, respectively, to placebo or ambrisentan (ARIES-1, 5 or 10 mg; ARIES-2, 2.5 or 5 mg) orally once daily for 12 weeks. The primary end point for each study was change in 6-minute walk distance from baseline to week 12. Clinical worsening, World Health Organization functional class, Short Form-36 Health Survey score, Borg dyspnea score, and B-type natriuretic peptide plasma concentrations also were assessed. In addition, a long-term extension study was performed. The 6-minute walk distance increased in all ambrisentan groups; mean placebo-corrected treatment effects were 31 m (P=0.008) and 51 m (P<0.001) in ARIES-1 for 5 and 10 mg ambrisentan, respectively, and 32 m (P=0.022) and 59 m (P<0.001) in ARIES-2 for 2.5 and 5 mg ambrisentan, respectively. Improvements in time to clinical worsening (ARIES-2), World Health Organization functional class (ARIES-1), Short Form-36 score (ARIES-2), Borg dyspnea score (both studies), and B-type natriuretic peptide (both studies) were observed. No patient treated with ambrisentan developed aminotransferase concentrations >3 times the upper limit of normal. In 280 patients completing 48 weeks of treatment with ambrisentan monotherapy, the improvement from baseline in 6-minute walk at 48 weeks was 39 m.
Ambrisentan improves exercise capacity in patients with pulmonary arterial hypertension. Improvements were observed for several secondary end points in each of the studies, although statistical significance was more variable. Ambrisentan is well tolerated and is associated with a low risk of aminotransferase abnormalities.
安立生坦是一种基于丙酸的、A 选择性内皮素受体拮抗剂，用于每日一次治疗肺动脉高压。
肺动脉高压患者使用安立生坦的随机、双盲、安慰剂对照、多中心疗效研究 1 和 2（ARIES - 1 和 ARIES - 2）是同期进行的双盲、安慰剂对照研究，分别将 202 例和 192 例肺动脉高压患者随机分为安慰剂组或安立生坦组（ARIES - 1 为 5 或 10 mg；ARIES - 2 为 2.5 或 5 mg），每日口服一次，共 12 周。每项研究的主要终点是从基线到第 12 周 6 分钟步行距离的变化。还评估了临床恶化情况、世界卫生组织功能分级、简明健康状况调查 36 项评分、Borg 呼吸困难评分以及 B 型利钠肽血浆浓度。此外，进行了一项长期扩展研究。所有安立生坦组的 6 分钟步行距离均增加；在 ARIES - 1 中，5 mg 和 10 mg 安立生坦的平均安慰剂校正治疗效果分别为 31 m（P = 0.008）和 51 m（P < 0.001），在 ARIES - 2 中，2.5 mg 和 5 mg 安立生坦的平均安慰剂校正治疗效果分别为 32 m（P = 0.022）和 59 m（P < 0.001）。观察到临床恶化时间（ARIES - 2）、世界卫生组织功能分级（ARIES - 1）、简明健康状况调查 36 项评分（ARIES - 2）、Borg 呼吸困难评分（两项研究）以及 B 型利钠肽（两项研究）均有改善。接受安立生坦治疗的患者中，无一例出现转氨酶浓度超过正常上限 3 倍的情况。在 280 例完成 48 周安立生坦单药治疗的患者中，48 周时 6 分钟步行距离较基线的改善为 39 m。
安立生坦可改善肺动脉高压患者的运动能力。在每项研究中，几个次要终点均有改善，尽管统计学显著性变化更大。安立生坦耐受性良好，且转氨酶异常风险较低。
