安立生坦治疗肺高压的疗效及临床安全性：来自5项随机双盲安慰剂对照临床试验的493名患者的荟萃分析

The Efficiency and Clinical Adverse Effects of Ambrisentan for Pulmonary Hypertension: Insights from the Meta-Analysis of 493 Patients from 5 Randomized Double-Blind Placebo-Controlled Clinical Trials

摘要: 目的：安立生坦是一种高选择性的内皮素受体拮抗剂，已广泛应用于肺高压(pulmonary hypertension, PH)，但临床不良反应和疗效报道有限，主要来源于个体试验，因此，我们进行了荟萃分析，观察安立生坦的疗效及安全性。方法：系统检索PubMed、Embase、Cochrane数据库和clintrials.gov网站后，纳入至少1个试验组接受安立生坦治疗的随机对照试验(randomized controlled trials, RCTs)。评价安立生坦的临床不良事件(adverse events, AEs)和疗效。根据研究间的异质性，使用随机或固定效应模型。结果：共纳入5项临床随机对照研究493例患者。在平均24周的随访中，安立生坦组6分钟步行距离(6-min walk distance, 6MWD)增加了37.53米，减少临床恶化、血浆B型利钠肽(B-type natriuretic peptide, BNP)浓度降低。安立生坦组外周水肿(18.94% vs 7.91%; RR = 1.58, 95% CI 1.01~2.45, P = 0.04)和鼻塞(7.34% vs 2.04%; RR = 3.25, 95% CI 1.08~9.79, P = 0.04)的发生率显著高于安慰剂组。安立生坦组没有发现其他副反应发生率显著升高。结论：安立生坦能显著提高PH患者的运动耐力，减少临床恶化，而不良反应无明显增加。

Abstract: Objective: Ambrisentan, a highly selective endothelin receptor antagonist (ERA), has been widely applied in patients with pulmonary hypertension (PH). It is necessary to evaluate the clinical effects and adverse reaction of ambrisentan in PH. Methods: After systematic searches of PubMed, Embase, Cochrane Library and the Clinical Trials.gov website, randomized controlled trials (RCTs) with patients receiving ambrisentan in at least 1 treatment group were included. The clinical adverse events (AEs) and the efficiency of ambrisentan were evaluated. Summary relative risks and 95% CIs were calculated using random- or fixed-effects models according to between-study heterogeneity. Results: In total, 5 randomized trials including 493 patients met the inclusion criteria. At an average follow-up of 24 weeks, the ambrisentan group had increased 37.53 m in 6-min walk distance (6MWD), decreased clinical worsening, and decreased plasma B-type natriuretic peptide (BNP) concentration. Meta-analysis showed that the incidence of peripheral edema (18.94% versus 7.91%; RR 1.58, 95% CI 1.01~2.45, P = 0.04), and nasal congestion (7.34% versus 2.04%; RR 3.25, 95% CI 1.08~9.79, P = 0.04) was significantly higher in the ambrisentan group compared with placebo. Ambrisentan was not found to increase other reported AEs compared with placebo. Conclusions: Ambrisentan in PH is well established and still requires clinical trials for an identification of its efficiency on PH patients for an optimized period lessening a serious complication and the common AEs.