安立生坦单药治疗肺动脉高压患者的长期疗效观察

Long-term effects with ambrisentan monotherapy in patients with pulmonary arterial hypertension

目的 研究高选择性内皮素A型受体拮抗剂安立生坦治疗中国成人肺动脉高压患者的长期疗效和安全性.方法 入选2011年7月至2012年8月期间接受安立生坦2.5或5 mg每日1次、口服至少6个月的肺动脉高压患者.主要疗效终点为安立生坦治疗前后运动耐量,WHO肺动脉高压功能分级,血浆N末端B型利钠肽原（NT-proBNP）水平,和超声心动图参数变化情况.患者服用安立生坦的安全性和耐受性通过不良事件的发生率和严重程度进行评估.结果 共计纳入18例肺动脉高压患者,平均年龄（39 ± 17）岁,女性患者8例（55.6％）,WHO肺动脉高压功能分级Ⅲ级患者11例（61.1％）.安立生坦单药治疗中位时间为17个月（6 ～ 26个月）.治疗后患者6 min步行距离由平均（400±91）m增加至（495±97）m（P＜0.001）;NT-proBNP由中位数308 （53～1 645） ng/L下降至80 （22 ～454） ng/L（P =0.005）;超声心动图估测肺动脉收缩压由平均（82±41） mmHg（1 mmHg二0.133 kPa）下降至（62 ± 30） mmHg（P=0.001）,左心室舒张末期内径由平均（40± 6） mm增加至（44±6） mm （P＜0.004）;11例（61.1％）患者WHO肺动脉高压功能分级较基线时改善,7例（38.9％）无变化.研究期间,无患者死亡或因发生严重不良反应而退出研究.结论 长期安立生坦单药治疗可有效改善中国肺动脉高压患者的运动耐量、WHO肺动脉高压功能分级,降低肺动脉收缩压和NT-proBNP水平,并且安全性和耐受性良好.

Objective To investigate long-term efficacy and safety of ambrisentan monotherapy in patients with pulmonary arterial hypertension （PAH）.Methods Patients with PAH who received 2.5 mg or 5 mg of ambrisentan once daily between July 10,2011 and August 30,2012 for at least 6 months were enrolled.The efficacy endpoints were change in exercise capacity,World Health Organization （WHO） functional class and N-terminal pro-brain natriuretic peptide （NT-proBNP） level,echocardiographic parameters.The safety endpoint was the safety of long-term ambrisentan administration,as defined by the incidence and severity of adverse events.Results A total of 18 patients with PAH were enrolled.Mean age was （39 ± 17） years,8 （55.6%） were female,and 11 （61.1%） patients were in WHO functional class Ⅲ.The median duration of treatment was 17 months （range：6-26 months）.After treatment,the 6MWD was significantly increased[（495 ±97） m vs.（400 ±91） m,P 〈0.001],NT-proBNP was significantly reduced [308 （53-1 645） ng/L vs.80 （22-454） ng/L,P =0.005],the systolic pulmonary artery was significantly decreased [（62 ± 30） mmHg vs.（82 ± 41） mmHg,P =0.001] and left ventricular end diastolic diameter was significantly increased [（44 ± 6） mm vs.（40 ± 6） mm,P 〈 0.004] compared to pre-treatment.WHO functional class was improved compared with baseline in 11 （61.1%） patients,stable in 7（38.9%） patients.No patient died during the treatment period.No patient was withdrawn from this study for safety reasons.Conclusions Long-term treatment of ambrisentan can effectively improve the exercise capacity,reduce systolic pulmonary artery pressure and NT-proBNP in PAH patients.Ambrisentan is safe and well tolerated in Chinese PAH patients.