波生坦治疗特发性肺动脉高压患者的疗效及安全性

The efficacy and safety of bosentan therapy for Chinese patients with idiopathic pnlmonary arterial hypertension： an open-label, prospective multicenter study

目的 观察内皮素受体拮抗剂波生坦治疗中国特发性肺动脉高压患者的有效性、安全性及耐受性。方法 全国多中心Ⅳ期临床试验，共入选79例右心导管等技术确诊的新发特发性肺动脉高压患者，口服波生坦每日2次，每次62．5mg，治疗4周后增至每日2次，每次125mg至16周试验结束。分别在基线及治疗16周时记录6分钟步行距离，WHO肺高压功能分级、Borg呼吸困难评分及超声心动图评价资料。结果 波生坦治疗16周后，患者6分钟步行距离从（343．7±93．7）m增至（397．5±104．4）m（P〈0．01），WHO肺高压功能分级显著改善（P〈0．01），Borg呼吸困难评分由3．0±1．5降低至2．5±1．5（P〈0．01），超声心动图估测肺动脉收缩压从（97．8±25．2）mmHg（1mmHg=0．133kPa）下降至（92．8±29．5）mmHg（P〈0．05）。无患者因无法耐受不良反应退出。结论 波生坦能显著改善中国特发性肺动脉高压患者的运动耐量、心功能，且具有良好的安全性和耐受性。

Objective To investigate the efficacy, safety and tolerance of bosentan, a dual endothelin receptor antagonist, in Chinese patients with idiopathic pulmonary arterial hypertension （IPAH）. Methods Totally 79 IPAH patients （hemodynamic criteria confirmed by right heart catheterization） were included in this open-label, prospective multicenter study. Patients received 62. 5 mg of bosentan twice daily for the first 4 weeks, and then up-titrated to 125 mg twice daily for another 12 weeks. The primary end point was the change in exercise capacity showed by six-minute walk distance （6MWD） from baseline to 16 weeks. Secondary end points included the change in World Health Organization （WHO） functional class, Borg dyspnoea scale and systolic pulmonary artery pressure measured by echocardiography. Results The 6MWD increased from （343.7±93.7） meters at baseline to （397. 5±104.4） meters after 16 weeks （P 〈 0. 01 ）, WHO functional class and Borg dyspnoea scale were also significantly improved after 16 weeks therapy compared to baseline levels （ all P 〈 0.01 ）. Furthermore, the systolic pulmonary artery pressure was significantly decreased from （97. 8 ±25.2） mm Hg （ 1 mm Hg = 0. 133 kPa） to （92. 8±29.5 ） mm Hg （ P 〈 0. 05 ） after 16 weeks bosentan treatment. There was no patient withdrawal from this study for safety consideration. Conclusion Bosentan therapy is well tolerated and can improve the exercise capacity and WHO functional class in Chinese IPAH patients.