波生坦一线治疗特发性肺动脉高压的临床效果及安全性评价

Evaluation of clinical efficacy and safety of first-line bosentan therapy for idiopathic pulmonary hypertension

目的通过对特发性肺动脉高压(IPAH)患者口服波生坦作为一线治疗进行开放性研究,评价波生坦治疗IPAH的临床效果及安全性。方法回顾性分析2008年3月-2009年12月期间在北京世纪坛医院住院的应用口服波生坦作为一线治疗的13例IPAH患者的临床资料,分析治疗前后6min步行距离(6MWD)、血流动力学指标、氨基末端B型利钠肽前体(NT-proBNP)含量、血常规、肝肾功能的变化。结果 13例IPAH患者均为女性,年龄16～39(28.46±8.06)岁,首次症状出现至确诊时间为15～41(31.16±9.35)个月。经过16周波生坦治疗,平均肺动脉压、肺循环阻力、右心房压均有不同程度降低,分别从治疗前的69.67±17.11、21.25±4.00、9.71±2.61mmHg降低至治疗后的58.00±10.22、18.98±3.21、6.67±4.18mmHg(P<0.05)。心指数和6WMD提高(治疗前2.24±0.62和318.23±73.17m,治疗后2.87±1.13和412.20±54.23m,P<0.05),NT-proBNP明显下降(治疗前3432.17±834.15pg/ml,治疗后1935.26±986.05pg/ml,P<0.05)。与治疗前比较,治疗后患者血常规及肝肾功能均无明显变化。结论口服波生坦一线治疗IPAH能够明显改善患者的运动能力和血流动力学指标,从而提高生存质量,延缓疾病恶化。

Objective To evaluate the efficacy and safety of bosentan as the first-line therapy in an open-label study of patients with idiopathic pulmonary arterial hypertension （IPAH）. Methods Thirteen inpatients with IPAH were consecutively enrolled in the open-label study from Mar. 2008 to Dec. 2009 in Beijing Shijitan Hospital. Bosentan was prescribed as the first-line therapy in addition to routine treatment, initiating from 62. 5rag bid for 4 weeks, followed by a boost to 125mg bid for 12 weeks. All the patients were at level III and IV on WHO Function Classification of IPAH before treatment, and their clinical features were collected. Six-minute walking distance checks （6MWD）, hemodynamic indexes, blood level of N terminal pro-Prtype natriuretic peptide （NT-proBNP）, routine blood tests and blood biochemical changes were analyzed before and after treatment. Results All the 13 patients with IPAH were females, 16-39 yrs （28. 46± 8. 06） of age, with a mean time of 31.16±9.35 （15-41） months from initial appearance of symptoms to final diagnosis. After 16 week treatment, mean pulmonary artery pressure （mPAP）, pulmonary vascular resistance （PVR） and right atrial pressure （RAP） declined significantly as compared with baseline data （69. 67±17. 11 vs 58. 00±10. 22mmHg, P〈0.05; 21.25±4.00 vs 18. 98±3.21mmHg, P〈 0.05; 9. 71±2. 61 vs 6. 67±4. 18mmHg, P〈0. 05; respectively）, cardiac index （CI） was improved from 2. 24±0. 62 to 2. 87±1.13 （P〈 0. 05） and 6MWD from 2. 87 ± 1. 13m to 412. 20 ± 54. 23m （P〈0. 05）, while NT-proBNP decreased significantly （from 3432. 17 ±834. 15pg/ml to 1935. 26±986. 05pg/ml, P〈0. 05）. Ecbocardiograms revealed that the pericardial effusion found in 3 patients disappeared after treatment. Bosentan was well tolerated and caused no significant adverse events in liver function. Conclusion Patients with IPAH may be benefited by oral administration of bosentan as the first-line therapy, which dramatically improves the hemodynamics and motor ability of patients, thereby enhances the quality of life and delays deterioration of the disease.