法舒地尔联合西地那非治疗慢性阻塞性肺疾病合并肺动脉高压的疗效研究

Efficacy and safety of fasudil combined with sildenafil in the treatment of chronic obstructive pulmonary disease with pulmonary hypertension

目的探讨法舒地尔联合西地那非治疗慢性阻塞性肺疾病合并肺动脉高压(COPD-PAH)的疗效和安全性。方法 2016年3月至2018年5月在该院呼吸内科病房选取90例COPD-PAH患者,按照分层区组随机化原则分为观察组(45例)和对照组(45例)。对照组患者给予常规治疗+西地那非,观察组给予给予常规治疗+西地那非+法舒地尔,连用14d。治疗前后比较两组患者的血流动力学[肺动脉收缩压(PASP)、平均肺动脉压(mPAP)、三尖瓣反流速度(TRV)、右室流出道内径(RVOT)、Tei指数、左室射血分数(LVEF)]、血气分析[血氧分压(PaO_2)及二氧化碳分压(PaCO_2)]、血管活性因子[内皮素-1(ET-1)、一氧化氮(NO)、血管内皮生长因子(VEGF)]水平及运动耐力[6min步行距离(6MWD)]的变化,评价临床疗效,统计药物的不良反应。结果治疗14d后,观察组的总有效率高于对照组(P=0.012);两组患者的血流动力学(PASP、mPAP、TRV、RVOT、Tei指数、LVEF),血气分析(PaO_2、PaCO_2),血管活性因子(ET-1、NO、VEGF),6MWD均较治疗前有明显改善(P<0.01),而观察组改善更明显(P<0.05);两组患者的药物不良反应发生率比较差异无统计学意义(χ2=0.809,P=0.368)。结论法舒地尔联合西地那非能安全有效降低COPD-PAH患者的肺动脉压力,其作用机制可能与降低血清ET-1、VEGF水平,升高血清NO水平有关。

Objective To study the efficacy and safety of fasudil combined with sildenafil in the treatment of chronic obstructive pulmonary disease with pulmonary hypertension(COPD-PAH).Methods From March 2016 to May 2018,90 patients with COPD-PAH in our hospital were divided into two group according to randomized complete blocks designs:the control group(n=45)and the observation group(n=45).The control group received routine treatment+sildenafil while the observation group received routine treatment+sildenafil+fasudil,continuously for 14 days.Hemodynamics [pulmonary artery systolic pressure(PASP),mean pulmonary artery pressure(mPAP),tricuspid regurgitation velocity(TRV),right ventricular outflow tract diameter(RVOT)and Tei index,left ventricular ejection fraction(LVEF)],blood gas analysis[partial pressure of oxygen(PaO2)and partial pressure of carbon dioxide(PaCO2)],vasoactive factor[endothelin-1(ET-1),nitric oxide(NO),vascular endothelial growth factor(VEGF)]and exercise endurance[6 min walking distance(6 MWD)]changes were compared between the two groups before and after treatment to evaluate the clinical efficacy.The adverse effects of drugs were also counted.Results After 14 days of treatment,the total effective rate in the observation group was higher than that in the control group(P=0.012).Hemodynamics(PASP,mPAP,TRV,RVOT,Tei index,LVEF),blood gas analysis(PaO2,PaCO2)and vasoactive factor(ET-1,NO,VEGF)of the two groups were significantly improved compared with those before treatment(all P<0.01),but the improvement of the observation group was more significant(P<0.05).There was no significant difference in the incidence of adverse drug reactions between the two groups(χ^2=0.809,P=0.368).Conclusion Fasudil combined with sildenafil can safely and effectively reduce pulmonary artery pressure in patients with COPDPAH.The mechanism may be related to the decrease of serum ET-1,VEGF level and the increase of serum NO level.