口服西地那非治疗肺动脉高压的效果和安全性初步研究

目的 国外研究表明西地那非能有效地降低肺动脉高压,改善活动耐量,提高生活质量.但中国肺动脉高压患者服用西地那非的效果和安全性尚不清楚.本研究旨在明确中国肺动脉高压患者口服西地那非的临床效果及安全性.方法 采用前瞻性、开放、多中心临床研究方法,根据右心导管检查结果进行病例筛选.所有人选患者口服枸橼酸西地那非25 mg,3次/d,共12周.观察基线和12周后所有患者6 min步行距离和血流动力学指标的变化.主要终点是6 min步行距离的变化.次要终点包括:Borg呼吸困难积分、世界卫生组织(WHO)肺动脉高压功能分级的改善、血流动力学指标的变化以及临床恶化(指死亡、心肺移植、再住院等)的情况.还观察了药物的安全性和耐受性.结果 共入选14个中心的90例肺动脉高压患者,其中男性19例,女性71例;年龄18～61岁,平均32.5岁.特发性肺动脉高压患者15例,先天性心脏病相关性肺动脉高压患者60例,结缔组织病相关性肺动脉高压患者9例,慢性血栓栓塞性肺动脉高压患者6例.患者口服西地那非12周后,6min步行距离明显提高,由基线(342±93)m增加到(403±88)m,P＜0.001;Borg呼吸困难积分由基线2.9±2.6降至2.4±2.0,P=0.005;肺动脉平均压由(73±21)mm Hg(1 mm Hg=0.133 kPa)降至(67±19)mm Hg,P=0.001;心指数由(2.6±1.3)L·min-1·m-2增加至(3.2±1.5)L·min-1·m-2,P＜0.001;肺血管阻力由(1744±908)dyn·s·cm-5降至(1334±657)dyn·s·cm-5,P＜0.001;而且世界卫生组织(WHO)肺动脉高压功能分级明显改善;口服西地那非副作用轻微.结论 本研究表明中国肺动脉高压患者口服西地那非可以提高患者的运动耐量、降低肺动脉压、提高生存质量,并有良好的耐受性.

Abstract：

Objective Sildenafil has been shown to be effective in pulmonary arterial hypertension (PAH).However,the impact of sildenafil on PAH has been under-investigated in China.The aim of the present study was to evaluate the efficacy and safety of oral sildenafil in PAH patients in China.Methods In this prospective,open-label and multi-center study,90 patients were recruited from 14 centers to receive oral sildenafil (75 mg/d) for 12 weeks.They underwent a six-minute walk test (SMWT) and cardiac catheterization at the beginning and the end of 12 weeks.The primary endpoint was the changes in exercise capacity as assessed by SMWT.And the secondary endpoints included assessment of functional class,evaluation of cardiopulmonary hemodynamics and clinical deterioration (defined as death,transplantation and re-hospitalization for PAH).Drug safety and tolerability were also examined.Results There were 19 males and 71 females with an average age of 32.5±12.1 years old(range: 18-61 ).Their etiologies were idiopathic (n=15),related with congenital heart disease ( n = 60 ),or related with connective tissue disease (n=9) and chronic thromboembombolic pulmonary hypertension ( n = 6).Oral sildenafil significantly increased the SMWT distances [(342±93) m vs.(403±88) m,P＜0.001].There was also remarkable improvement in Borg dyspnea score ( 2.9 ± 2.6 vs.2.4 ± 2.0,P = 0.005 ).Furthermore,significant improvements in World Healthy Organization (WHO) functional class and cardiopulmonary hemodynamics were also found ( mean pulmonary artery pressure,P ＜ 0.001; cardiac index,P ＜ 0.001; pulmonary vascular resistance,P ＜ 0.001 ).Side effects were mild and consistent with other reports.Conclusion This study confirms and extends previous studies.Oral sildenafil is both safe and effective for the treatment of adult PAH patients in China.

Preliminary study on the efficacy and safety of oral sildenafil in pulmonary arterial hypertension in China

Objective Sildenafil has been shown to be effective in pulmonary arterial hypertension (PAH).However,the impact of sildenafil on PAH has been under-investigated in China.The aim of the present study was to evaluate the efficacy and safety of oral sildenafil in PAH patients in China.Methods In this prospective,open-label and multi-center study,90 patients were recruited from 14 centers to receive oral sildenafil (75 mg/d) for 12 weeks.They underwent a six-minute walk test (SMWT) and cardiac catheterization at the beginning and the end of 12 weeks.The primary endpoint was the changes in exercise capacity as assessed by SMWT.And the secondary endpoints included assessment of functional class,evaluation of cardiopulmonary hemodynamics and clinical deterioration (defined as death,transplantation and re-hospitalization for PAH).Drug safety and tolerability were also examined.Results There were 19 males and 71 females with an average age of 32.5±12.1 years old(range: 18-61 ).Their etiologies were idiopathic (n=15),related with congenital heart disease ( n = 60 ),or related with connective tissue disease (n=9) and chronic thromboembombolic pulmonary hypertension ( n = 6).Oral sildenafil significantly increased the SMWT distances [(342±93) m vs.(403±88) m,P＜0.001].There was also remarkable improvement in Borg dyspnea score ( 2.9 ± 2.6 vs.2.4 ± 2.0,P = 0.005 ).Furthermore,significant improvements in World Healthy Organization (WHO) functional class and cardiopulmonary hemodynamics were also found ( mean pulmonary artery pressure,P ＜ 0.001; cardiac index,P ＜ 0.001; pulmonary vascular resistance,P ＜ 0.001 ).Side effects were mild and consistent with other reports.Conclusion This study confirms and extends previous studies.Oral sildenafil is both safe and effective for the treatment of adult PAH patients in China.