不同剂型曲前列环素治疗肺动脉高压的临床疗效及安全性

The efficacy and safety of treprostinil with different administrations in pulmonary arterial hypertension

目的:系统评价不同剂型曲前列环素治疗肺动脉高压的临床疗效及安全性。方法:由两名研究者独自在英文数据库(PubMed、Cochrane Library、EMBASE)及中文数据库(万方、中国生物医学文献数据库、维普及中国知网)检索,检索时间至2018年6月。根据纳入及排除标准由两名研究者独立选择文献、提取数据及评价文献质量,采用Stata 14.1软件对效应值分别进行Meta分析。结果:最终共纳入11项研究,共纳入曲前列环素治疗肺动脉高压患者933例,其中42.0%为皮下注射型,5.0%为静脉注射型,33.4%为口服型及19.6%为吸入型。研究结果显示曲前列环素治疗肺动脉高压的病死率仅为2.5%,以静脉注射型治疗较常见。Meta分析结果显示曲前列环素可明显提高6MWD,SMD皮下=4.34(95%CI[1.46,7.30],P=0.003)、SMD静脉=3.27(95%CI[0.01,6.53],P=0.049)、SMD吸入=0.33(95%CI[0.12,0.53],P=0.002)及SMD口服=0.30(95%CI[0.05,0.54],P=0.017);其中皮下注射型可降低Borg呼吸困难评分(SMD=-2.87,95%CI[-4.44,1.30],P<0.001);而静脉注射型不仅可有效降低患者的Borg评分(SMD=-3.27(95%CI[-4.48,-2.48],P<0.001),同时提高心脏指数(SMD=5.24,95%CI[4.08,6.41],P<0.001),降低患者平均肺动脉压力(SMD=-1.65,95%CI[-2.58,-0.72],P<0.001)及肺循环阻力(SMD=-4.66,95%CI[-7.53,-1.79],P=0.001)。口服型及吸入型曲前列环素相关研究显示其并不能有效改善患者心功能、呼吸功能及临床恶化率。结论:曲前列环素为肺动脉高压的安全性药物,而不同剂型的临床疗效存在一定差异,其中皮下注射型及静脉注射型可明显改善患者的运动耐量及呼吸功能,且后者对肺血管有明显改善作用;但口服型及吸入型曲前列环素的有效性有待进一步研究。

Objective:A systematic review and meta-analysis was conducted to study the efficacy and safety of treprostinil with different administrations for patients with pulmonary arterial hypertension.Method:English databases(PubMed,Cochrane Library and EMBASE)and Chinese databases(WanFang Data,CBM,VIP and CNKI)were searched up to June.2018.The two reviewers independently screened the studies,extracted data and conducted the quality assessment,and the meta-analysis was performed by Stata 14.1.Result:Eleven studies meeting the inclusion criteria were pooled in this study that involved 933 PAH patients with treprostinil,with 42.0%subcutaneous,5.0%intravenous,33.4% oral and 19.6% inhaled.It is demonstrated a rough mortality of 2.5% with treprostinil treatment,and a higher rate with intravenous administration.It is showed an amelioration of 6 MWD with a statistical significance,SMDsub=4.34(95%CI[1.46,7.30],P=0.003),SMDint=3.27(95%CI[0.01,6.53],P=0.049),SMDinh=0.33(95%CI[0.12,0.53],P=0.002)and SMDora=0.30(95%CI[0.05,0.54],P=0.017).Meanwhile,the subcutaneous treprostinil could reduce Borg dyspnea score(SMD=-2.87,95%CI[-4.44,1.30],P<0.001).While the intravenous could not only decrease Borg dyspnea score(SMD=-3.27(95%CI[-4.48,-2.48],P<0.001),but also improve cardiac index(SMD=5.24,95%CI[4.08,6.41],P<0.001),lower mean pulmonary arterial hypertension(SMD=-1.65,95%CI[-2.58,-0.72],P<0.001)and pulmonary vascular resistance(SMD=-4.66,95%CI[-7.53,-1.79],P=0.001).Nevertheless,the studies about oral treprostinil and aerosolized treprostinil have demonstrated no significant changes in functional class,Borg dyspnea score,clinical worsening and symptoms of PAH.Conclusion:Treprostinil is a safe drug for PAH,and it showed subcutaneous and intravenous administrations could improve the exercise tolerance and Borg score,in addition to the pulmonary vessels.Still,a further research should be suggested for an efficacy of inhaled and oral treprostinil.