肺动脉高压联合治疗的荟萃分析

目的 对现已完成的肺动脉高压联合治疗的随机对照试验进行荟萃分析,评价肺动脉高压联合治疗的有效性和安全性.方法 检索Cochrane图书馆、MEDLINE、EMBASE、PubMed、Elsevier数据库、中国生物医学文献数据库和ClinicalTrials.gov等中2001～2012年已完成的有关肺动脉高压联合治疗的随机对照试验,按纳入排除标准收集相关资料.按Cochrane系统评价方法,由2名评价者独立评价所纳入研究的文献质量,提取有效数据后,采用RevMan 5.1软件进行荟萃分析.结果 纳入9个随机对照研究,包括979例肺动脉高压患者.荟萃分析结果显示:与单药治疗组相比,联合用药组能改善患者6分钟步行距离,加权标准差(WMD)=24.37 m,95％CI=11.24～37.50(P＜0.01)、降低临床恶化率(RR =0.50,95％ CI =0.31～0.83,P＜0.01),但不能降低患者病死率(RR=0.55,95％CI=0.21～1.44,P＞0.05).联合用药组与单药治疗组间药物相关的严重不良事件率和研究中断率(RR=0.86,95％ CI =0.52～1.44,P＞0.05)差异无统计学意义.结论 与单药治疗相比,联合用药可提高肺动脉高压患者运动耐量,减少临床恶化,而且联合用药是安全的、易耐受的；但对患者病死率无影响.尚需更多大型的随机对照试验来进一步评价联合治疗的有效性和安全性.

Combination therapy in pulmonary arterial hypertension:a meta-analysis

Objective To perform a meta-analysis of all finished randomized controlled trials （RCTs） for assessing the efficacy and safety of combination therapy in patients with pulmonary arterial hypertension. Methods We searched the Coehrane Library, the MEDLINE, EMBASE, PubMed, Elsevier, CBM databases and ClinicalTrials. gov from 2001 to 2012 to identify all RCTs comparing the efficacy and safety of combination therapy to those of monotherapy in patients with pulmonary arterial hypertension. According to the Cochrane Handbook for systematic reviews ,quality assessment and data extraction were conducted by two reviewers independently. All data were analyzed by using Review Manager 5.1. Results Nine trials with a total of 979 patients were included in our meta-analysis. The results of meta-analysis showed that , compared to monotherapy, combination therapy significantly increased the 6-min walk distance at the end of follow-up, weighted mean difference（WMD） 24.37 m,9516 confidence interval（ CI = 11.24- 37.50, P 〈0.01）,and reduced clinical worsening risk ratio（ RR =0.50,95% CI =0.31-0.83, P d0.01）, but it could not reduce mortality （ RR = 0.55,95 % CI = 0.21-1.44, P〉0.05）. The incidence of drug-related serious adverse events and study-drug discontinuation were similar in two groups （ RR = 0.86,95 % CI = 0.52- 1.44, P 0.05）. Conclusion In patients with pulmonary arterial hypertension,compared with monotherapy,combination therapy significantly increases exercise capacity and reduces clinical worsening. Moreover, it is safe and well tolerated. However, it has no effect on mortality. More large-scale RCTs are warranted to further assess the efficacy and safety of combination therapy in this setting.