他汀类药物治疗肺高血压的Meta分析

A Meta-analysis of statins therapy for pulmonary hypertension

目的系统评价他汀类药物治疗肺高血压的有效性和安全性。方法系统检索PubMed、中国知识基础设施工程(CNKI)、Web of science和the Cochrane central register of controlled trials database等数据库,全面收集他汀类药物治疗肺高血压患者的前瞻性、随机、对照临床试验(RCT)。按纳入排除标准筛选文献、提取资料和进行方法学质量评价。应用RevMan 5.04软件进行Meta分析,采用标准化均数差(SMD)和相对危险度(RR)在随机或固定效应模式下合并统计量。主要分析他汀类药物治疗肺高血压患者前后运动耐量(6min步行距离或Naughton步行时间)的变化。同时评价他汀类药物治疗前后肺动脉压力的变化,以及药物不良反应和临床恶化事件发生率。并按照肺高血压临床分类进行亚组分析。结果共纳入7个RCT(包括4个安慰剂对照试验和3个非安慰剂对照试验),684例肺高血压患者符合纳入标准。与对照组相比,他汀类药物能改善肺高血压患者的运动耐量(SMD=0.47,95%CI为0.08~0.87,P=0.02),尤其在第3类肺高血压(即呼吸系统疾病相关性肺高血压)患者中的作用明显(SMD=0.84,95%CI为0.36~1.33,P=0.000 6)。他汀类药物可降低肺高血压患者肺动脉压力(SMD=-0.53,95%CI为-0.95^-0.11,P=0.01)。两组间药物相关不良反应(RR=1.08,95%CI为0.55~2.09)、临床恶化事件发生率(RR=0.84,95%CI为0.55~1.30)的差异均无统计学意义(P值均>0.05)。结论他汀类药物可显著改善肺高血压患者的运动耐量,降低肺动脉压力。未来仍需更多大型RCT证实他汀类药物治疗肺高血压患者的临床疗效和安全性。

Objective To evaluate the safety and efficacy of statins therapy in patients with pulmonary hypertension （PH）. Methods Literatures published were searched in the database including PubMed, China national knowledge infrastructure, （CNKI）, Web of Science and the Ccohrane Central Register of Controlled Trials to collect prospective randomized control trials （ROT） of statin treatment for PH. The studies were evaluated and screened strictly according to the inclusion and exclusion criteria. Meta-analysis was conducted by RevMan 5.04 software to evaluate the changes in exercise capacity （as indicated by six-minute walking distance or Naughton walking time） and pulmonary arterial pressure, drug adverse reaction and clinical worsening events. Standardized mean difference （SMD）, risk ratio （RR） and 95 % confidence interval （OI） were calculated by using random-effect or fixed-effect model. Subgroup analysis was conducted based on the clinical classification of PH. Results Seven ROTs （4 placebo-controlled and 3 non-placebo- controlled trials） were enrolled and a total of 684 patients with PH met the inclusion criteria. The meta-analysis demonstrated that compared with control group, exercise capacity in statin group was significantly improved （SMD=0.47, 95% OI [0.08- 0. 871, P = 0.02）, mainly in patients with PH associated with diseases of respiratory system （SMD= 0.84, 95% CI [0.36 - 1. 33], P = 0. 000 6）. The pulmonary arterial pressure （PAP） was significantly decreased after statin treatment （SMD = - 0.53, 95 % CI[0.95 - 0.11], P = 0.01 ）. The incidences of drug adverse reaction （RR= 1.08, 95%CI [0.55-2.09], P=0.68） and clinical worsening events （RR=0.84, 95%OI [0.55- 1.30], P = 0.44） in statin group were not significantly different from control group （all P〉0.05）. Conclusion Statin therapy has beneficial effects on PH, such as improving exercise capacity and decreasing pulmonary arterial pressure. Clearly, more large-sample ROTs are warranted to identify the role of statin therapy in PH. （Shanghai Meal J, 2014, 37.. 581-586）