中国患者应用大剂量阿托伐他汀安全性的Meta分析

Safety of high-dose atorvastatin in Chinese patients: a Meta-analysis

目的系统评价中国患者应用大剂量阿托伐他汀（80 mg/d）的安全性。方法计算机检索EMbase、Pub Med、The Cochrane Library、万方、CNKI、维普数据库,收集80 mg/d阿托伐他汀与小剂量阿托伐他汀或安慰剂或空白对照比较的随机对照试验（RCT）,采用Rev Man 5.2及Stata 11.0软件进行Meta分析。结果共纳入了18项RCT。80 mg/d阿托伐他汀组的胃肠道不良反应（RR 1.53,95%CI 0.85~2.76,P=0.16）、肝不良反应（RR 1.53,95%CI 0.99~2.36,P=0.05）、肌肉不良反应（RR 1.51,95%CI 0.92~2.49,P=0.10）、严重肝不良反应（RR 2.33,95%CI 0.88~6.20,P=0.09）和严重肌肉不良反应（RR 1.40,95%CI 0.46~4.30,P=0.56）发生率与对照组比较,差异均无统计学意义。根据80 mg/d阿托伐他汀服药时长、对照不同进行亚组分析显示,空白对照亚组胃肠道不良反应（RR 4.22,95%CI 1.11~16.04,P=0.03）发生率的差异有统计学意义。结论目前的证据表明,80 mg/d阿托伐他汀可能不会使胃肠道、肝、肌肉不良反应发生风险升高,不会导致严重肝及肌肉损害。但因受纳入研究的质量和数量等限制,尚需更多高质量的RCT来验证。

Objective To systematically evaluate the safety of high dose atorvastatin（ 80 mg daily）in Chinese patients. Methods Randomized controlled trials（ RCTs） investigating 80 mg / d atorvastatin vs.low-dose atorvastatin or placebo or blank were electionically retrieved in date bases of EMbase,Pub Med,the Cochrane Library,Wan Fang,CNKI and Wei Pu. Meta-analysis was performed using Rev Man 5. 2 and Stata11. 0 software. Results A total of 20 RCTs involving 2282 cases were included. The results of metaanalysis showed no significant differences betweent the 80 mg / d atorvastatin group and the control group in the incidence of gastrointestinal adverse events（ RR 1. 53,95% CI 0. 85-2. 76,P = 0. 16）,hepatic adverse events（ RR 1. 53,95% CI 0. 99- 2. 36,P = 0. 05）,muscular adverse events（ RR 1. 51,95% CI 0. 92-2. 49,P = 0. 10）,serious hepatic injuries（ RR 2. 33,95% CI 0. 88- 6. 20,P = 0. 09） and serious muscular myopathies（ RR 1. 40,95% CI 0. 46- 4. 30,P = 0. 56）. Subgroup analysis by type of cotrast media used and durations of taking 80 mg / d atorvastatin showed there were higher risks of gastrointestinal adverse events in the 80 mg / d group when compared to blank control（ RR 4. 22,95% CI 1. 11- 16. 04,P = 0. 03）. Conclusions The current evidence shows that 80 mg / d atorvastatin may be relatively safe in terms of adverse events in gastrointestinal tract,liver and muscular system,and relatively has risk in causing severe liver injuries and myopathies. With limited quantity and quality from the RCTs available,more high quality RCTs are needed to verify the above conclusion.