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他汀类药物都一样吗?普伐他汀、辛伐他汀和阿托伐他汀预防心血管疾病的随机试验证据。

Are statins created equal? Evidence from randomized trials of pravastatin, simvastatin, and atorvastatin for cardiovascular disease prevention.

作者信息

Zhou Zheng, Rahme Elham, Pilote Louise

机构信息

Department of Epidemiology and Biostatistics, McGill University, Montréal, Quebec, Canada.

出版信息

Am Heart J. 2006 Feb;151(2):273-81. doi: 10.1016/j.ahj.2005.04.003.

Abstract

BACKGROUND

The relative efficacy of different statins for long-term cardiovascular prevention remains largely undetermined.

METHODS

Using adjusted indirect comparison, we compared 3 statins (pravastatin, simvastatin, and atorvastatin) based on published randomized placebo-controlled trials for long-term cardiovascular prevention. A systematic literature search between 1980 and 2004 was conducted. Randomized placebo-controlled trials of the 3 statins, which studied cardiovascular diseases or death as the outcome, enrolled > or = 1000 participants, and had > or = 1-year follow-up, were included. Trials were grouped according to the statin under study. A pooled relative risk (RR) was derived from each set of trials using a random-effects model. Adjusted indirect comparisons using pooled RRs were made between statins with regard to prespecified clinical outcomes.

RESULTS

Eight placebo-controlled trials met the inclusion criteria, including 4 pravastatin trials (n = 25,572), 2 simvastatin trials (n = 24,980), and 2 atorvastatin trials (n = 13,143). All trials had a similar degree of lipid reduction. Graphical and statistical assessments showed minimal heterogeneity in the trials' effect sizes. Adjusted indirect comparisons did not reveal a statistically significant difference between statins in reducing fatal coronary heart disease and nonfatal myocardial infarctions (simvastatin vs pravastatin: RR 0.93 [95% CI 0.84-1.03]; atorvastatin vs simvastatin: RR 0.84 [95% CI 0.66-1.08]; atorvastatin vs pravastatin: RR 0.79 [95% CI 0.61-1.02]). We were unable to detect differences either in outcomes for fatal and nonfatal strokes, all cardiovascular deaths, and all-cause mortality.

CONCLUSION

Evidence from published statin randomized placebo-controlled trials suggests that pravastatin, simvastatin, and atorvastatin, when used at their standard dosages, show no statistically significant difference in their effect on long-term cardiovascular prevention.

摘要

背景

不同他汀类药物用于长期心血管疾病预防的相对疗效在很大程度上仍未确定。

方法

采用校正间接比较法,基于已发表的随机安慰剂对照试验,对3种他汀类药物(普伐他汀、辛伐他汀和阿托伐他汀)进行长期心血管疾病预防效果的比较。我们在1980年至2004年间进行了系统的文献检索。纳入了以心血管疾病或死亡为结局、研究对象≥1000例且随访时间≥1年的3种他汀类药物的随机安慰剂对照试验。试验根据所研究的他汀类药物进行分组。使用随机效应模型从每组试验中得出合并相对危险度(RR)。针对预先设定的临床结局,使用合并RR进行他汀类药物之间的校正间接比较。

结果

8项安慰剂对照试验符合纳入标准,其中包括4项普伐他汀试验(n = 25572)、2项辛伐他汀试验(n = 24980)和2项阿托伐他汀试验(n = 13143)。所有试验的降脂程度相似。图形和统计学评估显示,试验效应大小的异质性极小。校正间接比较未显示他汀类药物在降低致命性冠心病和非致命性心肌梗死方面存在统计学显著差异(辛伐他汀对比普伐他汀:RR 0.93 [95% CI 0.84 - 1.03];阿托伐他汀对比辛伐他汀:RR 0.84 [95% CI 0.66 - 1.08];阿托伐他汀对比普伐他汀:RR 0.79 [95% CI 0.61 - 1.02])。我们也未能检测到在致命性和非致命性卒中、所有心血管死亡以及全因死亡率的结局方面存在差异。

结论

已发表的他汀类药物随机安慰剂对照试验证据表明,普伐他汀、辛伐他汀和阿托伐他汀在使用标准剂量时,对长期心血管疾病预防的效果无统计学显著差异。

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