McClure David L, Valuck Robert J, Glanz Morton, Hokanson John E
Kaiser Foundation Health Plan of Colorado, Clinical Research Unit, Denver, CO 80237-8066, USA.
Pharmacoepidemiol Drug Saf. 2007 Feb;16(2):132-43. doi: 10.1002/pds.1341.
Our objective was to determine the association of clinically relevant adverse events from a systematic review and meta-analysis of statin randomized controlled trials (RCT).
We performed the meta-analysis in the manner of a Cochrane Collaboration systematic review. Outcomes were discontinuances of therapy or muscle-related symptoms due to adverse events. We searched for articles from 1982 through June 2006 in MEDLINE and other databases. The main inclusion criteria were double blind, placebo controlled RCTs with a monotherapy intervention of any marketed statin and active surveillance of adverse events. We excluded studies of drug interactions, organ transplants, or exercise, or those not meeting all of the study quality criteria. The primary analysis was a statin formulation stratified fixed-effect model using Peto odds-ratios (POR). Secondary analyses explored the stability of the primary results.
Over 86,000 study participants from 119 studies were included. Available statins were associated with a lower POR of discontinuance (overall: 0.88 [0.84, 0.93], largest effect with pravastatin: 0.79 [0.74, 0.84]), an elevated POR of rhabdomyolysis (1.59 [0.54, 4.70]) and myositis (2.56 [1.12, 5.85]), and null odds of myalgia (1.09 [0.97, 1.23]). Cerivastatin by comparison demonstrated larger PORs for discontinuances and muscle-related adverse events. Secondary analyses demonstrated the stability of the results.
Overall, discontinuation of statin therapy due to adverse events was no worse than placebo. The risks of muscle-related adverse events were in general agreement with the known risks of statins.
我们的目标是通过对他汀类随机对照试验（RCT）的系统评价和荟萃分析来确定临床相关不良事件之间的关联。
我们按照Cochrane协作网系统评价的方式进行荟萃分析。结局指标为因不良事件导致的治疗中断或肌肉相关症状。我们在MEDLINE及其他数据库中检索了1982年至2006年6月的文章。主要纳入标准为双盲、安慰剂对照的RCT，采用任何市售他汀类药物进行单药治疗干预，并对不良事件进行主动监测。我们排除了药物相互作用、器官移植或运动相关的研究，以及那些不符合所有研究质量标准的研究。主要分析是使用Peto比值比（POR）的他汀类药物剂型分层固定效应模型。次要分析探讨了主要结果的稳定性。
纳入了来自119项研究的超过86,000名研究参与者。现有他汀类药物与较低的治疗中断POR相关（总体：0.88 [0.84, 0.93]，普伐他汀的效应最大：0.79 [0.74, 0.84]），横纹肌溶解的POR升高（1.59 [0.54, 4.70]）和肌炎的POR升高（2.56 [1.12, 5.85]），而肌痛的比值比为零（1.09 [0.97, 1.23]）。相比之下，西立伐他汀在治疗中断和肌肉相关不良事件方面显示出更大的POR。次要分析证明了结果的稳定性。
总体而言，因不良事件停用他汀类药物治疗并不比安慰剂更差。肌肉相关不良事件的风险与他汀类药物已知风险总体一致。
