Lancet. 2022 Sep 10;400(10355):832-845. doi: 10.1016/S0140-6736(22)01545-8. Epub 2022 Aug 29.
Statin therapy is effective for the prevention of atherosclerotic cardiovascular disease and is widely prescribed, but there are persisting concerns that statin therapy might frequently cause muscle pain or weakness. We aimed to address these through an individual participant data meta-analysis of all recorded adverse muscle events in large, long-term, randomised, double-blind trials of statin therapy.
Randomised trials of statin therapy were eligible if they aimed to recruit at least 1000 participants with a scheduled treatment duration of at least 2 years, and involved a double-blind comparison of statin versus placebo or of a more intensive versus a less intensive statin regimen. We analysed individual participant data from 19 double-blind trials of statin versus placebo (n=123 940) and four double-blind trials of a more intensive versus a less intensive statin regimen (n=30 724). Standard inverse-variance-weighted meta-analyses of the effects on muscle outcomes were conducted according to a prespecified protocol.
Among 19 placebo-controlled trials (mean age 63 years [SD 8], with 34 533 [27·9%] women, 59 610 [48·1%] participants with previous vascular disease, and 22 925 [18·5%] participants with diabetes), during a weighted average median follow-up of 4·3 years, 16 835 (27·1%) allocated statin versus 16 446 (26·6%) allocated placebo reported muscle pain or weakness (rate ratio [RR] 1·03; 95% CI 1·01-1·06). During year 1, statin therapy produced a 7% relative increase in muscle pain or weakness (1·07; 1·04-1·10), corresponding to an absolute excess rate of 11 (6-16) events per 1000 person-years, which indicates that only one in 15 ([1·07-1·00]/1·07) of these muscle-related reports by participants allocated to statin therapy were actually due to the statin. After year 1, there was no significant excess in first reports of muscle pain or weakness (0·99; 0·96-1·02). For all years combined, more intensive statin regimens (ie, 40-80 mg atorvastatin or 20-40 mg rosuvastatin once per day) yielded a higher RR than less intensive or moderate-intensity regimens (1·08 [1·04-1·13] vs 1·03 [1·00-1·05]) compared with placebo, and a small excess was present (1·05 [0·99-1·12]) for more intensive regimens after year 1. There was no clear evidence that the RR differed for different statins, or in different clinical circumstances. Statin therapy yielded a small, clinically insignificant increase in median creatine kinase values of approximately 0·02 times the upper limit of normal.
Statin therapy caused a small excess of mostly mild muscle pain. Most (>90%) of all reports of muscle symptoms by participants allocated statin therapy were not due to the statin. The small risks of muscle symptoms are much lower than the known cardiovascular benefits. There is a need to review the clinical management of muscle symptoms in patients taking a statin.
British Heart Foundation, Medical Research Council, Australian National Health and Medical Research Council.
他汀类药物治疗对预防动脉粥样硬化性心血管疾病非常有效，应用广泛，但人们一直担心他汀类药物治疗可能会经常引起肌肉疼痛或无力。我们旨在通过对他汀类药物治疗的大型、长期、随机、双盲试验中所有记录的不良肌肉事件的个体参与者数据进行荟萃分析来解决这些问题。
如果他汀类药物治疗试验旨在招募至少 1000 名计划治疗时间至少 2 年的参与者，并且涉及他汀类药物与安慰剂或更强化与较不强化他汀类药物方案的双盲比较，则符合入选条件。我们对 19 项他汀类药物与安慰剂的双盲试验（n=123940）和 4 项更强化与较不强化他汀类药物方案的双盲试验（n=30724）的个体参与者数据进行了分析。根据预先规定的方案，对肌肉结局的影响进行了标准逆方差加权荟萃分析。
在 19 项安慰剂对照试验中（平均年龄 63 岁[标准差 8]，其中 34533 名[27.9%]女性，59610 名[48.1%]有既往血管疾病，22925 名[18.5%]有糖尿病），在平均中位随访 4.3 年期间，16835 名（27.1%）分配他汀类药物与 16446 名（26.6%）分配安慰剂报告肌肉疼痛或无力（率比[RR]1.03；95%置信区间 1.01-1.06）。在第 1 年，他汀类药物治疗使肌肉疼痛或无力的相对发生率增加了 7%（1.07；1.04-1.10），对应的绝对超额发生率为每 1000 人年 11 例（6-16），这表明只有 15 分之一（[1.07-1.00]/1.07）的这些与肌肉相关的报告实际上是由他汀类药物引起的。第 1 年后，首次报告肌肉疼痛或无力没有明显的过量（0.99；0.96-1.02）。所有年份合并后，与安慰剂相比，强化他汀类药物方案（即每天 40-80 mg 阿托伐他汀或 20-40 mg 瑞舒伐他汀）的 RR 更高（1.08[1.04-1.13]与 1.03[1.00-1.05]），且强化方案在第 1 年后有少量的超额（1.05[0.99-1.12]）。没有明确证据表明不同的他汀类药物或不同的临床情况下 RR 存在差异。他汀类药物治疗使肌酸激酶中位数升高约 0.02 倍，接近正常值上限，这是一个较小的、临床上无显著意义的增加。
他汀类药物治疗导致了大多数为轻度的肌肉疼痛的轻微过度发生。大多数（>90%）参与者报告的肌肉症状不是由他汀类药物引起的。肌肉症状的小风险远低于已知的心血管益处。需要重新评估服用他汀类药物的患者的肌肉症状的临床管理。
以上是对原文的逐句翻译，可能存在不符合中文表达习惯的问题。
