Department of Preventive Medicine and Population Health, University of Texas Medical Branch at Galveston, Galveston, Texas, USA.
Department of Preventive Medicine and Population Health, University of Texas Medical Branch at Galveston, Galveston, Texas, USA
BMJ Open. 2021 Jun 15;11(6):e043714. doi: 10.1136/bmjopen-2020-043714.
OBJECTIVE: To estimate relative risk (RR) of statin-associated musculoskeletal symptoms by statin therapy intensity. SETTING: Network meta-analysis assessing multicentre randomised controlled trials (RCTs) across several countries. PARTICIPANTS: PubMed, Web of Science, Cochrane database and ClinicalTrials.gov were searched through January 2021 for doubled-blinded RCTs testing the effect of statin therapy on lipids with at least 1000 participants and 2 years of intended treatment. Two coders assessed articles for final inclusion, quality and outcomes. Treatment intensity was categorised according to American Heart Association definitions. OUTCOMES: Pairwise and network meta-analysis (NMA) estimated RR and risk difference with random effects modelling. Heterogeneity was evaluated with the I statistic. Outcomes included muscle symptoms (any, myalgia and attrition due to muscle symptoms), rhabdomyolysis and elevated creatine kinase (CK) (>10 × upper limit of normal). RESULTS: Of 2919 RCTs, 24 (n=152 461) met inclusion criteria. NMA results indicated risk was significantly greater for high compared with moderate intensity statin therapy for any muscle problem (RR=1.04, 95% CI 1.00 to 1.07; I=0%), myalgia (RR=1.04, 95% CI 1.00 to 1.08; I=0%, number needed to harm (NNH)=173), attrition due to muscle problems (RR=1.37, 95% CI 1.09 to 1.73, I=0%, NNH=218) and elevated CK (RR=4.69, 95% CI 2.50 to 8.80; I=7%, NNH=527). Risk also was significantly higher for high intensity compared with placebo for any muscle problem (RR=1.05, 95% CI 1.01 to 1.09, I=0%), myalgia (RR=1.13, 95% CI 1.05 to 1.23; I=0%, NNH=182), attrition due to muscle problems (RR=1.55, 95% CI 1.15 to 2.08, I=0%, NNH=187) and elevated CK (RR=5.37, 95% CI 2.48 to 11.61; I=7%, NNH=589). Due to inconsistency of results across sensitivity analyses, estimates were inconclusive for rhabdomyolysis and CK. There were no significant differences in risk between moderate intensity therapy and placebo for all outcomes. CONCLUSIONS: For approximately each 200 patients on high intensity statins, one additional patient may experience myalgia or discontinue therapy due to muscle problems compared with moderate intensity therapy. TRIAL REGISTRATION NUMBER: CRD42019112758.
目的：通过他汀类药物治疗强度评估他汀类药物相关肌肉骨骼症状的相对风险（RR）。
设定：评估多国多中心随机对照试验（RCT）的网络荟萃分析。
参与者：通过PubMed、Web of Science、Cochrane 数据库和 ClinicalTrials.gov 检索了截至 2021 年 1 月的测试他汀类药物治疗对血脂影响的双盲 RCT，至少有 1000 名参与者和 2 年的预期治疗。两名编码员评估了最终纳入、质量和结局的文章。根据美国心脏协会的定义对治疗强度进行分类。
结局：通过随机效应模型进行了两两和网络荟萃分析（NMA）以估计 RR 和风险差异。使用 I 统计量评估了异质性。结局包括肌肉症状（任何、肌痛和因肌肉症状而退出）、横纹肌溶解症和肌酸激酶（CK）升高（>10×正常上限）。
结果：在 2919 项 RCT 中，有 24 项（n=152461 名）符合纳入标准。NMA 结果表明，高强度他汀类药物治疗与中强度他汀类药物治疗相比，任何肌肉问题（RR=1.04，95%CI 1.00 至 1.07；I=0%）、肌痛（RR=1.04，95%CI 1.00 至 1.08；I=0%，危害比（NNT）=173）、因肌肉问题而退出（RR=1.37，95%CI 1.09 至 1.73，I=0%，NNT=218）和 CK 升高（RR=4.69，95%CI 2.50 至 8.80；I=7%，NNT=527）的风险显著更高。高强度他汀类药物治疗与安慰剂相比，任何肌肉问题（RR=1.05，95%CI 1.01 至 1.09，I=0%）、肌痛（RR=1.13，95%CI 1.05 至 1.23；I=0%，NNT=182）、因肌肉问题而退出（RR=1.55，95%CI 1.15 至 2.08，I=0%，NNT=187）和 CK 升高（RR=5.37，95%CI 2.48 至 11.61；I=7%，NNT=589）的风险也显著更高。由于敏感性分析结果不一致，横纹肌溶解症和 CK 的估计结果不确定。中强度治疗与安慰剂相比，所有结局的风险均无显著差异。
结论：与中强度他汀类药物治疗相比，大约每 200 名接受高强度他汀类药物治疗的患者中，就会有 1 名患者可能会出现肌痛或因肌肉问题而停止治疗。
试验注册：CRD42019112758。
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