Intensity of statin therapy and muscle symptoms: a network meta-analysis of 153,000 patients

Objective: To estimate relative risk of statin-associated musculoskeletal symptoms (SAMS) by statin therapy intensity. Setting: Network meta-analysis assessing multi-center 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 two years of intended treatment. Two coders assessed articles for final inclusion, quality, and outcomes. Treatment intensity was categorized according to American Heart Association definitions. Outcomes: Pairwise and network meta-analysis (NMA) estimated relative risk (RR) and risk difference (RD) with random effects modeling. Heterogeneity was evaluated with the I2 statistic. Outcomes included muscle symptoms (any, myalgia, and attrition due to muscle symptoms), rhabdomyolysis, and elevated creatine kinase (>10x upper limit of normal). Results: Of 2801 RCTs...研究目的：基于他汀类药物治疗强度，评估他汀相关肌肉骨骼症状（statin-associated musculoskeletal symptoms, SAMS）的相对风险。 研究场景：本研究为一项针对多国多中心随机对照试验（randomized controlled trial, RCT）的网络Meta分析。 研究对象与文献筛选：截至2021年1月，在PubMed、Web of Science、Cochrane数据库以及ClinicalTrials.gov中检索符合以下条件的双盲随机对照试验：评估他汀类药物对血脂的干预效果，试验纳入受试者至少1000例，计划治疗时长不少于2年。由两名编码员对最终纳入的文献进行质量评价与结局指标提取。治疗强度参照美国心脏协会（American Heart Association, AHA）的定义进行分类。 结局指标：采用随机效应模型开展配对Meta分析与网络Meta分析（network meta-analysis, NMA），估计相对风险（relative risk, RR）与风险差（risk difference, RD）；通过I²统计量评估研究间异质性。本次分析的结局指标包括肌肉症状（任意类型肌痛、因肌肉症状导致的受试者脱落）、横纹肌溶解症以及肌酸激酶升高（超过正常上限10倍）。 结果：在2801项随机对照试验中……