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...