While statins are known to cause musculoskeletal symptoms, the rate at which these symptoms occur appears to be lower than what has been suggested in observational studies, according to the findings of network meta-analysis (NMA) recently published in BMJ Open.

The study authors analyzed multicenter randomized controlled trials (RCTs) conducted in several countries in order to estimate the relative risk (RR) of statin-associated muscle symptoms (SAMS) based on treatment intensity. They searched PubMed, Web of Science, Cochrane database, and ClinicalTrials.gov for double-blinded RCTs that included at least 1000 patients and assessed the effect of statin therapy on lipid levels with an intended treatment period of 2 years. Final inclusion, quality, and outcomes of the articles obtained were analyzed by 2 coders.

“Pairwise and network meta-analysis estimated RR and risk difference with random effects modelling,” the authors explained. Muscle symptoms (any, myalgia, and attrition caused by muscle symptoms), rhabdomyolysis, and elevated creatinine kinase (CK; defined as >10x the upper limit of normal) were the main outcomes of the analysis.

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Of the total 2919 RCTs analyzed, 24 (n=152,461) met eligibility requirements for inclusion. Findings of the analysis revealed that patients who received high intensity statin therapy had a significantly increased risk for any muscle problem (RR, 1.04; 95% CI, 1.00-1.08; P =.031), myalgia (RR, 1.04; 95% CI, 1.00-1.08; P =.046; number needed to harm [NNH], 173), attrition caused by muscle problems (RR, 1.37; 95% CI, 1.09-1.73; P =.007; NNH, 218) and elevated CK (RR, 4.59; 95% CI, 2.32-9.10; P <.0001; NNH, 527) compared with those who received moderate intensity statins.

Results also showed a significantly increased risk for any muscle problem (RR, 1.05; 95% CI, 1.01-1.09; P =.012), myalgia (RR, 1.13; 95% CI, 1.05-1.23;P =.002; NNH, 154), attrition caused by muscle problems (RR, 1.16; 95% CI, 1.15-2.08; P =.004; NNH, 186) and elevated CK (RR, 5.25; 95% CI, 2.29-12.03; P <.00001; NNH, 589) in patients who received high intensity statin therapy compared with those who received placebo.

Estimates for rhabdomyolysis and CK were found to be inconclusive due to the inconsistency of results in the sensitivity analyses. No significant differences were observed in the risk for all other outcomes between moderate intensity statin therapy and placebo.

“We found significant but small increases in risk for patient-reported muscle problems on high-intensity statins,” the study authors concluded. “Complaints of SAMS in observational studies may be related to statin therapy or patient expectations but more likely may be due to methodological biases or the generally high prevalence of muscle problems.”


Davis JW, Weller SC. Intensity of statin therapy and muscle symptoms: a network meta-analysis of 153 000 patients. BMJ Open 2021;11:e043714. doi: 10.1136/ bmjopen-2020-043714

This article originally appeared on MPR