The Role of Exercise in Statin-Associated Muscle Symptoms Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Objective: To provide a synthesis of randomized controlled trials (RCTs) investigating statin-associated muscle symptoms (SAMS) in adults who underwent exercise training intervention. Patients and Methods: We systematically searched 5 electronic databases for placebo-controlled RCTs through January 31, 2023. We included short-term and long-term exercise interventions that compared the efficacy and safety of exercise+statin vs exercise+placebo in healthy adults and reported SAMS preintervention and postintervention. Publication bias and methodological study quality assessments were performed. Results: Five of 454 potentially qualifying RCTs met the inclusion criteria, all short-term exercise RCTs. Participants were predominantly physically inactive young to middle-aged (M=37.2 y) men (57%), 252 (49%) who were on statin therapy, and 271 (53%) on placebo. Of the 3 RCTs providing qualitative SAMS results, 19 (9%) out of 220 participants reported SAMS on exercise+statin and 10 (4%) out of 234 reported SAMS on exercise+placebo. There was no difference between exercise+statin vs exercise+placebo for maximal oxygen consumption (d=−0.18; 95% CI, −0.37 to 0.00; P=.06) or creatine kinase after short-term exercise (d=0.59; 95% CI, −0.06 to 1.25; P=.08). Participants in the exercise+statin group reduced low-density lipoprotein cholesterol vs exercise+placebo (d=−1.84; 95% CI, −2.28 to −1.39; P<.001). Most of the RCTs exhibited low levels of risk of bias (k=4, 80%) and achieved moderate methodological study quality (75.0%±5.2%). Conclusion: Self-reported SAMs tended to be 5% greater after short-term exercise in statin users compared with placebo, although this difference did not achieve statistical significance. There remains an important need for placebo-controlled RCTs investigating the prevalence of statin-induced SAMS during exercise training.