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.