Incidence of muscle symptoms in placebo arm among statin-intolerant patients: a systematic review with meta-analysis

IntroductionStatins are highly used in cardiovascular prevention. Statin intolerance is the most significant cause of decreased adherence, translating into a higher cardiovascular risk. This systematic review aims to estimate the incidence of muscle adverse events in patients with a history of statin intolerance receiving placebo.MethodsDatabase search was performed in CENTRAL, MEDLINE, and EMBASE until March 2023. This systematic review included blinded randomized control trials enrolling patients with a history of statin intolerance who received a placebo. A random-effects meta-analysis was performed. Results were presented in percentages, with 95% confidence intervals (95% CI).ResultsOverall, eight studies with 8095 patients with a history of statin intolerance receiving placebo were included. The muscle adverse events incidence rate was 21.34% (95% CI 13.26-30.63%, 8 studies), and discontinuation due to adverse muscle events was 6.12% (95% CI 1.22-13.70%, 3 studies). The incidence was higher in subcutaneous placebo/sham (41.67%, 1 study) compared to oral placebo studies (22.95%, 6 studies).ConclusionIn patients previously labeled as statin-intolerant, about a fifth of the patients exhibited muscle symptoms when receiving a placebo. This highlights the importance of ruling out non-statin-related symptoms to further optimize statin therapy for cardiovascular risk improvement.