The addition of the cholesterol-lowering drug ezetimibe to simvastatin in patients with a recent acute coronary syndrome was not found to be associated with an increased incidence of patient-reported muscle complaints or major muscle events, according to an analysis published in the Journal of the American College of Cardiology.

This is an analysis of the IMPROVE-IT randomized trial, in which patients hospitalized after an acute coronary syndrome were randomly assigned to receive simvastatin 40 mg plus placebo or ezetimibe plus simvastatin 40 mg without run-in. This analysis focused on the rates of patient-reported muscle complaints and adjudicated major muscle events. Only patients who took ≥1 dose of the study drug were included in this analysis (n=17,706). At each visit, participants were asked about any muscle complaints.

Over an 84-month follow-up period, the rate of muscle complaints was found to be comparable in patients taking simvastatin alone or in combination with ezetimibe (18.0% vs 18.7%, respectively). The time to first serious muscle event and the rates of major muscle events were also comparable in the 2 groups (simvastatin monotherapy, 0.62%; ezetimibe plus simvastatin, 0.53%).

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Factors associated with a lower incidence of muscle complaints included older age (hazard ratio [HR], 0.91 per 5 years starting at age 65; 95% CI, 0.88-0.95) and diabetes (HR, 0.86; 95% CI, 0.79-0.94). Factors associated with an increased incidence of muscle complaints included female sex (HR, 1.29; 95% CI, 1.18-1.40), inflammatory disease (HR, 1.24; 95% CI, 1.10-1.40), elevated baseline creatine kinase (HR, 1.04 per 10 U/L up to 90 U/L; 95% CI, 1.02-1.05), and body mass index (HR, 1.08 per 5 kg/m2; 95% CI, 1.04-1.11).

 “Our findings…should reassure clinicians and patients that the addition of ezetimibe to statin therapy does not increase muscle-related side-effects,” noted the study authors.

Disclosure: This clinical trial was supported by Merck. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Nanna MG, Navar AM, Giugliano RP, et al. Muscle complaints or events in patients randomized to simvastatin or ezetimibe/simvastatin. J Am Coll Cardiol. 2020;75(7):835-837.