Statin-Associated Muscle Symptoms Among New Statin Users Randomly Assigned to Vitamin D or Placebo

Abstract

ImportanceStatin-associated muscle symptoms (SAMS) are common and may lead to discontinuation of indicated statin therapy. Observational studies suggest that vitamin D therapy is associated with reduced statin intolerance, but no randomized studies have been reported.ObjectiveTo test whether vitamin D supplementation was associated with prevention of SAMS and a reduction of statin discontinuation.Design, Setting, and ParticipantsMen 50 years or older and women 55 years or older, free of cancer and cardiovascular disease, were enrolled in a randomized, placebo-controlled, double-blind clinical trial of vitamin D supplementation. Participants who initiated statin therapy after randomization were surveyed in early 2016. The data were analyzed in early 2022.InterventionsDaily cholecalciferol (2000 international units) or placebo with assessment of statin prescriptions during follow-up.Main Outcomes and MeasuresMuscle pain or discomfort lasting several days (primary outcome) and discontinuation of a statin due to SAMS (secondary outcome).ResultsStatins were initiated by 1033 vitamin D–assigned participants and 1050 placebo-assigned participants; mean (SD) age was 66.8 (6.2) years and 49% were women. Over 4.8 years of follow-up, SAMS were reported by 317 participants (31%) assigned vitamin D and 325 assigned placebo (31%). The adjusted odds ratio (OR) was 0.97 (95% CI, 0.80-1.18; P = .78). Statins were discontinued by 137 participants (13%) assigned to vitamin D and 133 assigned to placebo (13%) with an adjusted OR of 1.04 (95% CI, 0.80-1.35; P = .78). These results were consistent across pretreatment 25-hydroxy vitamin D levels (interaction P value = .83). Among participants with levels less than 20 ng/mL, SAMS were reported by 28 of 85 vitamin D–assigned participants (33%) and 33 of 95 placebo-assigned participants (35%). For those with levels less than 30 ng/ml, SAMS were reported by 88 of 330 vitamin–D assigned participants (27%) and 96 of 323 of placebo-assigned participants (30%).Conclusions and RelevanceVitamin D supplementation did not prevent SAMS or reduce statin discontinuation. These results were consistent across pretreatment 25-hydroxy vitamin D levels.Trial RegistrationClinicalTrials.gov Identifier: NCT01169259