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

JAMA Cardiol. 2023 Jan 1;8(1):74-80. doi: 10.1001/jamacardio.2022.4250.

Abstract

Importance: Statin-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.

Objective: To test whether vitamin D supplementation was associated with prevention of SAMS and a reduction of statin discontinuation.

Design, setting, and participants: Men 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.

Interventions: Daily cholecalciferol (2000 international units) or placebo with assessment of statin prescriptions during follow-up.

Main outcomes and measures: Muscle pain or discomfort lasting several days (primary outcome) and discontinuation of a statin due to SAMS (secondary outcome).

Results: Statins 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 relevance: Vitamin D supplementation did not prevent SAMS or reduce statin discontinuation. These results were consistent across pretreatment 25-hydroxy vitamin D levels.

Trial registration: ClinicalTrials.gov Identifier: NCT01169259.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Cholecalciferol / therapeutic use
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / adverse effects
  • Male
  • Muscles
  • Vitamin D / therapeutic use
  • Vitamins / therapeutic use

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Vitamin D
  • Vitamins
  • Cholecalciferol

Associated data

  • ClinicalTrials.gov/NCT01169259