Vitamin D supplementation or statin discontinuation fails to prevent muscle symptoms in statin users: JAMA

The 2083 participants in a double-blind, randomized trial of vitamin D supplementation who initiated statin therapy during follow-up and responded to a survey were equally likely to discontinue statin therapy (13% vs 13%) and develop muscle symptoms (31% vs 31%), whether assigned to vitamin D or placebo.

Statin-associated muscle symptoms are frequent and may result in the discontinuation of indicated statin therapy. Observational studies indicate that vitamin D therapy is linked with reduced statin tolerance, but no randomized studies have been reported. Therefore, Mark A. Hlatky, Stanford University School of Medicine, Stanford, California, and colleagues aimed to test whether vitamin D supplementation was linked with SAMS prevention and a reduction of statin discontinuation.

In early 2016, a survey was done of participants who initiated statin therapy. For this purpose, the researchers enrolled women 55 or older or men 50 years or older, free of cardiovascular disease and cancer, in a placebo-controlled, randomized, and double-blind clinical trial of vitamin D supplementation. Data analysis was done in early 2022.

The participants' received daily cholecalciferol (2000 international units) or placebo and were assessed for statin prescriptions during follow-up. The primary outcome was muscle pain or discomfort lasting several days, and the secondary outcome was the discontinuation of a statin due to SAMS.

The study led to the following findings:

• Statins were initiated by 1033 vitamin D–assigned participants and 1050 placebo-assigned participants; the mean age was 66.8 years, and 49% were women.
• Over 4.8 years of follow-up, SAMS was reported by 31% assigned vitamin D and 31% given a placebo. The adjusted odds ratio (OR) was 0.97.
• Statins were discontinued by 13% of participants assigned to vitamin D and 133 assigned to placebo (13%) with an adjusted OR of 1.04.
• These results were consistent across pretreatment 25-hydroxy vitamin D levels.
• 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 was reported by 88 of 330 vitamin–D assigned participants (27%) and 96 of 323 placebo-assigned participants (30%).

"Supplementation of vitamin D did not prevent SAMS or reduce statin discontinuation," the researchers wrote. "These findings were consistent across pretreatment 25-hydroxy vitamin D levels."

Reference:

Hlatky MA, Gonzalez PE, Manson JE, et al. Statin-Associated Muscle Symptoms Among New Statin Users Randomly Assigned to Vitamin D or Placebo. JAMA Cardiol. Published online November 23, 2022. doi:10.1001/jamacardio.2022.4250