Statin treatment and muscle symptoms: series of randomised, placebo controlled n-of-1 trials.

Abstract (PubMed)

OBJECTIVE: To establish the effect of statins on muscle symptoms in people who had previously reported muscle symptoms when taking statins. DESIGN: Series of randomised, placebo controlled n-of-1 trials. SETTING: Primary care across 50 sites in the United Kingdom, December 2016 to April 2018. PARTICIPANTS: 200 participants who had recently stopped or were considering stopping treatment with statins because of muscle symptoms. INTERVENTIONS: Participants were randomised to a sequence of six double blind treatment periods of two months each, alternating between atorvastatin 20 mg/day and placebo. MAIN OUTCOME MEASURES: The primary outcome was the mean within-person difference in muscle symptom score (scale 0-10) between statin and placebo periods. RESULTS: Of the 200 participants, 151 (76%) were included in the primary analysis. The mean within-person difference in muscle symptom score between statin and placebo periods was -0.11 (99% CI -0.36 to 0.14; P=0.40). Withdrawals due to intolerable symptoms occurred in 18 (9%) participants in statin periods versus 13 (7%) in placebo periods (rate ratio 1.38; 99% CI 0.66 to 2.83; P=0.56). No overall effect of statins on muscle symptoms was found in this population. Two thirds of completers decided to restart statins after receiving their individual trial results. CONCLUSIONS: The finding of no overall effect of statins on muscle symptoms in a population selected for previous experience of muscle symptoms when taking statins is consistent with a nocebo effect as an explanation for most reports of statin-related muscle symptoms in clinical practice.