N-of-1 (Single-Patient) Trials for Statin-Related Myalgia

Background: Statin-related myalgia is difficult to distinguish from other conditions causing myalgia and may often lead to statin discontinuation. Objective: To compare the effect of statin rechallenge with pla-cebo in patients with prior statin-related myalgia and to determine whether patients resumed statin therapy after evaluating the results. Design: N-of-1 trial with 3 double-blind, crossover comparisons separated by 3-week washout periods. (Clinicaltrials.gov: NCT01259791) Setting: Tertiary care lipid clinic. Patients: Patients with prior statin-related myalgia with or without mild elevation of creatine kinase levels. Intervention: Rechallenge with the statin that was previously asso-ciated with myalgia within 3 weeks of open-label use versus match-ing placebo. Measurements: Weekly visual analogue scale (VAS) scores for myalgia and specific symptoms (VAS myalgia score and symptom-specific VAS score, respectively), pain interference scores, and pain severity scores were recorded during the 3-week periods when patients were receiving placebo or statin. The primary outcome was the VAS myalgia score (range, 0 to 100 mm). Results: Eight patients (mean age, 66 years [SD, 8 years]; 88% women, all with high 10-year Framingham cardiovascular risk) par-ticipated in n-of-1 trials. Seven patients completed 3 treatment pairs, and 1 completed 2 treatment pairs. For each n-of-1 trial, no statistically significant differences were seen between statin and placebo in the VAS myalgia score, symptom-specific VAS score, pain interference score, and pain severity score. Five patients resumed open-label statin treatment, with a median posttrial follow-up of 10 months. Limitation: Results are limited by the small sample size and cannot be extended to patients with longer onset of myalgia after statin initiation. Conclusion: In selected patients with a history of statin-related myalgia whose symptoms are difficult to evaluate, n-of-1 trials may be a useful method for determining statin tolerability