N-of-1 Trials for Myalgia in People Taking a Statin

Abstract

About 1 in 5 patients taking statins report some degree of muscular pain or other musculoskeletal symptom, but there is great controversy over what proportion is due to statin therapy. This uncertainty has considerable clinical significance, given the importance of adherence to statins and the increasing number of therapies available for statin intolerance. N-of-1 trials provide the most reliable assessment of causality for an individual person. However, only 8 N-of-1 trials have been reported for patients with possible statin-related myalgia, and for all 8 there was no evidence that the statin was causal 1DOI:10.7326/M13-19211DOI:10.7326/M13-1921. This study aims to evaluate the feasibility and sustainability of an information technology-enhanced N-of-1 trial service to improve the diagnosis of statin-induced myalgia in Australian general practice setting. N-of-1 (single-patient multiple crossover) trials (n = 15) of patients with prior history of intolerance of both atorvastatin 10 mg and rosuvastatin 5 mg monotherapy, who had myalgia occurring within three weeks of starting statin therapy and consequently discontinued statin use. Each person will go through 3 double-blind, crossover comparisons of statin versus matching placebo for a total of 27 weeks. Myalgia scores and Brief Pain Inventory Questionnaire will be recorded on a weekly basis during the study period. Blood sample collection will be done at baseline and at the end of each active treatment and control period to measure serum CK, ALT, AST, FGF21 and creatinine levels. To avoid unblinding of treatment allocation during the trial period, additional blood samples will be stored to measure lipid levels upon study completion. Genotype analysis will also be done at the end of the study to determine if genotype is associated with statin-induced myalgia. Patient and prescriber intentions to continue statin therapy at the end of the trial will also be assessed.