N-of-1 (single-patient) trials for statin-related myalgia

Ann Intern Med. 2014 Mar 4;160(5):301-10. doi: 10.7326/M13-1921.

Abstract

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 placebo 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 associated with myalgia within 3 weeks of open-label use versus matching 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) participated 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.

Primary funding source: Western University, London, Ontario, Canada.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Atorvastatin
  • Double-Blind Method
  • Female
  • Fluorobenzenes / adverse effects*
  • Fluorobenzenes / therapeutic use
  • Heptanoic Acids / adverse effects*
  • Heptanoic Acids / therapeutic use
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hypercholesterolemia / drug therapy*
  • Male
  • Myalgia / chemically induced*
  • Pyrimidines / adverse effects*
  • Pyrimidines / therapeutic use
  • Pyrroles / adverse effects*
  • Pyrroles / therapeutic use
  • Research Design
  • Rosuvastatin Calcium
  • Sulfonamides / adverse effects*
  • Sulfonamides / therapeutic use

Substances

  • Fluorobenzenes
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrimidines
  • Pyrroles
  • Sulfonamides
  • Rosuvastatin Calcium
  • Atorvastatin

Associated data

  • ClinicalTrials.gov/NCT01259791