Toward "pain-free" statin prescribing: clinical algorithm for diagnosis and management of myalgia

Mayo Clin Proc. 2008 Jun;83(6):687-700. doi: 10.4065/83.6.687.


Myalgia, which often manifests as pain or soreness in skeletal muscles, is among the most salient adverse events associated with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). Clinical issues related to statin-associated myotoxicity include (1) incidence in randomized controlled trials and occurrence in postmarketing surveillance databases; (2) potential differences between statins in their associations with such adverse events; and (3) diagnostic and treatment strategies to prevent, recognize, and manage these events. Data from systematic reviews, meta-analyses, clinical and observational trials, and post-marketing surveillance indicate that statin-associated myalgia typically affects approximately 5.0% of patients, as myopathy in 0.1% and as rhabdomyolysis in 0.01%. However, studies also suggest that myalgia is among the leading reasons patients discontinue statins (particularly high-dose statin monotherapy) and that treatment with certain statins (eg, fluvastatin) is unlikely to result in such adverse events. This review presents a clinical algorithm for monitoring and managing statin-associated myotoxicity. The algorithm highlights risk factors for muscle toxicity and provides recommendations for (1) creatine kinase measurements and monitoring; (2) statin dosage reduction, discontinuation, and rechallenge; and (3) treatment alternatives, such as extended-release fluvastatin with or without ezetimibe, low-dose or alternate-day rosuvastatin, or ezetimibe with or without colesevelam. The algorithm should help to inform and enhance patient care and reduce the risk of myalgia and other potentially treatment-limiting muscle effects that might undermine patient adherence and compromise the overall cardioprotective benefits of statins.

Publication types

  • Review

MeSH terms

  • Algorithms
  • Clinical Trials as Topic
  • Creatine Kinase / blood
  • Fibromyalgia* / chemically induced
  • Fibromyalgia* / diagnosis
  • Fibromyalgia* / therapy
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Kaplan-Meier Estimate
  • Meta-Analysis as Topic
  • Product Surveillance, Postmarketing
  • Rhabdomyolysis* / blood
  • Rhabdomyolysis* / chemically induced
  • Rhabdomyolysis* / physiopathology
  • Risk Factors


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Creatine Kinase