The broad spectrum of statin myopathy: from myalgia to rhabdomyolysis

Purpose of review The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are the cornerstone of therapy for dyslipidemia. A significant portion of patients are not adherent to statin therapy, due to either intolerance from muscle symptoms or fears of myopathy reported in the media. The diagnosis and management of patients with statin-induced myopathy will be reviewed. Recent findings Based on a review of healthy clinical-trial participants, the placebo-corrected incidences of minor muscle pain, myopathy (with significant elevations in creatinine kinase), and rhabdomyolysis are 190, 5, and 1.6 per 100 000 patient years, respectively. More recent prospective observational data yield better, real-world estimates of muscle complaints (>10%) in patients started on high-dose statins. Current data suggest that important patient characteristics, statin–drug pharmacokinetics, and statin–drug interactions play a role in myopathy. Myopathy is more related to statin dose and blood levels than to LDL reductions. Evidence for managing myopathic patients with coenzyme Q10 is not conclusive. Summary It is important to maintain perspective by looking at the impact of statin myopathy relative to the impact of preventing atherosclerotic complications. The potential benefits of therapy must outweigh the risks. In the case of statin therapy the benefit/risk ratio is overwhelmingly positive.

[1]  T. Lehtimäki,et al.  High‐dose statins and skeletal muscle metabolism in humans: A randomized, controlled trial , 2005, Clinical pharmacology and therapeutics.

[2]  W. H. Schaefer,et al.  Evaluation of ubiquinone concentration and mitochondrial function relative to cerivastatin-induced skeletal myopathy in rats. , 2004, Toxicology and applied pharmacology.

[3]  W. März,et al.  Risk for myopathy with statin therapy in high-risk patients. , 2003, Archives of internal medicine.

[4]  S. Dimauro,et al.  Coenzyme Q10 deficiency and isolated myopathy , 2006, Neurology.

[5]  R. Laaksonen,et al.  Decreases in serum ubiquinone concentrations do not result in reduced levels in muscle tissue during short‐term simvastatin treatment in humans , 1995, Clinical pharmacology and therapeutics.

[6]  C. Lintott,et al.  Simvastatin and side effects. , 1991, The New Zealand medical journal.

[7]  P. Mason Update on statins. , 2004, Intensive & critical care nursing.

[8]  G. Fonarow,et al.  Reduced treatment success in lipid management among women with coronary heart disease or risk equivalents: results of a national survey. , 2006, American heart journal.

[9]  P. Thompson,et al.  An assessment of statin safety by muscle experts. , 2006, The American journal of cardiology.

[10]  Marc Evans,et al.  Effects of HMG-CoA Reductase Inhibitors on Skeletal Muscle , 2002, Drug safety.

[11]  Scandinavian Simvastatin Survival Study Group Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S) , 1994, The Lancet.

[12]  A. M. Marsden,et al.  Statin-Induced Muscle Necrosis in the Rat: Distribution, Development, and Fibre Selectivity , 2005, Toxicologic pathology.

[13]  R. Subramanian,et al.  Effects of fibrates on metabolism of statins in human hepatocytes. , 2002, Drug metabolism and disposition: the biological fate of chemicals.

[14]  A. Ortiz,et al.  3-Hydroxy-3-methylglutaryl coenzyme a reductase and isoprenylation inhibitors induce apoptosis of vascular smooth muscle cells in culture. , 1998, Circulation research.

[15]  W. H. Schaefer,et al.  Statins induce apoptosis in rat and human myotube cultures by inhibiting protein geranylgeranylation but not ubiquinone. , 2004, Toxicology and applied pharmacology.

[16]  S. Grundy,et al.  ACC/AHA/NHLBI Clinical Advisory on the Use and Safety of Statins. , 2002, Circulation.

[17]  M. Maggini,et al.  The cerivastatin withdrawal crisis: a "post-mortem" analysis. , 2004, Health policy.

[18]  A. Gotto,et al.  Update on Statins: 2003 , 2004, Circulation.

[19]  R. Gregg,et al.  Inhibition of cholesterol synthesis by squalene synthase inhibitors does not induce myotoxicity in vitro. , 1997, Toxicology and applied pharmacology.

[20]  Sajda Ghani,et al.  Abstract 4193: A Randomized, Double-blind, Double-dummy, Comparison of Efficacy and Tolerability of Fluvastatin XL alone, Ezetimibe alone and the Combination, in Patients with a History of Muscle Related Side Effects with other Statins , 2006 .

[21]  J. Hallas,et al.  Lipid-Lowering Drugs and Risk of Myopathy: A Population-Based Follow-Up Study , 2001, Epidemiology.

[22]  Alicja R Rudnicka,et al.  Statin safety: a systematic review. , 2006, The American journal of cardiology.

[23]  Nikki M. Carroll,et al.  Low Myopathy Rates Associated with Statins as Monotherapy or Combination Therapy with Interacting Drugs in a Group Model Health Maintenance Organization , 2005, Pharmacotherapy.

[24]  Claude Lenfant,et al.  ACC/AHA/NHLBI clinical advisory on the use and safety of statins. , 2002, Journal of the American College of Cardiology.

[25]  J. Mckenney,et al.  Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force. , 2006, The American journal of cardiology.

[26]  Zachary Simmons,et al.  Genetic risk factors associated with lipid‐lowering drug‐induced myopathies , 2006, Muscle & nerve.

[27]  J. Stein,et al.  Outcomes in 45 patients with statin-associated myopathy. , 2005, Archives of internal medicine.

[28]  Scott Rs,et al.  Simvastatin and side effects. , 1991 .

[29]  M. Bottorff,et al.  Statin safety and drug interactions: clinical implications. , 2006, The American journal of cardiology.

[30]  D. Samid,et al.  Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer. , 1996, Clinical cancer research : an official journal of the American Association for Cancer Research.

[31]  E. Bruckert,et al.  Mild to Moderate Muscular Symptoms with High-Dosage Statin Therapy in Hyperlipidemic Patients —The PRIMO Study , 2005, Cardiovascular Drugs and Therapy.

[32]  H. Bays Statin safety: an overview and assessment of the data--2005. , 2006, The American journal of cardiology.

[33]  S. Baker Molecular clues into the pathogenesis of statin‐mediated muscle toxicity , 2005, Muscle & nerve.

[34]  A. Dirks,et al.  Statin-induced apoptosis and skeletal myopathy. , 2006, American journal of physiology. Cell physiology.

[35]  H. Brewer,et al.  Benefit-risk assessment of Rosuvastatin 10 to 40 milligrams. , 2003, The American journal of cardiology.