Muscle-related side-effects of statins: from mechanisms to evidence-based solutions

Purpose of review This article highlights the recent findings regarding statin-associated muscle side effects, including mechanisms and treatment as well as the need for more comprehensive clinical trials in statin myalgia. Recent findings Statin myalgia is difficult to diagnose and treat, as major clinical trials have not routinely assessed muscle sideeffects, there are few clinically relevant biomarkers and assessment tools for the symptoms, many apparent statin-related muscle symptoms may be nonspecific and related to other drugs or health conditions, and prevalence estimates vary widely. Data thus suggest that only 30–50% of patients with self-reported statin myalgia actually experience muscle pain on statins during blinded, placebo-controlled trials. In addition, evidence to date involving mechanisms underlying statin myalgia and its range of symptoms and presentations supports the hypothesis that there are multiple, interactive and potentially additive mechanisms underlying statin-associated muscle side-effects. Summary There are likely multiple and interactive mechanisms underlying statin myalgia, and recent studies have produced equivocal data regarding prevalence of statin-associated muscle side-effects, contributing factors and effectiveness of common interventions. Therefore, more clinical trials on statin myalgia are critical to the field, as are systematic resources for quantifying, predicting and reporting statin-associated muscle side-effects.

[1]  S. Guthrie,et al.  Statin use and self-reported swimming performance in US masters swimmers , 2015, Journal of sports sciences.

[2]  P. Thompson,et al.  A randomized trial of coenzyme Q10 in patients with confirmed statin myopathy. , 2015, Atherosclerosis.

[3]  G. Lip,et al.  Analysis of vitamin D levels in patients with and without statin-associated myalgia - a systematic review and meta-analysis of 7 studies with 2420 patients. , 2015, International journal of cardiology.

[4]  A. Sahebkar,et al.  Effects of coenzyme Q10 on statin-induced myopathy: a meta-analysis of randomized controlled trials. , 2015, Mayo Clinic proceedings.

[5]  S. Bertisch,et al.  Vitamin D status modifies the association between statin use and musculoskeletal pain: a population based study. , 2015, Atherosclerosis.

[6]  J. Armitage,et al.  Pharmacogenomics of statin therapy: any new insights in efficacy or safety? , 2014, Current opinion in lipidology.

[7]  M. Lunder,et al.  Coenzyme Q10 Supplementation Decreases Statin-Related Mild-to-Moderate Muscle Symptoms: A Randomized Clinical Study , 2014, Medical science monitor : international medical journal of experimental and clinical research.

[8]  P. Thompson,et al.  Changes in muscle strength in patients with statin myalgia. , 2014, The American journal of cardiology.

[9]  Oladimeji Akinboro,et al.  N-of-1 (Single-Patient) Trials for Statin-Related Myalgia , 2014, Annals of Internal Medicine.

[10]  M. Tarnopolsky,et al.  Statin-associated Autoimmune Myopathies: A Pathophysiologic Spectrum , 2014, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[11]  M. Schwab,et al.  Mechanisms and assessment of statin‐related muscular adverse effects , 2014, British journal of clinical pharmacology.

[12]  C. Cooper,et al.  ACE inhibitors, statins and thiazides: no association with change in grip strength among community dwelling older men and women from the Hertfordshire Cohort Study. , 2014, Age and ageing.

[13]  P. Thompson,et al.  A systematic review of statin-induced muscle problems in clinical trials. , 2014, American heart journal.

[14]  G. Watts,et al.  Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab. , 2014, Journal of the American College of Cardiology.

[15]  P. Savage,et al.  Statin therapy does not attenuate exercise training response in cardiac rehabilitation. , 2014, Journal of the American College of Cardiology.

[16]  K. Mergenhagen,et al.  Low vitamin D as a risk factor for the development of myalgia in patients taking high-dose simvastatin: a retrospective review. , 2014, Clinical therapeutics.

[17]  R. Rosenson,et al.  An assessment by the Statin Muscle Safety Task Force: 2014 update. , 2014, Journal of clinical lipidology.

[18]  A. Porter,et al.  Low plasma vitamin D levels and muscle-related adverse effects in statin users. , 2014, The Israel Medical Association journal : IMAJ.

[19]  Michael J Pencina,et al.  Application of new cholesterol guidelines to a population-based sample. , 2014, The New England journal of medicine.

[20]  P. Thompson,et al.  Increases in creatine kinase with atorvastatin treatment are not associated with decreases in muscular performance. , 2013, Atherosclerosis.

[21]  Matthew K Ito,et al.  Predictors of statin adherence, switching, and discontinuation in the USAGE survey: understanding the use of statins in America and gaps in patient education. , 2013, Journal of clinical lipidology.

[22]  S. Hazen,et al.  Treatment strategies in patients with statin intolerance: the Cleveland Clinic experience. , 2013, American heart journal.

[23]  P. Fadel,et al.  Simvastatin impairs exercise training adaptations. , 2013, Journal of the American College of Cardiology.

[24]  P. Thompson,et al.  A randomized trial of coenzyme Q10 in patients with statin myopathy: rationale and study design. , 2013, Journal of clinical lipidology.

[25]  Alexander Turchin,et al.  Accuracy of Electronically Reported “Meaningful Use” Clinical Quality Measures , 2013, Annals of Internal Medicine.

[26]  U. Malt,et al.  No effect of combined coenzyme Q10 and selenium supplementation on atorvastatin-induced myopathy , 2013, Scandinavian cardiovascular journal : SCJ.

[27]  J. Fedačko,et al.  Coenzyme Q(10) and selenium in statin-associated myopathy treatment. , 2013, Canadian journal of physiology and pharmacology.

[28]  P. Thompson,et al.  Effect of Statins on Skeletal Muscle Function , 2012, Circulation.

[29]  C. Lavie,et al.  Impact of Coenzyme Q-10 on Parameters of Cardiorespiratory Fitness and Muscle Performance in Older Athletes Taking Statins , 2012, The Physician and sportsmedicine.

[30]  Christos Hatzigeorgiou,et al.  Effect of coenzyme Q10 supplementation on statin-induced myalgias. , 2012, The American journal of cardiology.

[31]  H. Halkin,et al.  Muscle pain and serum creatine kinase are not associated with low serum 25(OH) vitamin D levels in patients receiving statins , 2012, Clinical endocrinology.

[32]  P. Thompson,et al.  The relationship of vitamin D deficiency to statin myopathy. , 2011, Atherosclerosis.

[33]  P. Thompson,et al.  The effects of statins on skeletal muscle strength and exercise performance , 2010, Current opinion in lipidology.

[34]  B. Golomb,et al.  Statin‐Associated Muscle‐Related Adverse Effects: A Case Series of 354 Patients , 2010, Pharmacotherapy.

[35]  P. Thompson,et al.  The genetics of statin-induced myopathy. , 2010, Atherosclerosis.

[36]  Joanna M. Young,et al.  Effect of coenzyme Q(10) supplementation on simvastatin-induced myalgia. , 2007, The American journal of cardiology.

[37]  P. Thompson,et al.  The role of coenzyme Q10 in statin-associated myopathy: a systematic review. , 2007, Journal of the American College of Cardiology.

[38]  M. McNurlan,et al.  Effect of coenzyme q10 on myopathic symptoms in patients treated with statins. , 2007, The American journal of cardiology.

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

[40]  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.

[41]  E. Hoffman,et al.  Changes in Ubiquitin Proteasome Pathway Gene Expression in Skeletal Muscle With Exercise and Statins , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[42]  L. Teichholz Statin-associated myopathy with normal creatine kinase levels. , 2003, Annals of internal medicine.

[43]  A. Gotto,et al.  Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. , 1998, JAMA.

[44]  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.

[45]  J. E. Pedersen,et al.  Inhalation of levomepromazine in severe acute asthma , 1994, The Lancet.