Phenotype standardization for statin-induced myotoxicity

doi:10.1038/clpt.2014.121

. 2014 Oct;96(4):470-6.

doi: 10.1038/clpt.2014.121. Epub 2014 Jun 4.

Phenotype standardization for statin-induced myotoxicity

A Alfirevic¹, D Neely², J Armitage³, H Chinoy⁴, R G Cooper⁵, R Laaksonen⁶, D F Carr¹, K M Bloch¹, J Fahy¹, A Hanson¹, Q-Y Yue⁷, M Wadelius⁸, A H Maitland-van Der Zee⁹, D Voora¹⁰, B M Psaty¹¹, C N A Palmer¹², M Pirmohamed¹

Affiliations

¹ Department of Molecular and Clinical Pharmacology, TheWolfson Centre for Personalised Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
² Department of Clinical Biochemistry, Newcastle upon Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary, Newcastle upon Tyne, UK.
³ Clinical Trial Service Unit, Oxford, UK.
⁴ Centre for Musculoskeletal Research/NIHR Manchester Musculoskeletal Biomedical Research Unit, University of Manchester, Manchester, UK.
⁵ MRC/ARUK Institute of Ageing and Chronic Disease, Faculty of Health & Life Sciences, University of Liverpool, Liverpool, UK.
⁶ Zora Biosciences Ltd, Tieotie 2, Espoo, Finland.
⁷ The Medical Products Agency, Uppsala, Sweden.
⁸ Department of Medical Sciences, Clinical Pharmacology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
⁹ Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands.
¹⁰ Duke Institute for Genome Sciences and Policy, Durham, North Carolina, USA.
¹¹ 1] Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, Washington, USA [2] Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USA.
¹² Medical Research Institute, Ninewells Hospital and Medical School, Dundee, UK.

PMID: 24897241
PMCID: PMC4172546
DOI: 10.1038/clpt.2014.121

Phenotype standardization for statin-induced myotoxicity

A Alfirevic et al. Clin Pharmacol Ther. 2014 Oct.

. 2014 Oct;96(4):470-6.

doi: 10.1038/clpt.2014.121. Epub 2014 Jun 4.

Authors

Affiliations

¹ Department of Molecular and Clinical Pharmacology, TheWolfson Centre for Personalised Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
² Department of Clinical Biochemistry, Newcastle upon Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary, Newcastle upon Tyne, UK.
³ Clinical Trial Service Unit, Oxford, UK.
⁴ Centre for Musculoskeletal Research/NIHR Manchester Musculoskeletal Biomedical Research Unit, University of Manchester, Manchester, UK.
⁵ MRC/ARUK Institute of Ageing and Chronic Disease, Faculty of Health & Life Sciences, University of Liverpool, Liverpool, UK.
⁶ Zora Biosciences Ltd, Tieotie 2, Espoo, Finland.
⁷ The Medical Products Agency, Uppsala, Sweden.
⁸ Department of Medical Sciences, Clinical Pharmacology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
⁹ Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands.
¹⁰ Duke Institute for Genome Sciences and Policy, Durham, North Carolina, USA.
¹¹ 1] Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, Washington, USA [2] Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USA.
¹² Medical Research Institute, Ninewells Hospital and Medical School, Dundee, UK.

PMID: 24897241
PMCID: PMC4172546
DOI: 10.1038/clpt.2014.121

Abstract

Statins are widely used lipid-lowering drugs that are effective in reducing cardiovascular disease risk. Although they are generally well tolerated, they can cause muscle toxicity, which can lead to severe rhabdomyolysis. Research in this area has been hampered to some extent by the lack of standardized nomenclature and phenotypic definitions. We have used numerical and descriptive classifications and developed an algorithm to define statin-related myotoxicity phenotypes, including myalgia, myopathy, rhabdomyolysis, and necrotizing autoimmune myopathy.

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Figures

**Figure 1**
Algorithm for defining the type of statin-related myotoxicity. New nomenclature was introduced to reflect the phenotype classification and severity (SRM 0 to SRM 6) of statin-related toxicity. CK, creatine kinase; HMGCR, 3-hydroxy-3-methylglutaryl-coenzyme A reductase; LLD, lipid-lowering drug; SRM, statin-related myotoxicity; ULN, upper limit of normal.

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References

1. Law M., Rudnicka A.R. Statin safety: a systematic review. Am. J. Cardiol. 2006;97:52C–60C. - PubMed
1. Sathasivam S. Statin induced myotoxicity. Eur. J. Intern. Med. 2012;23:317–324. - PubMed
1. Stone N.J., et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Circulation 2013. e-pub ahead of print 12 November 2013. - PubMed
1. Graham D.J., et al. Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA. 2004;292:2585–2590. - PubMed
1. Staffa J.A., Chang J., Green L. Cerivastatin and reports of fatal rhabdomyolysis. N. Engl. J. Med. 2002;346:539–540. - PubMed

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[1] Law M., Rudnicka A.R. Statin safety: a systematic review. Am. J. Cardiol. 2006;97:52C–60C. - PubMed

[2] Law M., Rudnicka A.R. Statin safety: a systematic review. Am. J. Cardiol. 2006;97:52C–60C. - PubMed

[3] Sathasivam S. Statin induced myotoxicity. Eur. J. Intern. Med. 2012;23:317–324. - PubMed

[4] Sathasivam S. Statin induced myotoxicity. Eur. J. Intern. Med. 2012;23:317–324. - PubMed

[5] Stone N.J., et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Circulation 2013. e-pub ahead of print 12 November 2013. - PubMed

[6] Stone N.J., et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Circulation 2013. e-pub ahead of print 12 November 2013. - PubMed

[7] Graham D.J., et al. Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA. 2004;292:2585–2590. - PubMed

[8] Graham D.J., et al. Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA. 2004;292:2585–2590. - PubMed

[9] Staffa J.A., Chang J., Green L. Cerivastatin and reports of fatal rhabdomyolysis. N. Engl. J. Med. 2002;346:539–540. - PubMed

[10] Staffa J.A., Chang J., Green L. Cerivastatin and reports of fatal rhabdomyolysis. N. Engl. J. Med. 2002;346:539–540. - PubMed

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Phenotype standardization for statin-induced myotoxicity

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Phenotype standardization for statin-induced myotoxicity

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