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Statins and skeletal muscles toxicity: from clinical trials to everyday practice.
Pharmacol Res. 2014 Oct; 88:107-13.PR

Abstract

The mechanism(s) underlying the occurrence of statin-induced myopathy are ill defined, but the results of observational studies and clinical trials provide compelling evidence that skeletal muscle toxicity is a frequent, dose-dependent, adverse event associated with all statins. It has been suggested that reduced availability of metabolites produced by the mevalonate pathway rather than intracellular cholesterol lowering per se might be the primary trigger of toxicity, however other alternative explanations have gained credibility in recent years. Aim of this review is: (i) to describe the molecular mechanisms associated to statin induced myopathy including defects in isoprenoids synthesis followed by altered prenylation of small GTPase, such as Ras and Rab proteins; (ii) to present the emerging aspects on pharmacogenetics, including CYP3A4, OATP1B1 and glycine amidinotransferase (GATM) polymorphisms impacting either statin bioavailability or creatine synthesis; (iii) to summarize the available epidemiological evidences; and (iii) to discuss the concepts that would be of interest to the clinicians for the daily management of patients with statin induced myopathy. The interplay between drug-environment and drug-drug interaction in the context of different genetic settings contribute to statins and skeletal muscles toxicity. Until specific assays/algorithms able to combine genetic scores with drug-drug-environment interaction to identify patients at risk of myopathies will become available, clinicians should continue to monitor carefully patients on polytherapy which include statins and be ready to reconsider dose, statin or switching to alternative treatments. The beneficial effects of adding agents to provide the muscle with the metabolites, such as CoQ10, affected by statin treatment will also be addressed.

Authors+Show Affiliations

Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy; Center for the Study of Atherosclerosis, Società Italiana Studio Aterosclerosi, Bassini Hospital, Cinisello Balsamo, Italy.Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy; I.R.C.C.S. Multimedica, Milan, Italy.Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy; I.R.C.C.S. Multimedica, Milan, Italy. Electronic address: alberico.catapano@unimi.it.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

24835295

Citation

Norata, Giuseppe Danilo, et al. "Statins and Skeletal Muscles Toxicity: From Clinical Trials to Everyday Practice." Pharmacological Research, vol. 88, 2014, pp. 107-13.
Norata GD, Tibolla G, Catapano AL. Statins and skeletal muscles toxicity: from clinical trials to everyday practice. Pharmacol Res. 2014;88:107-13.
Norata, G. D., Tibolla, G., & Catapano, A. L. (2014). Statins and skeletal muscles toxicity: from clinical trials to everyday practice. Pharmacological Research, 88, 107-13. https://doi.org/10.1016/j.phrs.2014.04.012
Norata GD, Tibolla G, Catapano AL. Statins and Skeletal Muscles Toxicity: From Clinical Trials to Everyday Practice. Pharmacol Res. 2014;88:107-13. PubMed PMID: 24835295.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Statins and skeletal muscles toxicity: from clinical trials to everyday practice. AU - Norata,Giuseppe Danilo, AU - Tibolla,Gianpaolo, AU - Catapano,Alberico Luigi, Y1 - 2014/05/13/ PY - 2013/11/06/received PY - 2014/04/23/revised PY - 2014/04/27/accepted PY - 2014/5/20/entrez PY - 2014/5/20/pubmed PY - 2015/4/14/medline KW - Muscle toxicity KW - Myopathy KW - Pharmacogenetics KW - Statins SP - 107 EP - 13 JF - Pharmacological research JO - Pharmacol Res VL - 88 N2 - The mechanism(s) underlying the occurrence of statin-induced myopathy are ill defined, but the results of observational studies and clinical trials provide compelling evidence that skeletal muscle toxicity is a frequent, dose-dependent, adverse event associated with all statins. It has been suggested that reduced availability of metabolites produced by the mevalonate pathway rather than intracellular cholesterol lowering per se might be the primary trigger of toxicity, however other alternative explanations have gained credibility in recent years. Aim of this review is: (i) to describe the molecular mechanisms associated to statin induced myopathy including defects in isoprenoids synthesis followed by altered prenylation of small GTPase, such as Ras and Rab proteins; (ii) to present the emerging aspects on pharmacogenetics, including CYP3A4, OATP1B1 and glycine amidinotransferase (GATM) polymorphisms impacting either statin bioavailability or creatine synthesis; (iii) to summarize the available epidemiological evidences; and (iii) to discuss the concepts that would be of interest to the clinicians for the daily management of patients with statin induced myopathy. The interplay between drug-environment and drug-drug interaction in the context of different genetic settings contribute to statins and skeletal muscles toxicity. Until specific assays/algorithms able to combine genetic scores with drug-drug-environment interaction to identify patients at risk of myopathies will become available, clinicians should continue to monitor carefully patients on polytherapy which include statins and be ready to reconsider dose, statin or switching to alternative treatments. The beneficial effects of adding agents to provide the muscle with the metabolites, such as CoQ10, affected by statin treatment will also be addressed. SN - 1096-1186 UR - https://www.unboundmedicine.com/medline/citation/24835295/Statins_and_skeletal_muscles_toxicity:_from_clinical_trials_to_everyday_practice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1043-6618(14)00052-8 DB - PRIME DP - Unbound Medicine ER -