CPIC UPdate nature publishing group Cytochrome P450 (CYP)2C19 catalyzes the bioactivation of the antiplatelet prodrug clopidogrel, and CYP2C19 loss-of-function alleles impair formation of active metabolites, resulting in reduced platelet inhibition. In addition, CYP2C19 loss-of-function alleles confer increased risks for serious adverse cardiovascular (CV) events among clopidogrel-treated patients with acute coronary syndromes (ACSs) undergoing percutaneous coronary intervention (PCI). Guideline updates include emphasis on appropriate indication for CYP2C19 genotype–directed antiplatelet therapy, refined recommendations for specific CYP2C19 alleles, and additional evidence from an expanded literature review (updates at http://m.wendangku.net/doc/25f8d86571fe910ef02df87d.html ).
This document is an update to the 2011 Clinical Pharmacogenetics Implementation Consortium (CPIC) guide-line on the clinical use of CYP2C19 genotype test results for patients requiring antiplatelet therapy.1 As of April 2013, a pro-spective randomized controlled trial on CYP2C19 genotype–directed antiplatelet therapy with clinical outcomes has yet to be reported. Consequently, these recommendations are based on evaluation of the currently available evidence. Specifically, the updated therapeutic recommendations are more focused on patients with acute coronary syndromes (ACSs) undergo-ing percutaneous coronary intervention (PCI) than the original guideline, with additional updates involving refined recommen-dations for variant and novel CYP2C19 alleles beyond *2 and further evidence from an expanded literature review. As in the 2011 guideline, recommendations for the use of other laboratory tests, such as platelet function monitoring, and cost-effectiveness assessments are beyond the scope of this document. This docu-ment does not focus on demographic or other clinical variables such as adherence to therapy, age, diabetes mellitus, obesity, smoking, and concomitant use of other drugs that may influence clopidogrel efficacy and clinical decision making. The CPIC of the National Institutes of Health’s Pharmacogenomics Research Network and PharmGKB develops peer-reviewed gene/drug guidelines that are published and updated on http://m.wendangku.net/doc/25f8d86571fe910ef02df87d.html every 2 years or as needed based on significant developments in the field.2FOCUSED LITERATURE REVIEW A systematic literature review was conducted on CYP2C19 geno-type and clopidogrel response (see Supplementary Materials and Methods online). Guidelines for antiplatelet therapy were developed based on interpretation of the available literature by the authors and experts in the field.DRUG: CLOPIDOGREL Background Clopidogrel is a thienopyridine prodrug that requires hepatic biotransformation to form an active metabolite that selectively and irreversibly inhibits the purinergic P2RY 12 receptor and thus platelet aggregation for the platelet’s life span (~10 days). Received 28 February 2013; accepted 6 May 2013; advance online publication 24 July 2013. doi:10.1038/clpt.2013.105
Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C19 Genotype and Clopidogrel Therapy: 2013 Update
SA Scott 1, K Sangkuhl 2, CM Stein 3, J-S Hulot 4,5, JL Mega 6, DM Roden 7, TE Klein 2, MS Sabatine 6, JA Johnson 8,9,10 and AR Shuldiner 11,12
1Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA; 2Department of Genetics, Stanford University,
Stanford, California, USA; 3Division of Clinical Pharmacology, Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA; 4Department of Pharmacology, Université Pierre et Marie Curie-Paris 6, INSERM UMR S 956, Pitié-Salpêtrière University Hospital, Paris, France; 5Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA; 6Thrombolysis in Myocardial Infarction (TIMI) Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA; 7Department of Medicine and Pharmacology, Office of Personalized Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA; 8Department of Pharmacotherapy and Translational Research, Colleges of Pharmacy and Medicine, Gainesville, Florida, USA; 9Center for Pharmacogenomics, University of Florida, Gainesville, Florida, USA; 10Department of Medicine (Cardiology), Colleges of Pharmacy and Medicine, University of Florida, Gainesville, Florida, USA; 11Department of Medicine and Program for Genomic and Personalized Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA; 12Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, Maryland, USA. Correspondence: AR Shuldiner (email@example.com )
CliniCal pharmaCology & TherapeuTiCs | VOLUME 94 NUMBER 3 | SEPTEMBER 2013 http://m.wendangku.net/doc/25f8d86571fe910ef02df87d.html