Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C19 Genotype and Clopidogrel Therapy: 2013 Update
Stuart A. Scott,Katrin Sangkuhl,Charles M. Stein,Jean-Sébastien Hulot,Jean-Sébastien Hulot,Jessica L. Mega,Dan M. Roden,Teri E. Klein,Marc S. Sabatine,Julie A. Johnson,Julie A. Johnson,Alan R. Shuldiner,Alan R. Shuldiner +12 more
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TLDR
In this article, an expanded literature review showed that 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).Abstract:
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://www.pharmgkb.org).read more
Citations
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Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors
JK Hicks,Jeffrey R. Bishop,Katrin Sangkuhl,Daniel J. Müller,Yuan Ji,SG Leckband,J. S. Leeder,Rebecca L. Graham,DL Chiulli,Adrián LLerena,Todd C. Skaar,Stuart A. Scott,Julia C. Stingl,Teri E. Klein,Kelly E. Caudle,Andrea Gaedigk +15 more
TL;DR: Evidence from the published literature supporting associations between CYP2D6 and CYC19 polymorphisms and SSRIs efficacy and safety is summarized and dosing recommendations for fluvoxamine, paroxetine, citalopram, escitaloprams, and sertraline based on CYP1C19 genotype are provided.
Journal ArticleDOI
Clinical Interpretation and Implications of Whole-Genome Sequencing
Frederick E. Dewey,Megan E. Grove,Cuiping Pan,Benjamin A. Goldstein,Jonathan A. Bernstein,Hassan Chaib,Jason D. Merker,Rachel L. Goldfeder,Gregory M. Enns,Sean P. David,Neda Pakdaman,Kelly E. Ormond,Colleen Caleshu,Kerry Kingham,Teri E. Klein,Michelle Whirl-Carrillo,Kenneth Sakamoto,Matthew T. Wheeler,Atul J. Butte,James M. Ford,Linda M. Boxer,John P. A. Ioannidis,Alan C. Yeung,Alan C. Yeung,Russ B. Altman,Themistocles L. Assimes,Themistocles L. Assimes,Michael Snyder,Michael Snyder,Euan A. Ashley,Thomas Quertermous +30 more
TL;DR: The use of WGS was associated with incomplete coverage of inherited disease genes, low reproducibility of detection of genetic variation with the highest potential clinical effects, and uncertainty about clinically reportable findings.
Journal ArticleDOI
Preemptive Clinical Pharmacogenetics Implementation: Current Programs in Five US Medical Centers
Henry M. Dunnenberger,Kristine R. Crews,James M. Hoffman,Kelly E. Caudle,Ulrich Broeckel,Scott C. Howard,Robert J. Hunkler,Teri E. Klein,William E. Evans,Mary V. Relling +9 more
TL;DR: Current programs that use preemptive genotyping to optimize the pharmacotherapy of patients are discussed and key processes for implementation are highlighted, including clinical decision support.
Journal ArticleDOI
Updated Expert Consensus Statement on Platelet Function and Genetic Testing for Guiding P2Y12 Receptor Inhibitor Treatment in Percutaneous Coronary Intervention
Dirk Sibbing,Daniel Aradi,Dimitrios Alexopoulos,Jurriën M. ten Berg,Deepak L. Bhatt,Laurent Bonello,Jean-Philippe Collet,Thomas Cuisset,Francesco Franchi,Lisa Gross,Paul A. Gurbel,Young-Hoon Jeong,Roxana Mehran,David J. Moliterno,Franz-Josef Neumann,Naveen L. Pereira,Matthew J. Price,Marc S. Sabatine,Derek So,Gregg W. Stone,Robert F. Storey,Udaya S. Tantry,Dietmar Trenk,Marco Valgimigli,Ron Waksman,Dominick J. Angiolillo +25 more
TL;DR: An international expert consensus group of key leaders from North America, Asia, and Europe with expertise in the field of antiplatelet treatment was convened and summarizes the contemporary updated expert consensus recommendations for the selective use of PFT or genotyping in patients undergoing percutaneous coronary intervention.
Journal ArticleDOI
Incorporation of Pharmacogenomics into Routine Clinical Practice: the Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline Development Process
Kelly E. Caudle,Teri E. Klein,James M. Hoffman,Daniel J. Müller,Michelle Whirl-Carrillo,Li Gong,Ellen M. McDonagh,Katrin Sangkuhl,Caroline F. Thorn,Matthias Schwab,Matthias Schwab,José A. G. Agúndez,Robert R. Freimuth,Vojtech Huser,Ming Ta Michael Lee,Ming Ta Michael Lee,Otito F. Iwuchukwu,Kristine R. Crews,Stuart A. Scott,Mia Wadelius,Jesse J. Swen,Rachel F. Tyndale,C. Michael Stein,Dan M. Roden,Mary V. Relling,Marc S. Williams,Samuel G. Johnson +26 more
TL;DR: This paper reviews the development process of the CPIC guidelines and compares this process to the Institute of Medicine’s Standards for Developing Trustworthy Clinical Practice Guidelines.
References
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Journal Article
Differences in the incidence of the CYP2C19 polymorphism affecting the S-mephenytoin phenotype in Chinese Han and Bai populations and identification of a new rare CYP2C19 mutant allele.
Zhousheng Xiao,Joyce A. Goldstein,Hong-Guang Xie,Joyce Blaisdell,Wei Wang,Chang-Hong Jiang,Feng-Xiang Yan,Nan He,Song-Ling Huang,Zhen-Hua Xu,Hong-Hao Zhou +10 more
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Cytochrome P450 2C19*2 polymorphism and cardiovascular recurrences in patients taking clopidogrel: a meta-analysis.
Francesco Sofi,Betti Giusti,Rossella Marcucci,Anna Maria Gori,Rosanna Abbate,Gian Franco Gensini +5 more
TL;DR: A meta-analysis of all the prospective studies that have been published, carried out on nearly 8000 patients with CAD undergoing clopidogrel treatment, shows that the CYP2C19*2 polymorphism is associated with an increased risk of major adverse cardiovascular events and stent thrombosis.
Journal ArticleDOI
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TL;DR: This PharmGKB summary briefly discusses the CYP2C19 gene and current understanding of its function, regulation, and pharmacogenomic relevance.
Journal ArticleDOI
Protective effect of the CYP2C19 *17 polymorphism with increased activation of clopidogrel on cardiovascular events
Klaus Tiroch,Dirk Sibbing,Werner Koch,Tobias Roosen-Runge,Julinda Mehilli,Albert Schömig,Adnan Kastrati +6 more
TL;DR: Based on the genetic analysis in a high-risk population of acute MI patients with interventional treatment and continuous clopidogrel therapy, a protective effect for carriers of an increased-function CYP2C19*17 T-allele with significantly lower rates of TLR and MACE is found.
Journal ArticleDOI
Meta-analyses of the association between cytochrome CYP2C19 loss- and gain-of-function polymorphisms and cardiovascular outcomes in patients with coronary artery disease treated with clopidogrel
Michel Zabalza,Isaac Subirana,Joan Sala,Carla Lluis-Ganella,Gavin Lucas,Marta Tomás,Rafel Masiá,Jaume Marrugat,Ramon Brugada,Roberto Elosua +9 more
TL;DR: The results question the relevance of the CYP2C19 loss-of-function alleles in the prediction of major cardiovascular events beyond stent thrombosis in coronary patients treated with clopidogrel.
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