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 ArticleDOI
Genetic polymorphisms of CYP2C19 influences the response to clopidogrel in ischemic heart disease patients in the South Indian Tamilian population.
K. Subraja,Steven Aibor Dkhar,Rajendran Priyadharsini,Byrappa Kempalalakshmamma Ravindra,Deepak Gopal Shewade,Santhosh Satheesh,Magadi Gopalakrishna Sridhar,Sunil K Narayan,Chandrasekaran Adithan +8 more
TL;DR: Patients with CYP2C19 (*2 or *3) genetic polymorphisms had higher residual platelet activities and were associated with a reduced antiplatelet response to clopidogrel, and these findings mandate further studies aimed at initiating genome-based personalized antiplatelets therapy.
Journal ArticleDOI
Relation of CYP2C19 loss-of-function polymorphism to the occurrence of stent thrombosis.
TL;DR: A review of the principal studies contributing to establish the relationship between CYP2C19*2 polymorphism and adverse outcomes in high risk patients on clopidogrel treatment concludes that prospective studies are urgently needed to determine the clinical impact of a score that takes into account individual characteristics of patients.
Journal ArticleDOI
Cytochrome P450 2C19 Polymorphism, Suboptimal Reperfusion and All-Cause Mortality in Patients with Acute Myocardial Infarction
Łukasz A. Małek,Jakub Przyłuski,Mateusz Śpiewak,Mariusz Kłopotowski,Grażyna Kostrzewa,Mariusz Kruk,Rafał Płoski,Adam Witkowski,Witold Rużyłło +8 more
TL;DR: The CYP2C19*2 allele is an independent predictor of suboptimal reperfusion in patients with AMI undergoing PCI with stenting after pretreatment with clopidogrel and may increase the risk of all-cause mortality.
Journal ArticleDOI
CYP2C19*2/ABCB1-C3435T polymorphism and risk of cardiovascular events in coronary artery disease patients on clopidogrel: Is clinical testing helpful?
Mukesh Singh,Tejaskumar Shah,Sasikanth Adigopula,Janos Molnar,Aziz Ahmed,Sandeep Khosla,Rohit Arora +6 more
TL;DR: In CAD patients on clopidogrel therapy, CYP2C19*2 polymorphism is associated with significantly increased adverse cardiovascular events, however, due to the low positive predictive value, routine genetic testing cannot be recommended at present.
Journal ArticleDOI
High on-treatment platelet reactivity by ADP and increased risk of MACE in good clopidogrel metabolizers
Rossella Marcucci,Betti Giusti,Rita Paniccia,Anna Maria Gori,Claudia Saracini,Serafina Valente,Cristina Giglioli,Guido Parodi,David Antoniucci,Gian Franco Gensini,Rosanna Abbate +10 more
TL;DR: Both phenotype and genotype are clinically relevant for the evaluation of the antiplatelet effect of clopidogrel and for the prognostic stratification of ACS patients.
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