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
Cytochrome P450 genetic polymorphisms and the response to prasugrel: relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes.
Jessica L. Mega,Sandra L Close,Stephen D. Wiviott,Lei Shen,Richard D. Hockett,John T. Brandt,Joseph R. Walker,Elliott M. Antman,William L. Macias,Eugene Braunwald,Marc S. Sabatine +10 more
TL;DR: Common functional CYP genetic variants do not affect active drug metabolite levels, inhibition of platelet aggregation, or clinical cardiovascular event rates in persons treated with prasugrel, and these pharmacogenetic findings are in contrast to observations with clopidogrel.
Journal ArticleDOI
Genetic variants in ABCB1 and CYP2C19 and cardiovascular outcomes after treatment with clopidogrel and prasugrel in the TRITON–TIMI 38 trial: a pharmacogenetic analysis
Jessica L. Mega,Sandra L Close,Sandra L Close,Stephen D. Wiviott,Lei Shen,Joseph R. Walker,Tabassome Simon,Elliott M. Antman,Eugene Braunwald,Marc S. Sabatine +9 more
TL;DR: Individuals with the ABCB1 3435C→T genotype have reduced platelet inhibition and are at increased risk of recurrent ischaemic events during clopidogrel treatment, and in patients with acute coronary syndromes who have undergone percutaneous intervention, this polymorphism is significantly associated with the risk of cardiovascular death, myocardial infarction, or stroke.
Journal ArticleDOI
Cytochrome 2C19*17 Allelic Variant, Platelet Aggregation, Bleeding Events, and Stent Thrombosis in Clopidogrel-Treated Patients With Coronary Stent Placement
Dirk Sibbing,Werner Koch,Daniela Gebhard,Tibor Schuster,Siegmund Braun,Julia Stegherr,Tanja Morath,Albert Schömig,Nicolas von Beckerath,Adnan Kastrati +9 more
TL;DR: CYP2C19*17 carrier status is significantly associated with enhanced response to clopidogrel and an increased risk of bleeding andMultivariate analysis confirmed the independent association of CYP2C 19*17 allele carriage with platelet aggregation values and the occurrence of bleeding.
Journal ArticleDOI
Clines, clusters, and the effect of study design on the inference of human population structure.
Noah A. Rosenberg,Saurabh Mahajan,Sohini Ramachandran,Chengfeng Zhao,Jonathan K. Pritchard,Marcus W. Feldman +5 more
TL;DR: Analysis of the 993-locus dataset corroborates earlier results: if enough markers are used with a sufficiently large worldwide sample, individuals can be partitioned into genetic clusters that match major geographic subdivisions of the globe, with some individuals from intermediate geographic locations having mixed membership in the clusters that correspond to neighboring regions.
Journal ArticleDOI
Cytochrome P450 2C19 681G>A Polymorphism and High On-Clopidogrel Platelet Reactivity Associated With Adverse 1-Year Clinical Outcome of Elective Percutaneous Coronary Intervention With Drug-Eluting or Bare-Metal Stents
Dietmar Trenk,Willibald Hochholzer,Martin F. Fromm,Ligia-Emilia Chialda,Andreas Pahl,Christian M. Valina,Christian Stratz,Peter Schmiebusch,Hans-Peter Bestehorn,Heinz Joachim Büttner,Franz-Josef Neumann +10 more
TL;DR: Patients carrying at least one CYP2C19*2 allele are more prone to high-on clopidogrel platelet reactivity, which is associated with poor clinical outcome after coronary stent placement, and the effect of ClopidOGrel Loading and Risk of PCI is investigated.
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Jessica L. Mega,Tabassome Simon,Jean-Philippe Collet,Jeffrey L. Anderson,Elliott M. Antman,Kevin P. Bliden,Christopher P. Cannon,Nicolas Danchin,Betti Giusti,Paul A. Gurbel,Benjamin D. Horne,Jean Sebastian Hulot,Adnan Kastrati,Gilles Montalescot,Franz-Josef Neumann,Lei Shen,Dirk Sibbing,P. Gabriel Steg,Dietmar Trenk,Stephen D. Wiviott,Marc S. Sabatine +20 more