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Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C19 Genotype and Clopidogrel Therapy: 2013 Update

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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).

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Population pharmacogenomics: an update on ethnogeographic differences and opportunities for precision public health

TL;DR: In this paper, the authors provide an extensive updated analysis of population pharmacogenomics in ten pharmacokinetic genes (CYP2D6, CYP2C19, DPYD, TPMT, NUDT15 and SLC22A1), drug targets (CFTR) and genes involved in drug hypersensitivity (HLA-A, HLA-B) or drug-induced acute hemolytic anemia (G6PD).
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Proton pump inhibitors and other disease-based factors in the recurrence of adverse cardiovascular events following percutaneous coronary angiography: A long-term cohort

TL;DR: It is concluded that pharmacokinetic interaction between PPIs and antiplatelet therapy is not associated with adverse CV events and a comprehensive, multicenter, open-label trial including all PPI subclasses and patient and disease-based factors is warranted for a fair evaluation.
Journal ArticleDOI

The ABCB1, CYP2C19, CYP3A5 and CYP4F2 genetic polymorphisms and platelet reactivity in the early phases of acute coronary syndromes.

TL;DR: The reactivity of the on-clopidogrel platelet in the early phase of ACS is influenced primarily by the CYP2C19 polymorphisms, and the findings of the present study could supply additional evidence regarding the clinical appropriateness of the CYC19 genetic testing for designing suitable antiplatelet therapy in theEarly phase ofACS.
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Switching from prasugrel to clopidogrel based on Cytochrome P450 2C19 genotyping in East Asian patients stabilized after acute myocardial infarction.

TL;DR: Individualized antiplatelet regimens based on CYP2C19 genotyping may improve likelihood of achieving a TW of OPR compared to fixed dose of prasugrel 10 mg during maintenance periods of AMI in East Asians.
References
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Journal ArticleDOI

Meta-Analysis: A Constantly Evolving Research Integration Tool

TL;DR: The four articles in this special section onMeta-analysis illustrate some of the complexities entailed in meta-analysis methods and contributes both to advancing this methodology and to the increasing complexities that can befuddle researchers.
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Prasugrel versus Clopidogrel in Patients with Acute Coronary Syndromes

TL;DR: In patients with acute coronary syndromes with scheduled percutaneous coronary intervention, prasugrel therapy was associated with significantly reduced rates of ischemic events, including stent thrombosis, but with an increased risk of major bleeding, including fatal bleeding.
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Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes

TL;DR: In patients who have an acute coronary syndrome with or without ST-segment elevation, treatment with ticagrelor as compared with clopidogrel significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke without an increase in the rates of overall major bleeding but with an increase of non-procedure-related bleeding.

A Systematic Review and Meta-analysis

TL;DR: A systematic review of studies published from January 1, 1950, through November 31, 2008 using PubMed, EMBASE, Web of Knowledge, CINAHL, and all Evidence-Based Medicine Reviews found that randomized clinical trials and prospective studies of RRTs that reported data on changes in the primary outcome of hospital mortality or the secondary outcome of cardiopulmonary arrest cases were included.
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Genetic Structure of Human Populations

TL;DR: General agreement of genetic and predefined populations suggests that self-reported ancestry can facilitate assessments of epidemiological risks but does not obviate the need to use genetic information in genetic association studies.
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