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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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Incidence, preventability, and causality of adverse drug reactions at a university hospital emergency department.

TL;DR: The same ATC classes, antithrombotics and cytostatics, were involved in ADRs causing university clinic hospitalizations as those identified previously in drug-related hospital fatalities.
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EHR based Genetic Testing Knowledge Base (iGTKB) Development.

TL;DR: An EHR based genetic testing knowledge base, iGTKB, which is to be integrated into the Genetic Testing Ontology (GTO) by providing relevant clinical evidence, and ultimately to support development of genetic testing recommendation system, iGenetics.
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Urine metabolic ratio of omeprazole in relation to CYP2C19 polymorphisms in Russian peptic ulcer patients.

TL;DR: A connection between particular CYP2C19 genotypes and urine metabolic ratio of omeprazole in Russian peptic ulcer patients is found and needs to be improved as in the modification it worked mainly for UMs and did not differentiate all patients according to omepazole biotransformation activity.
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East Asian perspective on the interaction between proton pump inhibitors and clopidogrel

TL;DR: For East Asian patients in particular, the clinical relevance of the interaction between PPIs and clopidogrel remains unclear because of conflicting data, as well as underrepresentation of East Asian subjects in landmark trials.
Posted ContentDOI

Towards a molecular systems model of coronary artery disease

TL;DR: This work reviews and highlights some of the main results in integrative approaches that consider multiple modalities simultaneously that have the potential to uncover the genetic basis of CAD, produce genomic risk scores (GRS) for disease prediction, disentangle the complex interactions underlying disease, and predict response to treatment.
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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