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    Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention

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    Author
    Cavallari, L.H.
    Lee, C.R.
    Beitelshees, A.L.
    Date
    2018
    Journal
    JACC: Cardiovascular Interventions
    Publisher
    Elsevier Inc.
    Type
    Article
    
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    Show full item record
    See at
    https://dx.doi.org/10.1016/j.jcin.2017.07.022
    Abstract
    Objectives This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI). Background CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI. Methods After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights. Results Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60). Conclusions These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value. Copyright 2018 American College of Cardiology Foundation
    Keyword
    antiplatelet therapy
    cardiovascular events
    clopidogrel
    CYP2C19
    percutaneous coronary intervention
    pharmacogenomics
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85032917144&doi=10.1016%2fj.jcin.2017.07.022&partnerID=40&md5=610776702753abae2a15e088bc42effe; http://hdl.handle.net/10713/9788
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.jcin.2017.07.022
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    UMB Open Access Articles 2018

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