Abstract
We examined clinical outcomes with proton pump inhibitors (PPI) use within CYP2C19 genotype groups during clopidogrel treatment following acute myocardial infarction (AMI). 2062 patients were genotyped for CYP2C19*2 and *17 variants in TRIUMPH. 12 month clinical outcomes were analyzed among patients discharged on clopidogrel within CYP2C19*2 carrier, CYP2C19*17 carrier, and CYP2C19*1 homozygote genotype groups. PPI use was not associated with a difference in mortality. Among clopidogrel-treated Caucasians following AMI, PPI use was associated with a significantly higher rate of cardiac rehospitalization (HR 1.62, 95% CI 1.19–2.19; P=0.002) compared with no PPI use. PPI users who were carriers of the CYP2C19*17 variant experienced significantly higher rates of cardiac rehospitalization (HR 2.05, 95% CI 1.26–3.33; P=0.003), carriers of the CYP2C19*2 variant had a trend toward increased 1-year cardiac rehospitalization (HR 1.69, 95% CI 0.95–2.99; P=0.07), while no significant differences were observed among CYP2C19*1 homozygotes. These results indicate that the risks associated with PPI use among clopidogrel-treated Caucasian post-MI patients are impacted by CYP2C19 genotype, and suggest knowledge of genotype may be useful for personalizing PPI use among patients following AMI to reduce rehospitalization.
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Acknowledgements
This work and S. Cresci’s effort are supported in part by the National Institutes of Health (Cresci R01 NR013396). TRIUMPH was sponsored by the National Institutes of Health: Washington University School of Medicine SCCOR Grant P50 HL077113.
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TY Wang has received research grants from Lilly USA (significant), Daiichi Sankyo (significant) and Gilead Science (significant), and is a consultant to Astra Zeneca (modest), American College of Cardiology Foundation (significant). JA Spertus has received research grants from Eli Lilly, EveHeart, Genentech and Gilead, and is a consultant to St Jude Medical (modest), United Healthcare (modest), Amgen (modest), Gilead (modest), Genentech (modest), Janssen (modest) and Novartis (modest). Copyrights/Patents apply to Seattle Angina Questionnaire, Kansas City Cardiomyopathy Questionnaire and Peripheral Artery Questionnaire. US Patents: 7,643,969; 7,853,456; 12/965,656; and 13/615,401. RG Bach has received research grants from AstraZeneca, Eli Lilly, Bristol-Myers Squibb and Merck/Schering-Plough, and is a consultant (CEC activity only) to Roche (significant), Pfizer (modest). The remaining authors declare no conflict of interest.
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Depta, J., Lenzini, P., Lanfear, D. et al. Clinical outcomes associated with proton pump inhibitor use among clopidogrel-treated patients within CYP2C19 genotype groups following acute myocardial infarction. Pharmacogenomics J 15, 20–25 (2015). https://doi.org/10.1038/tpj.2014.28
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DOI: https://doi.org/10.1038/tpj.2014.28
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