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Observational Study
. 2015 Feb;15(1):20-5.
doi: 10.1038/tpj.2014.28. Epub 2014 Jul 8.

Clinical outcomes associated with proton pump inhibitor use among clopidogrel-treated patients within CYP2C19 genotype groups following acute myocardial infarction

J P Depta  1 , P A Lenzini  2 , D E Lanfear  3 , T Y Wang  4 , J A Spertus  5 , R G Bach  1 , S Cresci  6
Affiliations
Observational Study

Clinical outcomes associated with proton pump inhibitor use among clopidogrel-treated patients within CYP2C19 genotype groups following acute myocardial infarction

J P Depta et al. Pharmacogenomics J. 2015 Feb.

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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Conflict of interest statement

Conflicts of Interest: Jeremiah P. Depta: None

Petra A. Lenzini: None

David E. Lanfear: None

Tracy Y. Wang: Research Grants: Lilly USA (Significant), Daiichi Sankyo (Significant), and Gilead Science (Significant); Consultant: Astra Zeneca (Modest), American College of Cardiology Foundation (Significant)

John A. Spertus: Research Grants: Eli Lilly, EveHeart, Genentech, Gilead; Consultant: St. Jude Medical (modest), United Healthcare (modest), Amgen (modest), Gilead (modest), Genentech (modest), Janssen (modest), Novartis (modest); Copyrights/Patents: Seattle Angina Questionnaire, Kansas City Cardiomyopathy Questionnaire, Peripheral Artery Questionnaire, US Patents: 7,643,969; 7,853,456; 12/965,656; 13/615,401

Richard G. Bach: Research Grants: AstraZeneca, Eli Lilly, Bristol-Myers Squibb, Merck/Schering-Plough; Consultant (CEC Activity only): Roche (Significant), Pfizer (Modest)

Sharon Cresci: None

Figures

Figure 1
Figure 1
Kaplan-Maier analysis of cardiac rehospitalization associated with and without the use of a proton pump inhibitors (PPI) in Caucasian clopidogrel-treated genotyped TRIUMPH patients following an acute myocardial infarction. Freedom from cardiac rehospitalization are compared between PPI users and non-users within (A) all genotyped Caucasians, (B) CYP2C19*1 homozygotes, (C) carriers of the CYP2C19*2 allele, and (D) carriers of the CYP2C19*17 allele. In Caucasians, PPI use was associated with significantly increased rates of cardiac rehospitalization (A) and was most significant among Caucasian carriers of the gain of function CYP2C19*17 allele (D).
Figure 1
Figure 1
Kaplan-Maier analysis of cardiac rehospitalization associated with and without the use of a proton pump inhibitors (PPI) in Caucasian clopidogrel-treated genotyped TRIUMPH patients following an acute myocardial infarction. Freedom from cardiac rehospitalization are compared between PPI users and non-users within (A) all genotyped Caucasians, (B) CYP2C19*1 homozygotes, (C) carriers of the CYP2C19*2 allele, and (D) carriers of the CYP2C19*17 allele. In Caucasians, PPI use was associated with significantly increased rates of cardiac rehospitalization (A) and was most significant among Caucasian carriers of the gain of function CYP2C19*17 allele (D).
Figure 1
Figure 1
Kaplan-Maier analysis of cardiac rehospitalization associated with and without the use of a proton pump inhibitors (PPI) in Caucasian clopidogrel-treated genotyped TRIUMPH patients following an acute myocardial infarction. Freedom from cardiac rehospitalization are compared between PPI users and non-users within (A) all genotyped Caucasians, (B) CYP2C19*1 homozygotes, (C) carriers of the CYP2C19*2 allele, and (D) carriers of the CYP2C19*17 allele. In Caucasians, PPI use was associated with significantly increased rates of cardiac rehospitalization (A) and was most significant among Caucasian carriers of the gain of function CYP2C19*17 allele (D).
Figure 1
Figure 1
Kaplan-Maier analysis of cardiac rehospitalization associated with and without the use of a proton pump inhibitors (PPI) in Caucasian clopidogrel-treated genotyped TRIUMPH patients following an acute myocardial infarction. Freedom from cardiac rehospitalization are compared between PPI users and non-users within (A) all genotyped Caucasians, (B) CYP2C19*1 homozygotes, (C) carriers of the CYP2C19*2 allele, and (D) carriers of the CYP2C19*17 allele. In Caucasians, PPI use was associated with significantly increased rates of cardiac rehospitalization (A) and was most significant among Caucasian carriers of the gain of function CYP2C19*17 allele (D).
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