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

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.

Appropriate Prescribing and Important Drug Interactions in Older Adults

“…29,30 One possible explanation for the lack of poor outcomes related to this interaction is that CYP2C19 genotype groups have different risk for clinically important susceptibility to this drug interaction. 31 Given this uncertainty, the Food and Drug Administration (FDA) has recently recommended labeling changes that the PPIs omeprazole and esomeprazole should be avoided in patients taking clopidogrel. 32 Elderly patients are at much higher risk for osteoporosis than the younger population.…”

A novel genetic marker of decreased inflammation and improved survival after acute myocardial infarction

“…TRIUMPH follow-up and outcome ascertainment and adjudication have previously been described. [2, 9, 12]…”

SurvivalGWAS_Power: a user friendly tool for power calculations in pharmacogenetic studies with “time to event” outcomes

“…The varied collection of design scenarios includes adding a recruitment period, SNP-treatment interactions, and/or different censoring options (for example, withdrawal due to an adverse treatment event). We created these pharmacogenomic study designs after a thorough examination of published studies in the literature [5], including Charland et al [6], Depta et al [7], Wiese et al [8], and Absenger et al [9]. The power calculation is performed by simulating multiple datasets based on the user specified parameter settings and study design options, specifically testing for SNP associations (and SNP-treatment interactions, if required) with the time to event outcome across all simulated datasets.…”