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Comparison of O..

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It is conservatively estimated that 733,000 to 1,365,000 patients were discharged with acute coronary syndromes (ACS) from hospitals in 2006.1 These patients are often started on clopidogrel to reduce the risk of recurrent cardiovascular events and may also be given a proton pump inhibitor (PPI) if at risk for gastrointestinal bleeding. Clopidogrel is a prodrug that must be activated in the liver by what is believed to be CYP2C19. It has been recently reported that PPIs decrease the antiplatelet effect of clopidogrel, possibly due to inhibition of CYP2C19 enzyme.2 Different PPIs are metabolized by CYP2C19 to a varying degree.3

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Cuisset and colleagues recently published the results of a prospective randomized study that compared the influence of omeprazole and pantoprazole on high dose clopidogrel in patients with non-ST-segment elevation (NSTE) ACS that had undergone successful coronary stenting.4 Individuals with new findings of ST-segment changes in >2 leads, coronary artery disease (indicated by revascularization or myocardial infarction), or elevated levels of biochemical marker in addition to clinical symptoms compatible with acute myocardial ischemia <12 hours before admission were considered to have NSTE ACS. The primary end point of the study was clopidogrel response 1 month after hospital discharge assessed by platelet reactivity index vasoactive stimulated phosphoprotein (PRI VASP). PRI VASP is an index for platelet reactivity to clopidogrel where higher values indicate thrombosis is more likely to occur. The secondary end point was post-treatment platelet reactivity assessed with adenosine diphosphate-induced aggregation for platelet reactivity (ADP-Ag). ADP-Ag is determined by comparing the difference in percentage of light transmitted through the sample vs. a control with very few platelets.

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All 104 patients were given oral loading doses of 250-mg aspirin and 600-mg clopidogrel at least 12 hours before stenting and then discharged with 75-mg aspirin and 150-mg clopidogrel daily. In addition, patients were randomized to receive either omeprazole 20-mg or pantoprazole 20-mg. Platelet parameters were assessed 12 to 24 hours after the loading dose and again 1 month after hospital discharge. 

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The omeprazole group had an insignificant difference in the percentage of males (47% vs. 43%, p=0.25) and age of patients (64.5 vs. 62.5, p=0.34) when compared to the pantoprazole group. The baseline characteristics of both groups were similar, particularly PRI VASP and ADP-Ag. However, the omeprazole group had more patients with hypertension when compared to the pantoprazole group (34 patients vs. 22 patients, p=0.02). Review of platelet responsiveness by PRI VASP revealed that patients on pantoprazole had a significantly better platelet response to clopidogrel than did patients on omeprazole (36 + 20% versus 48 + 17%, respectively (p=0.007)). There were more clopidogrel nonresponders, defined as a PRI VASP >50%, identified in the omeprazole group than in the pantoprazole group (44% vs. 23%, p=0.04, odds ratio 2.6, 95% confidence interval 1.2 to 6.2). The secondary end point did not show a significant difference for platelet reactivity with ADP-Ag between the 2 groups (52 + 15% and 50 + 18%, respectively (p=0.29)).

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To summarize, even with high doses of clopidogrel, platelet responsiveness was decreased more in patients taking omeprazole than in patients taking pantoprazole suggesting that pantoprazole should be preferred over omeprazole in patients also receiving clopidogrel. This study was limited by the small sample size. Finally, although platelet responsiveness was affected based on PRI VASP, this study did not evaluate any patient-related clinical outcomes, such as recurrent myocardial infarction or death. Randomized controlled trials assessing clinical outcomes would be beneficial to confirm the effects seen in this study.

1. Lloyd-Jones D, Adams R, Carnethon M, et al. ...

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