Comparison of omeprazole and pantoprazole influence on a high 150-mg clopidogrel maintenance dose the PACA (Proton Pump Inhibitors And Clopidogrel Association) prospective randomized study.

ABSTRACT

OBJECTIVES: This study sought to compare the effect of 2 proton pump inhibitors (PPIs) on platelet response to clopidogrel after coronary stenting for non-ST-segment elevation acute coronary syndrome (NSTE ACS). BACKGROUND: Use of omeprazole has been reported to significantly decrease the clopidogrel antiplatelet effect because of cytochrome P450 interaction. Because all PPIs are metabolized by CYP2C19, but to a varying degree, we hypothesized that the reported negative omeprazole-clopidogrel drug interaction may not be caused by a class effect. METHODS: A total of 104 patients undergoing coronary stenting for NSTE ACS were prospectively included and randomized to omeprazole or pantoprazole 20 mg. They received at discharge 75-mg aspirin and 150-mg clopidogrel. Platelet reactivity index (PRI) vasoactive stimulated phosphoprotein (VASP) was used to assess clopidogrel response and adenosine diphosphate (ADP)-induced aggregation for platelet reactivity (ADP-Ag). RESULTS: After 1 month, patients receiving pantoprazole had a significantly better platelet response to clopidogrel as assessed with the PRI VASP 36 +/- 20% versus 48 +/- 17% (p = 0.007). We identified more clopidogrel nonresponders in the omeprazole group than in the pantoprazole group 44% versus 23% (p = 0.04), odds ratio 2.6 (95% confidence interval 1.2 to 6.2). Conversely, we did not observe any significant difference in platelet reactivity with ADP-Ag between the omeprazole and pantoprazole groups 52 +/- 15% and 50 +/- 18%, respectively (p = 0.29). CONCLUSIONS: The present findings suggest the preferential use of pantoprazole compared with omeprazole in patients receiving clopidogrel to avoid any potential negative interaction with CYP2C19.