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CLINICAL RESEARCH: ANTIPLATELET THERAPY

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

Thomas Cuisset, MD^_*,,,_*, Corinne Frere, MD^,, Jacques Quilici, MD^_*, Raphael Poyet, MD^_*, Bénédicte Gaborit, MD^,, Laurent Bali, MD^_*, Olivier Brissy, MD^_*, Pierre-Emmanuel Morange, MD, PhD^,, Marie-Christine Alessi, MD, PhD^, and Jean-Louis Bonnet, MD^_*

^_* Département de Cardiologie, CHU Timone, Marseille, France
Laboratoire d'Hématologie, CHU Timone, Marseille, France
INSERM, UMR 626, Faculté de Médecine, Marseille, France

Manuscript received March 3, 2009; revised manuscript received April 28, 2009, accepted May 4, 2009.

^_* Reprint requests and correspondence: Dr. Thomas Cuisset, CHU Timone, Cardiology, 264 rue Saint Pierre, Marseille, France 13385 (Email: thomascuisset{at}voila.fr).

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.

Key Words: proton pump inhibitors • clopidogrel response • VASP assay • cytochrome P450 • coronary stenting

Abbreviations and Acronyms   ADP = adenosine diphosphate   ADP-Ag = adenosine diphosphate-induced aggregation for platelet reactivity   MFI = median fluorescence intensity   NSTE ACS = non–ST-segment elevation acute coronary syndrome   PPI = proton pump inhibitor   PRI = platelet reactivity index   VASP = vasoactive stimulated phosphoprotein

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