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

J Am Coll Cardiol. 2009 Sep 22;54(13):1149-53. doi: 10.1016/j.jacc.2009.05.050.

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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles / pharmacology*
  • Acute Coronary Syndrome / therapy*
  • Aged
  • Angioplasty, Balloon, Coronary
  • Anti-Ulcer Agents / pharmacology
  • Clopidogrel
  • Drug Interactions
  • Female
  • Humans
  • Male
  • Middle Aged
  • Omeprazole / pharmacology*
  • Pantoprazole
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Prospective Studies
  • Proton Pump Inhibitors / pharmacology*
  • Stents
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*

Substances

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Anti-Ulcer Agents
  • Platelet Aggregation Inhibitors
  • Proton Pump Inhibitors
  • Clopidogrel
  • Pantoprazole
  • Omeprazole
  • Ticlopidine