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J Am Coll Cardiol, 2008; 51:256-260, doi:10.1016/j.jacc.2007.06.064
© 2008 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: CLINICAL TRIAL

Influence of Omeprazole on the Antiplatelet Action of Clopidogrel Associated With Aspirin

The Randomized, Double-Blind OCLA (Omeprazole CLopidogrel Aspirin) Study

Martine Gilard, MD*,*, Bertrand Arnaud, PharmD{dagger}, Jean-Christophe Cornily, MD*, Grégoire Le Gal, MD§, Karine Lacut, MD{ddagger}, Geneviève Le Calvez, PharmD{dagger}, Jacques Mansourati, MD*, Dominique Mottier, MD§, Jean-François Abgrall, MD{dagger},1 and Jacques Boschat, MD*,1

* Department of Cardiology, Brest University Hospital, Brest, France
{dagger} Department of Hematology, INSERM 0502, Brest University Hospital, Brest, France
{ddagger} Center for Clinical Investigation, EA3878, Brest University Hospital, Brest, France
§ Department of Internal Medicine and Chest Diseases, Brest University Hospital, Brest, France.

Manuscript received March 19, 2007; revised manuscript received June 7, 2007, accepted June 12, 2007.

* Reprint requests and correspondence: Dr. Martine Gilard, Département de Cardiologie, CHU de la Cavale Blanche, Boulevard Tanguy Prigent, 29609 Brest Cédex, France. (Email: martine.gilard{at}chu-brest.fr).

Objectives: This trial sought to assess the influence of omeprazole on clopidogrel efficacy.

Background: Clopidogrel has proved its benefit in the treatment of atherothrombotic diseases. In a previous observational study, we found clopidogrel activity on platelets, tested by vasodilator-stimulated phosphoprotein (VASP) phosphorylation, to be diminished in patients receiving proton pump inhibitor (PPI) treatment.

Methods: In this double-blind placebo-controlled trial, all consecutive patients undergoing coronary artery stent implantation received aspirin (75 mg/day) and clopidogrel (loading dose, followed by 75 mg/day) and were randomized to receive either associated omeprazole (20 mg/day) or placebo for 7 days. Clopidogrel effect was tested on days 1 and 7 in both groups by measuring platelet phosphorylated-VASP expressed as a platelet reactivity index (PRI). Our main end point compared PRI value at the 7-day treatment period in the 2 groups.

Results: Data for 124 patients were analyzed. On day 1, mean PRI was 83.2% (standard deviation [SD] 5.6) and 83.9% (SD 4.6), respectively, in the placebo and omeprazole groups (p = NS), and on day 7, 39.8% (SD 15.4) and 51.4% (SD 16.4), respectively (p < 0.0001).

Results: Omeprazole significantly decreased clopidogrel inhibitory effect on platelet P2Y12 as assessed by VASP phosphorylation test. Aspirin-clopidogrel antiplatelet dual therapy is widely prescribed worldwide, with PPIs frequently associated to prevent gastrointestinal bleeding. The clinical impact of these results remains uncertain but merits further investigation. (OCLA: Influence of Omeprazole on the Antiplatelet Action of Clopidogrel Associated to Aspirin; http://www.clinicaltrials.gov/ct2/show/NCT00349661; NCT00349661 [ClinicalTrials.gov] )

Abbreviations and Acronyms
  ADP = adenosine diphosphate
  MFI = mean fluorescence intensity
  PPI = proton pump inhibitor
  PRI = platelet reactivity index
  SD = standard deviation
  VASP = vasodilator-stimulated phosphoprotein


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