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

• Published in: Journal of the American College of Cardiology Vol. 51; no. 3; pp. 256 - 260
• Main Authors: Gilard, Martine, Arnaud, Bertrand, Cornily, Jean-Christophe, Le Gal, Grégoire, Lacut, Karine, Le Calvez, Geneviève, Mansourati, Jacques, Mottier, Dominique, Abgrall, Jean-François, Boschat, Jacques
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 22.01.2008
• Subjects: Cardiovascular; Internal Medicine; VASP; PPI; MFI; SD; ADP; PRI; mean fluorescence intensity; platelet reactivity index; adenosine diphosphate; vasodilator-stimulated phosphoprotein; proton pump inhibitor; standard deviation
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2007.06.064

Influence of Omeprazole on the Antiplatelet Action of Clopidogrel Associated With Aspirin: The Randomized, Double-Blind OCLA (Omeprazole CLopidogrel Aspirin) Study Martine Gilard, Bertrand Arnaud, Jean-Christophe Cornily, Grégoire Le Gal, Karine Lacut, Geneviève Le Calvez, Jacques Mansourati, Dominique Mottier, Jean-François Abgrall, Jacques Boschat In a previous observational study, we found the effect of clopidogrel as tested by vasodilator-stimulated phosphoprotein (VASP) phosphorylation to be diminished in patients receiving proton pump inhibitor treatment. In this double-blind placebo-controlled trial, 124 consecutive patients were randomized to receive either associated omeprazole (20 mg/day) or placebo for 7 days. The clopidogrel effect was tested on Day 1 and Day 7 in both groups by measuring platelet phosphorylated VASP. Our main end point was to compare platelet activation in the 2 groups. Omeprazole significantly decreased the antiplatelet effect of clopidogrel as assessed by a VASP phosphorylation test (p < 0.0001). This trial sought to assess the influence of omeprazole on clopidogrel efficacy. 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. 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. 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). 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)