title: Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Cardiology, Brest University Hospital, Brest, France. martine.gilard@chu-brest.fr
authors.forename: Martine
authors.initials: M
authors.lastname: Gilard
authors.forename: Bertrand
authors.initials: B
authors.lastname: Arnaud
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Cornily
authors.forename: Grégoire
authors.initials: G
authors.lastname: Le Gal
authors.forename: Karine
authors.initials: K
authors.lastname: Lacut
authors.forename: Geneviève
authors.initials: G
authors.lastname: Le Calvez
authors.forename: Jacques
authors.initials: J
authors.lastname: Mansourati
authors.forename: Dominique
authors.initials: D
authors.lastname: Mottier
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Abgrall
authors.forename: Jacques
authors.initials: J
authors.lastname: Boschat
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D015815:Cell Adhesion Molecules / Q000378:metabolism; D000077144:Clopidogrel; D004311:Double-Blind Method; D004336:Drug Antagonism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D008875:Middle Aged; D009203:Myocardial Infarction / Q000628:therapy; D009853:Omeprazole / Q000494:pharmacology* / Q000627:therapeutic use; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015607:Stents; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000098662:Vasodilator-Stimulated Phosphoprotein; D000077144:Clopidogrel; D009853:Omeprazole; D013988:Ticlopidine