Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study

J Am Coll Cardiol. 2008 Jan 22;51(3):256-60. doi: 10.1016/j.jacc.2007.06.064.


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.

Trial registration: NCT00349661.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Angioplasty, Balloon, Coronary
  • Cell Adhesion Molecules / metabolism
  • Clopidogrel
  • Double-Blind Method
  • Drug Antagonism
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Microfilament Proteins / metabolism
  • Middle Aged
  • Myocardial Infarction / therapy
  • Omeprazole / pharmacology*
  • Omeprazole / therapeutic use
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Prospective Studies
  • Proton Pump Inhibitors / pharmacology*
  • Proton Pump Inhibitors / therapeutic use
  • Stents
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / antagonists & inhibitors
  • Ticlopidine / therapeutic use


  • Cell Adhesion Molecules
  • Microfilament Proteins
  • Phosphoproteins
  • Platelet Aggregation Inhibitors
  • Proton Pump Inhibitors
  • vasodilator-stimulated phosphoprotein
  • Clopidogrel
  • Omeprazole
  • Ticlopidine

Associated data