Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study.
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.
Gilard
Martine
M
Department of Cardiology, Brest University Hospital, Brest, France. martine.gilard@chu-brest.fr
Arnaud
Bertrand
B
Cornily
Jean-Christophe
JC
Le Gal
Grégoire
G
Lacut
Karine
K
Le Calvez
Geneviève
G
Mansourati
Jacques
J
Mottier
Dominique
D
Abgrall
Jean-François
JF
Boschat
Jacques
J
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
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