Omeprazole CLopidogrel Aspirin - OCLA


The goal of this trial was to evaluate the influence of proton pump inhibitors, specifically omeprazole, on the antiplatelet efficacy of clopidogrel.


The antiplatelet action of clopidogrel would be reduced in patients receiving associated omeprazole treatment.

Study Design

Study Design:

Patients Screened: 354
Patients Enrolled: 140
NYHA Class: N/A
Mean Follow Up: 7 days
Mean Patient Age: 63.0 years (mean)
Female: 22
Mean Ejection Fraction: N/A

Patient Populations:

Patients with coronary atherosclerosis who were undergoing elective coronary stent implantation, and those who provided informed consent


Previous treatment with clopidogrel or a proton pump inhibitor, history of thrombocytopenia (<150,000 platelets/ml), bleeding diatheses, liver disease, gastrointestinal ulcer, or pregnancy

Primary Endpoints:

Mean PRI, as measured by VASP phosphorylation at day 7

Secondary Endpoints:

• Mean PRI decrease at day 7, compared with day 1
• Percent of patients with PRI <50% (good responders), compared with PRI >50% (bad responders)

Drug/Procedures Used:

Patients undergoing elective coronary stent implantation, receiving aspirin 75 mg/day, and receiving clopidogrel (loading dose 300 mg, followed by maintenance dose 75 mg/day) were randomly assigned to 20 mg/day omeprazole or placebo, for 7 days.

Concomitant Medications:

Beta-blockers (87%), angiotensin-converting enzyme inhibitors (49%), and statins (94%)

Principal Findings:

A total of 140 patients were randomized: 70 to the omeprazole group and 70 to the placebo group. However, 16 patients were excluded from the analyses for various reasons, resulting in 64 patients in the omeprazole group and 60 patients in the placebo group. The baseline characteristics between the two groups were similar. The mean age of the patient population was 63 years, with 14% diabetics, and 9.7% with a prior history of myocardial infarction.

The primary outcome measure was mean platelet reactivity index (PRI), as measured by vasodilator stimulated phosphoprotein (VASP) phosphorylation. This correlates inversely with clopidogrel treatment efficacy—a higher PRI is associated with lower antiplatelet efficacy. On day 1, the mean PRI was similar between the two groups. In patients who received omeprazole in addition to aspirin and clopidogrel, the mean PRI at day 7 was 51.4 ± 16.4%, compared with 39.8 ± 15.4% in those who received aspirin and clopidogrel alone (p < 0.0001). The mean PRI decrease at day 7 was 32.6% in the omeprazole group, compared with 43.3% in the placebo group (p < 0.0001). Also, 39 (60.9%) patients were poor responders (PRI <50%) in the omeprazole group, compared with 16 (26.7%) in the placebo group (p < 0.0001), at day 7.

There was one episode of stent thrombosis in each arm. There were no deaths.


The results of this small but intriguing study suggest that concomitant use of inhibitors of cytochrome P-450 (CYP) (specifically, CYP2C19) such as proton-pump inhibitors may decrease the antiplatelet efficacy of clopidogrel, which is metabolized to its active form by the same enzyme complex. Clinically, this is important, since the decrease in antiplatelet efficacy may be associated with an increased risk of stent thrombosis. Unwarranted use of proton pump inhibitors should therefore be discouraged.

The following points should be noted before the findings of this study can be considered generalizable:

1. The conversion of clopidogrel to its active metabolite is dependent on several CYP isoforms. Many studies have suggested that CYP3A4 may be the major contributor in this complex biochemical reaction. In fact, a similar concern had been raised regarding a potential negative interaction between clopidogrel and statins, especially atorvastatin, which competes with clopidogrel for CYP3A4. However, this was not borne out in large clinical trials (see Saw et al., J Am Coll Cardiol 2007;50:291-5).

2. Another issue arises from the use of surrogate endpoints. To date, no large studies have unequivocally demonstrated that superior (or inferior) inhibition of platelet aggregation is associated with better (or worse) outcomes. Currently held associations are based on small clinical studies. Whether the observed increase in platelet reactivity would be directly associated with worse outcomes, such as stent thrombosis, is yet unclear.


Gilard M, Arnaud B, Cornily JC, et al. 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;51:256-60.

Clinical Topics: Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Novel Agents, Statins, Interventions and Coronary Artery Disease

Keywords: Outcome Assessment (Health Care), Coronary Artery Disease, Myocardial Infarction, Platelet Aggregation Inhibitors, Protein Isoforms, Cytochromes, Ticlopidine, Blood Platelets, Heptanoic Acids, Proton Pump Inhibitors, Vasodilator Agents, Stents, Treatment Outcome, Pyrroles, Biological Markers, Thrombosis, Phosphoproteins, Omeprazole, Informed Consent, Phosphorylation, Diabetes Mellitus

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