Key result
Omeprazole decreases the antiplatelet effect of clopidogrel, driving ~29% higher platelet reactivity versus placebo.
Why the study?
In an observational study, clopidogrel activity on platelets was diminished in patients receiving proton pump inhibitors, prompting evaluation of the influence of omeprazole on clopidogrel efficacy.
RCT (n=124)
Double-blind
randomized
Answers are grounded in this paper and cite their sources.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The data on which the FDA warning was based came mostly from laboratory assays of platelet function. Preliminary results from a randomized, controlled clinical trial with hard end points show that, for the time being, we should not change the way we manage patients.”
“Although we should not take such warnings lightly, we also should not be alarmed. The data on which the FDA warning was based came mostly from laboratory assays of platelet function.”
Randomized double-blind trial demonstrates omeprazole significantly blunts clopidogrel antiplatelet response in stented cardiac patients, indicating a critical drug interaction.
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.
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Gilard et al. (2008) conducted an RCT in Coronary artery stent implantation (n=124). Omeprazole vs. Placebo was evaluated on Platelet reactivity index (PRI) value at the 7-day treatment period (p=< 0.0001). Omeprazole significantly decreased the antiplatelet effect of clopidogrel, resulting in a higher mean platelet reactivity index at 7 days compared to placebo (51.4% vs 39.8%; p < 0.0001).
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