Influence of Omeprazole on the Antiplatelet Action of Clopidogrel Associated With Aspirin

Abstract

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.

Clopidogrel (Plavix)

“…12 However, the current position of the AHA is that there is no conclusive evidence that this translates to an increased risk of clinically significant thrombosis. 13 Strategies suggested to minimize PPI-induced inhibition include substituting the less inhibitory pantoprazole for omeprazole, 14 and spacing clopidogrel and PPI doses 12 hours apart from each other.…”

Clopidogrel and proton pump inhibitors: can near patient testing help in the tailoring of dual antiplatelet prescription?

“…Gilard et al [7] first highlighted the negative impact of PPIs and, in particular, omeprazole on the pharmacodynamic clopidogrel response, possibly owing to inhibition of CYP2C19, and this group further confirmed this drug-drug interaction by carrying out the randomized and double-blinded Omeprazole CLopidogrel Aspirin study [8]. Since then, however, other groups have shown that this response may not be relevant to all PPIs.…”

“…Previous studies assessing the pharmacodynamic effects of PPIs on clopidogrel activity have used vasodilator-stimulated phosphoprotein phosphorylation analysis or light-transmittance aggregometry [5,8,16]. To our knowledge, we are the first group to describe this response using the VerifyNow analyzer, a simple near patient device that can be used by clinicians who are not affiliated with academic research centers specializing in platelet function.…”

Chronic NSAIDs Therapy and Upper Gastrointestinal Tract – Mechanism of Injury, Mucosal Defense, Risk Factors for Complication Development and Clinical Management

“…This hypothesized impairment was additionally supported by the finding of genetic polymorphisms associated in CYP2C19 activity Singh et al 2010;Tiroch et al, 2010) and with a reduced antiplatelet activity and a worse clinical outcome (CV adverse events and re-infarction). Early clinical prospective studies in humans demonstrated a negative effect of omeprazole on surrogate clinical endpoints (ex vivo platelet assay, vasodilatator-stimulated phosphoprotein VASP) while other PPIs (pantoprazole and esomeprazole) did not (Gilard et al, 2008;Cuisset et al, 2009;O'Donoghue et al, 2009;Siller-Matula et al, 2009). …”