Key result
Proton pump inhibitors may attenuate the antiplatelet activity of clopidogrel by competitively inhibiting cytochrome P450 enzymes, though it remains unclear if this is a class or drug-specific effect.
Why the study?
Does concomitant use of proton pump inhibitors reduce the antiplatelet efficacy of clopidogrel in patients with atherosclerotic and ischemic diseases?
Does concomitant use of proton pump inhibitors reduce the antiplatelet efficacy of clopidogrel in patients with atherosclerotic and ischemic diseases?
This review highlights the potential for proton pump inhibitors to attenuate the antiplatelet efficacy of clopidogrel via CYP2C19 inhibition, emphasizing the need for further prospective trials before altering clinical practice.
May prompt consideration of alternative gastroprotection with clopidogrel; leaves open whether CYP inhibition is class- or drug-specific.
Platelet activation and aggregation have been established as pivotal elements in the pathogenesis of atherosclerotic and ischemic diseases, including acute coronary syndromes. The difficulty of achieving optimal platelet inhibition remains a major constraint following dual-antiplatelet therapy, which can lead to a diminished response following initiation of clopidogrel therapy. Though the absolute mechanisms underlying clopidogrel resistance are controversial, a variety of responsible factors are recognized. Clopidogrel, being a prodrug, requires conversion to an active metabolite for its activity. This metabolism involves various cytochrome P450 (CYP) enzymes at different steps, and it is hypothesized that competitive inhibition of CYPs may contribute to clopidogrel resistance. Proton pump inhibitors (PPIs) are competitive inhibitors of CYPs that can attenuate the antiplatelet activity of clopidogrel, and this can lead to clopidogrel resistance. Available data from different clinical studies have postulated the possibility of a drug-drug interaction between clopidogrel and PPIs. PPIs differ somewhat in their pharmacokinetic properties like bioavaibility and affinity for CYP2C19. However it is not clear whether the proposed drug interaction of PPI with clopidogrel is same with all PPIs (i.e., a class effect) or it is limited to a subset of PPIs (i.e., a drug effect). This interaction needs further assessment with well designed prospective clinical trials, before any change in clinical practice should be considered. In this review, we attempt to evaluate the available evidence exploring drug interactions with PPIs as the underlying mechanism for the reduced antiplatelet effect of clopidogrel.
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Shah et al. (2012) conducted a review in Atherosclerotic and ischemic diseases. Proton pump inhibitors (PPIs) was evaluated. Proton pump inhibitors may attenuate the antiplatelet activity of clopidogrel by competitively inhibiting cytochrome P450 enzymes, though it remains unclear if this is a class or drug-specific effect.
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