DO PPIs INFLUENCE CLOPIDOGRELS PHARMACODYNAMIC EFFECTS?
As metabolism of both PPIs and clopidogrel involves CYP2C19 (and CYP3A4), and decreased metabolism of clopidogrel to its active metabolite is associated with poorer clinical outcomes, the potential influence of PPIs on the pharmacodynamic and clinical effects of clopidogrel were explored.Pharmacodynamic studies are summarized in Table 1. In a 2006 letter, Gilard et al., (45) using a novel surrogate marker for CV events (vasodilator-stimulated phosphoprotein phosphorylation platelet reactivity index (PRI)), reported higher PRI in patients taking clopidogrel plus PPI than in those taking clopidogrel without PPI. In a subsequent 7-day randomized, double-blind, placebo-controlled trial of omeprazole in clopidogrel users, these authors found significantly more poor responders, as measured by PRI, in the omeprazole group than in the placebo group (46). A randomized, crossover trial found that ADP-induced platelet aggregation was not significantly different with lansoprazole added to clopidog