The Influence of Proton Pump Inhibitors on the Antiplatelet Potency of Clopidogrel Evaluated by 5 Different Platelet Function Tests

Abstract

Proton pump inhibitors (PPIs) are metabolized by the cytochrome P450 enzyme system to a variable degree and may therefore interact with the metabolism of clopidogrel to its active form. The conflicting data on this potential interaction may be due to the use of different PPIs and platelet function tests in recent studies. We therefore evaluated the influence of different PPIs on the antiplatelet effect of clopidogrel by 5 platelet function tests in the same population. Adenosine diphosphate (ADP)-inducible platelet reactivity was assessed in 230 patients on dual antiplatelet therapy after angioplasty and stenting for cardiovascular disease by the light transmission aggregometry, VerifyNow P2Y12 assay, vasodilator-stimulated phosphoprotein phosphorylation assay, multiple electrode aggregometry, and Impact-R. ADP-inducible platelet reactivity showed no significant differences between patients without (n = 95, 41.3%) and with PPI therapy (n = 135, 58.7%) in each test system (all P > 0.05). Furthermore, we observed no significant differences of ADP-inducible platelet reactivity between patients without PPIs and patients with pantoprazole (n = 95, 70.4%), esomeprazole (n = 22, 16.3%), omeprazole (n = 9, 6.65%), or lansoprazole (n = 9, 6.65%) (all P > 0.3). High on-treatment residual ADP-inducible platelet reactivity occurred to a similar extent in patients without and with PPI therapy in each assay (all P > 0.05). In conclusion, concomitant treatment with PPIs did not attenuate the antiplatelet effect of clopidogrel in patients on dual antiplatelet therapy irrespective of the type of PPI and the used test system.