• Eugene R Przespolewski, Erica S Westphal, Michelle Rainka, Nicholas M Smith, Vernice Bates, and Fran M Gengo.
• Dent Neurologic Institute, Amherst New York.
• J Stroke Cerebrovasc Dis. 2018 Jun 1; 27 (6): 1582-1589.

Background And GoalCytochrome P450 (CYP) enzymes are responsible for the conversion of clopidogrel into its active metabolite and the metabolism of proton pump inhibitors (PPIs), which may also inhibit CYP enzymes. A current Food and Drug Administration advisory suggests avoiding esomeprazole and omeprazole while taking clopidogrel because of concerns that PPIs may compromise clopidogrel's antiplatelet effects. The objective of the present study was to examine the robustness of this interaction using a well-controlled study design in a population of participants free of confounders.Materials And MethodsTwenty-eight healthy male participants, with a mean age 24.2 ± 3.2, were randomized to an incomplete crossover design schedule. Participants underwent platelet aggregation testing after clopidogrel alone, while on clopidogrel in combination with 1 of 3 PPIs (40 mg of pantoprazole, 20 mg of omeprazole, 20 mg of rabeprazole, 40 mg of esomeprazole, 30 mg of lansoprazole, or 30 mg of dexlansoprazole), and during 1 week of clopidogrel-only washout periods.FindingsThe median platelet aggregation to adenosine diphosphate during a drug-free baseline was 10Ω (2.5 interquartile range) of impedance and decreased to 0Ω on clopidogrel alone. Aggregation did not significantly change with concomitant use of PPIs and clopidogrel.ConclusionThese data do not demonstrate a significant interaction between common individual PPIs and clopidogrel in healthy volunteers who respond to clopidogrel alone. This adds data to a growing body of evidence indicating that the addition of a PPI may have a weak effect on clopidogrel's antiplatelet properties, and may only be relevant in specific clinical circumstances.Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

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