title: Antiplatelet drug interactions with proton pump inhibitors.
abstract: BACKGROUND
  Non-aspirin antiplatelet agents (e.g., clopidogrel, prasugrel, ticagrelor) are commonly prescribed for the prevention of recurrent cardiovascular events among patients with acute coronary syndromes (ACS) and/or those undergoing percutaneous coronary intervention (PCI). In addition, combination therapy with proton pump inhibitors (PPIs) is often recommended to attenuate gastrointestinal bleeding risk, particularly during dual antiplatelet therapy (DAPT) with clopidogrel and aspirin. Importantly, a pharmacological interaction between clopidogrel and some PPIs has been proposed based on mutual CYP450-dependent metabolism, but available evidence is inconsistent.
  
  
  METHODS
  This article provides an overview of the currently approved antiplatelet agents and PPIs, including their metabolic pathways. Additionally, the CYP450 isoenzyme at the center of the drug interaction, CYP2C19, is described in detail, and the available evidence on both the potential pharmacological interaction and influence on clinical outcomes are summarized and evaluated.
  
  
  CONCLUSIONS
  Although concomitant DAPT and PPI use reduces clopidogrel active metabolite levels and ex vivo-measured platelet inhibition, the influence of the drug interaction on clinical outcomes has been conflicting and largely reported from non-randomized observational studies. Despite this inconsistency, a clinically important interaction cannot be definitively excluded, particularly among patient subgroups with higher overall cardiovascular risk and potentially among CYP2C19 loss-of-function allele carriers.
authors.affiliation: Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences , One Gustave L. Levy Place, Box 1497, New York, NY 10029 , USA +1 212 241 3780 ; +1 212 241 0139 ; stuart.scott@mssm.edu.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Scott
authors.forename: Aniwaa
authors.initials: A
authors.lastname: Owusu Obeng
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Hulot
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D004347:Drug Interactions / Q000502:physiology; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D054328:Proton Pump Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors