Current Cardiology Reports

, 13:451

Thienopyridine-Associated Drug-Drug Interactions: Pharmacologic Mechanisms and Clinical Relevance

  • Jean-Sébastien Hulot
  • Jean-Philippe Collet
  • Gilles Montalescot

DOI: 10.1007/s11886-011-0206-1

Cite this article as:
Hulot, JS., Collet, JP. & Montalescot, G. Curr Cardiol Rep (2011) 13: 451. doi:10.1007/s11886-011-0206-1


The thienopyridines inhibit platelet activation and aggregation by directly inhibiting the platelet P2Y12 adenosine diphosphate receptor. The available thienopyridines are prodrugs and must be converted into active forms by the cytochrome P450 (CYP) enzyme system. An important portion of the variability in platelet response to clopidogrel is explained by the variability in plasma concentrations of the clopidogrel active metabolite. Several reports have thus progressively raised concerns about potential drug interactions as a result of inhibition or induction of CYP450 enzymes. Pharmacokinetics and pharmacodynamics studies have notably shown that concomitant use of clopidogrel and some proton pump inhibitors reduces the antiplatelet effect of clopidogrel. Several other drugs (metabolized through CYP3A4 such as statins or antifungals) similarly impact the pharmacologic response to clopidogrel. Conversely, agents that induce CYP activity increase clopidogrel responsiveness. However, the data supporting the clinical relevance of such pharmacological drug interactions have been controversial. This review will provide an overview of the mechanisms underlying thienopyridine-associated drug-drug interactions, and highlight the most recent developments in the field and propose guidance for the practitioner.


Platelet aggregation P2Y12 antagonists Thienopyridines Coronary disease Drug interactions Polypharmacy Pharmacokinetics Proton pump inhibitors 

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Jean-Sébastien Hulot
    • 1
    • 2
  • Jean-Philippe Collet
    • 3
  • Gilles Montalescot
    • 3
    • 4
  1. 1.Cardiovascular Research Center, Mount Sinai School of MedicineNew YorkUSA
  2. 2.UPMC Univ Paris 06ParisFrance
  3. 3.Institut de Cardiologie, INSERM UMR_S 937, Pitié-Salpêtrière Hospital (AP-HP)ParisFrance
  4. 4.Institut de Cardiologie-Bureau 236 Hôpital Pitié-Salpêtrière, 47, bd de l’HôpitalParisFrance

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