Pharmacodynamic Effects When Clopidogrel is Given Before Cangrelor Discontinuation

J Interv Cardiol. 2015 Oct;28(5):415-9. doi: 10.1111/joic.12229. Epub 2015 Sep 18.

Abstract

Objective: To determine whether initiation of clopidogrel before discontinuation of cangrelor would impact on the recovery of platelet reactivity.

Background: The active metabolite of clopidogrel cannot bind to P2Y12 when cangrelor occupies the receptor. Pharmacodynamic studies have shown that this interaction is avoided when clopidogrel is given at the end of the cangrelor infusion. We found that antiplatelet effects of another thienopyridine, prasugrel, were apparent when prasugrel was administered 0.5 hour before cangrelor was stopped.

Methods: Platelet function studies (light transmission aggregometry, VerifyNow, and flow cytometry) were performed on blood from patients with stable coronary artery disease who were taking aspirin when a loading dose of clopidogrel (600 mg) was given during a cangrelor infusion (0.5 and 1 hour before cangrelor was stopped). Results were compared with those obtained when clopidogrel was given immediately after cangrelor was stopped.

Results: Administration of clopidogrel 0.5 and 1 hour before discontinuation of the cangrelor infusion did not prevent recovery of platelet reactivity more effectively than administration at the end of the infusion.

Conclusion: Our results support the previously established strategy of administering clopidogrel immediately after discontinuation of cangrelor. Earlier administration increases the recovery of platelet function.

Trial registration: ClinicalTrials.gov NCT01979445.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Monophosphate / administration & dosage
  • Adenosine Monophosphate / analogs & derivatives*
  • Adenosine Monophosphate / pharmacokinetics
  • Adult
  • Aged
  • Biological Availability
  • Blood Platelets / drug effects
  • Clopidogrel
  • Coronary Artery Disease* / blood
  • Coronary Artery Disease* / drug therapy
  • Drug Interactions
  • Female
  • Humans
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care
  • Platelet Activation / drug effects*
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / pharmacokinetics
  • Platelet Function Tests / methods
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacokinetics

Substances

  • Platelet Aggregation Inhibitors
  • Adenosine Monophosphate
  • cangrelor
  • Clopidogrel
  • Ticlopidine

Associated data

  • ClinicalTrials.gov/NCT01979445