Transitioning patients from cangrelor to clopidogrel: Pharmacodynamic evidence of a competitive effect

Steven R. Steinhubl, Jennifer J. Oh, Julie H. Oestreich, Suellen Ferraris, Richard Charnigo, Wendell S. Akers

Research output: Contribution to journalArticlepeer-review

162 Scopus citations


Background: Cangrelor is a direct, parenteral, and reversible inhibitor of the platelet P2Y12 receptor currently undergoing Phase III testing. As many individuals treated acutely with cangrelor will often be treated long-term with a thienopyridine, it is important to determine the effects of concurrent cangrelor and clopidogrel administration. Methods and results: Ten healthy volunteers received a 600 mg oral loading dose of clopidogrel and then underwent serial platelet function monitoring for 6 h. Two weeks later these same individuals received a 600 mg clopidogrel loading dose simultaneously with a cangrelor IV bolus (30 μg/kg) and a 2-hour infusion (4 μg/kg/min). A separate group of ten volunteers received a 600 mg clopidogrel loading dose after administration of a cangrelor bolus and a 1-hour infusion. The effects on ADP-induced platelet activation and aggregation were evaluated by flow cytometry, whole-blood electrical impedance, and light-transmittance aggregometry. Cangrelor and clopidogrel alone achieved the expected levels of platelet inhibition. However, the sustained platelet inhibition anticipated for clopidogrel treatment did not occur when cangrelor was initiated simultaneously. No such effect was found when clopidogrel was started upon completion of the cangrelor infusion. Conclusion: To achieve sustained platelet P2Y12 inhibition in patients treated with cangrelor, clopidogrel administration should be started when the cangrelor infusion is terminated.

Original languageEnglish
Pages (from-to)527-534
Number of pages8
JournalThrombosis Research
Issue number4
StatePublished - 2008


  • Angioplasty
  • Cangrelor
  • Coronary disease
  • P2Y inhibition
  • Platelets

ASJC Scopus subject areas

  • Hematology


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