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 microg/kg) and a 2-hour infusion (4 microg/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 withcangrelor, clopidogrel administration should be started when the cangrelor infusion is terminated.
RCT Entities:
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 microg/kg) and a 2-hour infusion (4 microg/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.
Authors: Dominick J Angiolillo; David J Schneider; Deepak L Bhatt; William J French; Matthew J Price; Jorge F Saucedo; Tamaz Shaburishvili; Kurt Huber; Jayne Prats; Tiepu Liu; Robert A Harrington; Richard C Becker Journal: J Thromb Thrombolysis Date: 2012-07 Impact factor: 2.300
Authors: Kiran Kalra; Christopher J Franzese; Martin G Gesheff; Eli I Lev; Shachi Pandya; Kevin P Bliden; Udaya S Tantry; Paul A Gurbel Journal: Curr Atheroscler Rep Date: 2013-12 Impact factor: 5.113
Authors: Christopher R Kelly; Ajay J Kirtane; Jennifer Stant; Gregg W Stone; Robert M Minutello; S Chiu Wong; Honeyleen Manuzon; Roxanne Gerow-Smith; Nancy Kelley; LeRoy E Rabbani Journal: Crit Pathw Cardiol Date: 2017-03