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

Cangrelor inhibits the binding of the active metabolites of clopidogrel and prasugrel to P2Y12receptorsin vitro

“…In agreement with in vitro studies assessing platelet function [14,15] when platelets encounter thienopyridine AMs in the presence of cangrelor, the ability of the thienopyridine AM to block the P2Y 12 receptor is greatly reduced.…”

“…Several studies have examined the transition from cangrelor to thienopyridines and have shown a transient recovery of platelet reactivity during the switch from cangrelor to either clopidogrel or prasugrel [14,17]. A recent study by Schneider et al demonstrated a transient recovery in platelet function in patients with stable coronary artery disease during the transition from cangrelor to prasugrel but this effect was limited if prasugrel was administered 30min before the end of cangrelor infusion [17].…”

“…In a healthy volunteer study, the ability of clopidogrel to inhibit platelet aggregation was reduced if it was administered during a cangrelor infusion [14]. Cangrelor was also found to limit the inhibition of platelet activation (measured by P selectin expression) by prasugrel AM in in vitro studies [15].…”

New P2Y 12 Inhibitors

“…However, for long-term prevention, these patients should be treated with orally available agents. Steinhubl et al 34 demonstrated that the simultaneous administration of intravenous cangrelor with an oral 600-mg loading dose of clopidogrel prevents the expected inhibition of platelet aggregation by clopidogrel, presumably as a result of competitive interaction between cangrelor and the active metabolite of clopidogrel at the P2Y 12 receptor level. Therefore, it was suggested that the clopidogrel loading dose should be administered after termination of cangrelor infusion.…”

Cangrelor for the management and prevention of arterial thrombosis

“…Due to the differences in pharmacological activity, it was important to investigate the ability of oral thienopyridines to inhibit platelet function when administered simultaneously with and immediately after cangrelor infusion. This was carried out by Steinhubl et al using clopidogrel as the oral agent; although no drug-related adverse events were identified in either treatment arm, it was seen that when clopidogrel and cangrelor were administered simultaneously, clopidogrel was unable to effectively inhibit platelet function, even at a 600mg loading dose [41]. The interaction was minimised when the clopidogrel loading dose was administered at the time of cessation of cangrelor infusion.…”