Randomized Comparison of Oral P2Y12-Receptor Inhibitor Loading Strategies for Transitioning From Cangrelor: The ExcelsiorLOAD2 Trial

Abstract Objectives This randomized trial tested whether early loading with prasugrel can provide sufficient platelet inhibition even when given at the start of a 2-h infusion of cangrelor. Background Effective platelet inhibition with intravenous cangrelor reduces the risk of ischemic complications during percutaneous coronary intervention (PCI). Transitioning to oral therapy with clopidogrel or prasugrel is only recommended after discontinuation of cangrelor due to drug interactions. Given the long half-life of prasugrel, this drug could achieve effective platelet inhibition even when given early under cangrelor and thereby prevent a transient gap in platelet inhibition. Methods This trial randomized 110 P2Y 12 -receptor blocker–naive patients undergoing PCI with use of cangrelor to loading with prasugrel 60 mg or ticagrelor 180 mg at the start of cangrelor (n = 45 each) or loading with clopidogrel 600 mg after discontinuation of cangrelor (n = 20). The primary endpoint was the proportion of patients without high on-treatment platelet reactivity 1 h after stopping cangrelor. Results The 3 groups were well balanced with respect to clinical parameters. One hour following discontinuation of cangrelor, the primary endpoint was seen in 65.0% of patients on clopidogrel versus 95.6% with ticagrelor and 93.3% with prasugrel (p for superiority of prasugrel vs. clopidogrel = 0.003; p of prasugrel vs. ticagrelor = 0.65). The 30-day incidence of ischemic and bleeding events was similar in all groups. Conclusions Prasugrel 60 mg given at the start of a 2-h infusion of cangrelor can provide a sufficient platelet inhibition post-cangrelor. This approach prevents the transient gap in platelet inhibition seen with oral loading after discontinuation of cangrelor. (Impact of Extent of Clopidogrel-Induced Platelet Inhibition during Elective Stent Implantation on Clinical Event Rate – Advanced Loading Strategies [ExcelsiorLOAD2]; DRKS00009739)