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

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 P2Y12-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).

Comparison of Immature Platelet Count to Established Predictors of Platelet Reactivity During Thienopyridine Therapy.

BACKGROUND: Previous data suggest that reticulated platelets significantly affect antiplatelet response to thienopyridines. It is unknown whether parameters describing reticulated platelets can predict antiplatelet response to thienopyridines. OBJECTIVES: The authors sought to determine the extent to which parameters describing reticulated platelets can predict antiplatelet response to thienopyridine loading compared with established predictors. METHODS: This study randomized 300 patients undergoing elective coronary stenting to loading with clopidogrel 600 mg, prasugrel 30 mg, or prasugrel 60 mg. Adenosine diphosphate (ADP)-induced platelet reactivity was assessed by impedance aggregometry before loading (intrinsic platelet reactivity) and again on day 1 after loading. Multiple parameters of reticulated platelets were assessed by automated whole blood flow cytometry: absolute immature platelet count (IPC), immature platelet fraction, and highly fluorescent immature platelet fraction. RESULTS: Each parameter of reticulated platelets correlated significantly with ADP-induced platelet reactivity (p < 0.01 for all 3 parameters). In a multivariable model including all 3 parameters, only IPC remained a significant predictor of platelet reactivity (p < 0.001). In models adjusting each of the 3 parameters for known predictors of on-treatment platelet reactivity including cytochrome P450 2C19 (CYP2C19) polymorphisms, age, body mass index, diabetes, and intrinsic platelet reactivity, only IPC prevailed as an independent predictor (p = 0.001). In this model, IPC was the strongest predictor of on-treatment platelet reactivity followed by intrinsic platelet reactivity. CONCLUSIONS: IPC is the strongest independent platelet count-derived predictor of antiplatelet response to thienopyridine treatment. Given its easy availability, together with its even stronger association with on-treatment platelet reactivity compared with known predictors, including the CYP2C19*2 polymorphism, IPC may become the preferred predictor of antiplatelet response to thienopyridine treatment. (Impact of Extent of Clopidogrel-Induced Platelet Inhibition During Elective Stent Implantation on Clinical Event Rate-Advanced Loading Strategies [ExcelsiorLOAD]; DRKS00006102).

Randomized Comparison of Different Thienopyridine Loading Strategies in Patients Undergoing Elective Coronary Intervention: The ExcelsiorLOAD Trial.

OBJECTIVES: This randomized trial investigated to what extent loading with prasugrel can provide a more rapid peri-interventional antiplatelet effect than clopidogrel 600 mg. BACKGROUND: Effective platelet inhibition at the start of a percutaneous coronary intervention (PCI) reduces the risk of ischemic complications. With clopidogrel administered immediately before a PCI, effective platelet inhibition is delayed by 2 h. Prasugrel has the potential of shortening this period. METHODS: We randomly assigned 300 P2Y12 receptor blocker-naive patients undergoing an elective PCI to loading with clopidogrel 600 mg, prasugrel 30 mg, or prasugrel 60 mg immediately before the PCI. Platelet function was assessed serially by impedance aggregometry. The primary endpoint was the proportion of patients with high on-treatment platelet reactivity at 60 min after loading defined as ≥468 aggregation units × minute (Multiplate Analyzer, Roche Diagnostics, Mannheim, Germany). RESULTS: The 3 groups were well balanced with respect to clinical and angiographic characteristics. At 60 min, 33% of the patients assigned to prasugrel 60 mg, 37% of patients assigned to prasugrel 30 mg, but 55% of those assigned to clopidogrel had high on-treatment platelet reactivity (p < 0.001). At any time point starting from 30 min, prasugrel 60 mg achieved significantly lower platelet reactivity than clopidogrel. Platelet reactivity at 60 min after prasugrel was not significantly different from that at 120 min after clopidogrel (p = 0.18). Prasugrel 30 mg had an intermediate effect. The 30-day incidence of bleeding events was not different among the 3 groups. CONCLUSIONS: From 30 min onward, prasugrel 60 mg achieved a stronger platelet inhibition than clopidogrel loading in stable patients undergoing a PCI. Compared with clopidogrel, prasugrel 60 mg was associated with a twice as fast onset of platelet inhibition. (Impact of Extent of Clopidogrel-Induced Platelet Inhibition during Elective Stent Implantation on Clinical Event Rate-Advanced Loading Strategies [ExcelsiorLOAD]; DRKS00006102).