Background Dual antiplatelet therapy (DAPT) is mandated in patients undergoing percutaneous coronary intervention (PCI). Enhanced platelet reactivity and impaired endogenous thrombolysis despite DAPT are risk factors for adverse cardiovascular events. The relative effects of different P2Y₁₂ inhibitors at high shear are incompletely understood.

Methods Thrombotic status was assessed with the automated point-of-care Global Thrombosis Test (GTT) in patients scheduled for PCI. Patients taking aspirin 75 mg daily were tested before and after being established on oral clopidogrel (n=20), ticagrelor (n=20) or having reached steady state on cangrelor infusion (n=15). The GTT assesses the time to form occlusive thrombus under high shear (occlusion time OT, sec) and the time taken to restore flow through endogenous thrombolysis of the occlusive thrombus (lysis time LT, sec).

Results All P2Y₁₂ inhibitors significantly prolonged OT compared to baseline, with the magnitude of effect greatest for cangrelor (mean increase in OT from baseline (delta): clopidogrel 83±120 vs ticagrelor 102±112 vs cangrelor 234±213; p=0.01). P2Y₁₂ inhibitors variably reduced LT, this was significant only for cangrelor (median change in LT (delta) from baseline: clopidogrel 30 [IQR-323, 260] vs ticagrelol 81 [-58, 259] vs cangrelor 309 [111, 764], p=0.041).

Conclusion Reduction in platelet reactivity in response to P2Y₁₂ inhibition varies between agents, with the greatest effect in response to cangrelor, followed by ticagrelor. Only cangrelor favourably enhanced endogenous thrombolysis.