Dual resistance to ticagrelor and prasugrel leading to subacute stent thrombosis: a diagnostic and therapeutic challenge

Stent thrombosis (ST) may occur due to variability in platelet response to P2Y12 inhibitors, particularly after excluding common causes such as mechanical complications or medication non-compliance. Although ticagrelor and prasugrel typically provide more potent and consistent platelet inhibition than clopidogrel, some individuals still demonstrate inadequate response due to drug resistance. We describe a healthy, non-smoking male in his mid-60s who developed subacute ST 4 days after drug-eluting stent placement while on dual antiplatelet therapy with aspirin and ticagrelor. After excluding mechanical and clinical aetiologies, ticagrelor resistance was suspected. His regimen was switched to aspirin and prasugrel; however, thromboelastography (TEG) platelet mapping demonstrated persistently high on-treatment platelet reactivity to prasugrel, even after doubling the prasugrel dose. This case highlights rare resistance to newer P2Y12 inhibitors as a cause of unexplained ST and underscores the value of TEG platelet mapping to identify antiplatelet non-responsiveness and guide individualised therapy.