Prasugrel vs. Ticagrelor: Can TUXEDO-2 Settle the Debate?

Prasugrel and ticagrelor are potent oral P2Y12 inhibitors that carry a Class I recommendation for patients with acute coronary syndromes undergoing percutaneous coronary intervention, providing faster and more consistent platelet inhibition than clopidogrel. Despite identical guideline positioning, the optimal choice between the two agents has long remained unsettled, largely because head-to-head randomized data were scarce and the agents were assumed to be clinically interchangeable. That assumption is now substantially challenged by two large randomized trials (ISAR-REACT 5 and TUXEDO-2) whose convergent findings consistently point in the same direction. Here, we argue that the accumulated pharmacological and clinical evidence builds a coherent, mechanistically grounded case for the preferential use of prasugrel in appropriately selected patients, and that persisting therapeutic inertia against this drug is no longer scientifically defensible.