Ticagrelor Versus Prasugrel in Diabetes and Multivessel Coronary Disease: Insights From the TUXEDO-2 Trial

Patients with diabetes mellitus and multivessel coronary artery disease represent a high-risk subgroup in acute coronary syndromes (ACS) requiring optimal antiplatelet therapy. Dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor is the standard of care after percutaneous coronary intervention to prevent stent thrombosis and recurrent ischemic events. Ticagrelor and prasugrel are potent P2Y12 inhibitors that have each demonstrated superior efficacy over clopidogrel in large trials, though their comparative merits have been debated, especially in complex diabetic populations. This review provides background on antiplatelet therapy in ACS, with an emphasis on patients with diabetes and complex coronary anatomy; summarizes key pharmacologic differences and pivotal trial data for ticagrelor and prasugrel (including Platelet Inhibition and Patient Outcomes, TRITON-TIMI 38, and ISAR-REACT 5); and examines the design and findings of the recent TUXEDO-2 trial. TUXEDO-2, conducted in patients with diabetes with multivessel disease undergoing percutaneous coronary intervention, ticagrelor failed to meet noninferiority compared with prasugrel for a composite of ischemic and bleeding outcomes. The trial's results, in context with prior evidence, suggest that prasugrel may provide better net clinical outcomes than ticagrelor in this high-risk group. We discuss the clinical implications of these findings for managing ACS in diabetic patients.