The optimal dual antiplatelet strategy after percutaneous coronary intervention (PCI) in patients with diabetes remains uncertain. The TUXEDO-2 trial was an investigator-initiated, prospective, open-label, multicenter, 2×2 factorial, 1:1 randomized clinical trial comparing ticagrelor and prasugrel, each combined with low-dose aspirin, in patients with diabetes and multivessel coronary artery disease undergoing PCI. The results of the trial were published in the JAMA Cardiology.

A total of 1800 participants were enrolled across 66 sites between February 2020 and August 2024. The mean (SD) age was 60 (10) years, 72% were men, 24% were receiving insulin therapy, and 85% had triple-vessel disease. The primary endpoint was a composite of death, nonfatal myocardial infarction, stroke, or major bleeding (Bleeding Academic Research Consortium criteria) at 1 year. The study was designed to assess noninferiority of ticagrelor compared with prasugrel using a 5% margin.

At 1 year, the primary endpoint occurred in 16.6% of ticagrelor-treated patients and 14.2% of prasugrel-treated patients (P=.12). The risk difference of 2.33 percentage points (95% CI, −2.07 to 6.74 percentage points) did not meet the prespecified noninferiority threshold (P=.84). The composite of death, myocardial infarction, or stroke occurred in 10.43% of patients receiving ticagrelor and 8.63% receiving prasugrel (P=.30), while major bleeding occurred in 8.41% vs 7.14%, respectively (P=.19).

These findings indicate that ticagrelor did not demonstrate noninferiority to prasugrel in this population.