Choosing the optimal P2Y12 inhibitor for diabetic patients with multivessel coronary artery disease undergoing percutaneous coronary intervention (PCI) remains a major clinical challenge. These patients face both high ischemic risk and increased bleeding susceptibility, which requires precise therapeutic balance. Direct comparative evidence between ticagrelor and prasugrel in this context has been limited.

The TUXEDO-2 trial was a multicenter, randomized study with a 2×2 factorial design simultaneously comparing two sets of techniques:
- Drug-eluting stents (Supraflex Cruz vs. Xience)
- Dual antiplatelet therapy (DAPT) — ticagrelor + aspirin (ASA) vs. prasugrel + ASA
The population included diabetic patients with multivessel coronary disease treated with PCI. The primary endpoint for the DAPT arm was a composite of death, nonfatal myocardial infarction (MI), stroke, or major bleeding, assessed at 12 months for non-inferiority.
Upon primary analysis, ticagrelor (n=901) showed a composite event rate of 16.57%, vs 14.23% for prasugrel (n=899) (absolute difference +2.33%; upper limit 95% CI 6.74%), though without reaching non-inferiority. The exploratory analyses suggested a trend towards higher events rate with ticagrelor among diabetic patients with less than 5-year evolution, and those at high bleeding risk.
Conclusion
In diabetic patients with multivessel disease undergoing PCI, ticagrelor + AAS was not shown non-inferior vs prasugrel + AAS for the composite of ischemia and bleeding at 12 months, with numerically better outcomes for prasugrel.
Presented by Sripal Bangalore, Late-Breaking Science Session, AHA 2025, New Orleans, USA.
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