New data presented at the American Heart Association (AHA) 2025 conference is prompting a reassessment of standard treatment protocols for patients with diabetes and multivessel coronary artery disease undergoing percutaneous coronary intervention (PCI). The TUXEDO-2 trial, conducted at 66 health centers in India and involving 1,800 adults, indicates that prasugrel-based dual antiplatelet therapy (DAPT) may offer superior protection against major cardiovascular events compared to ticagrelor-based DAPT in this high-risk population.
The trial focused on individuals with Type 1 or Type 2 diabetes and significant blockages in multiple coronary arteries who had received drug-eluting stents. Researchers found a numerically lower composite rate of heart attack, stroke, bleeding complications, or death in the prasugrel group (14.23%) versus the ticagrelor group (16.57%). Specifically, the rate of nonfatal heart attack was slightly lower with prasugrel (5.21%) compared to ticagrelor (5.96%), while major bleeding occurred less frequently among those taking prasugrel (7.14%) versus ticagrelor (8.41%). The mortality rate was too lower in the prasugrel group (3.67%) compared to the ticagrelor group (5.03%).
“Our findings indicate that prasugrel may potentially be the better choice for patients with Type 1 or Type 2 diabetes,” stated Sripal Bangalore, MD, MHA, FACC, the lead study author. “We were surprised by the results due to the fact that we hypothesized that ticagrelor should be as good or perhaps even better than prasugrel. It’s important to choose the right medicine, and at least from our data, we cannot say that ticagrelor and prasugrel are interchangeable.”
The TUXEDO-2 trial employed a 2×2 factorial design, simultaneously comparing different drug-eluting stents (Supraflex Cruz vs. Xience) alongside the two DAPT regimens. The primary endpoint for the DAPT arm was a composite of death, nonfatal myocardial infarction, stroke, or major bleeding, assessed at 12 months to determine non-inferiority. While ticagrelor did not demonstrate non-inferiority, exploratory analyses suggested a trend toward higher event rates with ticagrelor among patients with less than five years of diabetes and those considered at high bleeding risk.
The findings challenge previously held assumptions about the interchangeability of ticagrelor and prasugrel in diabetic patients with multivessel disease undergoing PCI. Approximately 25% of the study participants were taking insulin, 79% had experienced an acute coronary artery syndrome, and 85% had triple vessel disease, representing a complex and vulnerable patient cohort.
