Ticagrelor was not noninferior to prasugrel for the composite of death, MI, stroke, or major bleeding at 1 year (risk difference 2.33%; 95% CI -2.07 to 6.74; P=0.84 for noninferiority).
RCT (n=1,800)
Open-label
1:1
Yes
Does ticagrelor compared to prasugrel reduce the composite of death, nonfatal MI, stroke, or major bleeding in patients with diabetes and multivessel coronary artery disease undergoing percutaneous coronary intervention?
In patients with diabetes and multivessel coronary artery disease undergoing PCI, ticagrelor failed to show noninferiority to prasugrel for the primary composite outcome of death, MI, stroke, or major bleeding at 1 year.
Effect estimate: Risk difference 2.33 percentage points (95% CI -2.07 to 6.74)
Absolute Event Rate: 16.6% vs 14.2%
p-value: p=.84 for noninferiority
Importance The optimal dual antiplatelet therapy after percutaneous coronary intervention (PCI) in patients with diabetes is not clearly defined. Although both ticagrelor and prasugrel are potent inhibitors of P2Y purinergic receptor 12 (P2Y12), evidence directly comparing their efficacy and safety in this high-risk group remains limited. Objective To compare the clinical outcomes of ticagrelor vs prasugrel, each in combination with aspirin, in patients with diabetes and multivessel coronary artery disease who underwent percutaneous coronary intervention. Design, Setting, and Participants The Ultrathin Strut vs Xience in a Diabetic Population With Multivessel Disease 2—India Study (TUXEDO-2) is an investigator-initiated, prospective, open-label, multicenter, 2 × 2 factorial design, 1:1 randomized clinical trial. Participants with diabetes and multivessel disease undergoing percutaneous coronary intervention were enrolled at 66 clinical sites from February 2020 to August 2024. Interventions Patients undergoing percutaneous coronary intervention were randomized to receive either ticagrelor or prasugrel, each in combination with low-dose aspirin. Main Outcomes and Measures The primary outcome was a composite of death, nonfatal myocardial infarction, stroke, or major bleeding as defined by the Bleeding Academic Research Consortium at 1 year. The trial was designed to test the noninferiority of ticagrelor compared with prasugrel with a noninferiority margin of 5%. Results Among the 1800 participants randomized, mean (SD) age was 60 (10) years with 1296 (72.0%) male participants, 436 (24.2%) receiving insulin therapy, and 1530 (85.0%) with triple-vessel disease. At 1 year, the primary end point occurred in 129 participants (16.6%) taking ticagrelor and 107 participants (14.2%) taking prasugrel ( P = .12). The risk difference of 2.33 percentage points (95% CI, −2.07 to 6.74 percentage points) failed to meet the prespecified threshold for noninferiority ( P = .84). There was numerically higher (but not statistically significant) composite of death, myocardial infarction, stroke (10.43% vs 8.63%; P = .30), and major bleeding (8.41% vs 7.14%; P = .19) with ticagrelor when compared with prasugrel. Conclusions and Relevance In patients with diabetes and multivessel disease undergoing PCI, ticagrelor was not noninferior to prasugrel for the reduction of primary outcome at 1 year of follow-up. Trial Registration CTRI/2019/11/022088
The TUXEDO-2 trial, presented at AHA 2025 and recently discussed in expert analyses, compared two potent antiplatelet agents in a high-risk population, finding that a prasugrel-based strategy resulted in fewer ischemic and bleeding events than ticagrelor, challenging the notion of their interchangeability.
Bangalore et al. (Wed,) conducted a rct in Diabetes and multivessel coronary artery disease (n=1,800). Ticagrelor vs. Prasugrel was evaluated on Composite of death, nonfatal myocardial infarction, stroke, or major bleeding as defined by the Bleeding Academic Research Consortium at 1 year (Risk difference 2.33 percentage points, 95% CI -2.07 to 6.74, p=.84 for noninferiority). Ticagrelor was not noninferior to prasugrel for the composite of death, MI, stroke, or major bleeding at 1 year (risk difference 2.33%; 95% CI -2.07 to 6.74; P=0.84 for noninferiority).