Ticagrelor is not noninferior to prasugrel in reducing negative clinical outcomes in patients with diabetes who also have multivessel disease, results from the TUXEDO-2 trial show. Negative clinical outcomes in this study include death, nonfatal myocardial infarction (MI), stroke or major bleeding at 1-year follow-up after percutaneous coronary intervention (PCI). Sripal Bangalore, MD, MHA, of NYU Langone Heath and NYU Grossman School of Medicine, New York, and colleagues, reported the corresponding data in a manuscript published online Wednesday in the Journal of the American Medical Association. The best dual antiplatelet therapy after PCI for patients with diabetes is unknown. No evidence has presented the comparison of ticagrelor versus prasugrel — two P2Y purinergic receptor 12 (P2Y12) inhibitors — in this patient group. The randomized, prospective, investigator-initiated, open-label, multicenter TUXEDO-2 (The Ultrathin Strut vs Xience in a Diabetic Population With Multivessel Disease 2) clinical trial examined patients with diabetes and multivessel disease who underwent PCI across 66 sites between February 2020 and August 2024. Patients were randomized 1:1 to receive either ticagrelor or prasugrel plus a low dose of aspirin. The trial tested the noninferiority of ticagrelor compared with prasugrel. Death, nonfatal MI, stroke or major bleeding (defined by the Bleeding Academic Research Consortium) at 1-year post-PCI. A total of 1,800 patients were randomized (mean age=60 years, 72.0% male), and significant conditions across all participants included receiving insulin therapy (n=436) and triple vessel disease (n=1,530). At 1-year follow-up, 16.6% of ticagrelor patients experienced the primary endpoint, and 14.2% of prasugrel patients experienced the primary endpoint (p=0.12; risk difference=2.33 percentage points, 95% confidence interval [CI]:-2.07 to 6.74 percentage points). This did not meet the threshold for noninferiority (p=0.84). Numerically, rates of the composite of death, MI or stroke (10.43% vs 8.63%, p=0.30) and major bleeding (8.41% vs 7.14%, p=0.19) were higher in patients with ticagrelor versus prasugrel, but these were not statistically significant. Limitations of this study include the open-label design, compliance with medication was not assessed, subgroups and individual endpoints were not powered and should be considered hypothesis-generating, the results may not be generalizable to other cohorts since this study intended to optimize PCI with guideline-directed medical therapy, eight patients with prior stroke were given prasugrel despite a black box warning against it and two patients were switched to ticagrelor from prasugrel. Ticagrelor proved not noninferior to prasugrel when given to patients with diabetes post-PCI, along with aspirin to complete the dual antiplatelet therapy recommendations. The investigators noted that this demonstrates how prasugrel is still superior in this patient population. Source: Bangalore S, Sinha SK, Singh R, et al. Ticagrelor vs prasugrel in patients with diabetes and multivessel coronary artery disease. JAMA. 2026 February 11 (Article in Press). Image Credit: Semi – stock.adobe.com