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 JAMA Cardiology. 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 Cardiol. 2026 February 11 (Article in Press). Image Credit: Semi – stock.adobe.com