The TUXEDO-2 (Ultrathin Strut vs. Xience in a Diabetic Population With Multivessel Disease 2—India Study) trial demonstrated that among patients with diabetes mellitus and multivessel coronary artery disease undergoing percutaneous coronary intervention (PCI), a prasugrel-based dual antiplatelet therapy strategy resulted in fewer ischemic and bleeding events compared with ticagrelor, with ticagrelor failing to meet prespecified noninferiority criteria. At 12 months, the composite endpoint of death, nonfatal myocardial infarction, stroke, or major bleeding occurred more frequently in patients who received ticagrelor, suggesting a clinical advantage of prasugrel in this high-risk population.¹

TUXEDO-2 was a multicenter, randomized trial conducted in India that enrolled 1,800 patients with diabetes mellitus (mean age, 60 years; 28% women) and angiographically confirmed multivessel coronary artery disease who underwent PCI with contemporary drug-eluting stents.¹ Approximately 79% of patients had acute coronary syndrome. Patients were randomized to receive ticagrelor plus aspirin or prasugrel plus aspirin, and in a 2×2 factorial design to an ultrathin biodegradable polymer sirolimus-eluting stent versus a durable polymer everolimus-eluting stent. At 12 months, the composite event rates were higher with ticagrelor than prasugrel (16.6% vs. 14.2%), including numerically greater rates of nonfatal myocardial infarction (5.96% vs. 5.21%), major bleeding (8.41% vs. 7.14%), and death (5.03% vs. 3.67%). At 1 year, rates of target lesion failure were similar between the ultrathin biodegradable polymer stent and durable polymer stent groups, meeting criteria for noninferiority.¹

TUXEDO-2 adds to growing evidence that potent P2Y purinergic receptor 12 (P2Y12) inhibitors may not be interchangeable in patients with diabetes mellitus undergoing PCI, a population with heightened ischemic and bleeding risk. These findings are consistent with prior trials demonstrating favorable ischemic outcomes with prasugrel in select high-risk cohorts.² Limitations of the study include its conduct within a single country and lack of long-term follow-up beyond 1 year. Future studies should focus on longer-term outcomes, individualized antiplatelet selection strategies that balance ischemic and bleeding risks, and validation in broader and more diverse populations.

References

1. Bangalore S, Sinha SK, Singh R, et al. Ticagrelor vs prasugrel in patients with diabetes and multivessel coronary artery disease: the TUXEDO-2 randomized clinical trial. JAMA Cardiol. 2026;11(4):369-377. doi:10.1001/jamacardio.2025.5057
2. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357(20):2001-2015. doi:10.1056/NEJMoa0706482