Key Points
- TUXEDO-2 directly compared ticagrelor vs prasugrel based DAPT in 1,800 patients with diabetes and multivessel coronary artery disease (MVD) undergoing PCI with drug-eluting stents.
- Conducted across 66 centers in India, the trial included patients with Type 1 or Type 2 diabetes (median age 60 years; 29% women).
- Prasugrel-based DAPT demonstrated a numerically lower composite rate of death, MI, stroke, or major bleeding than ticagrelor-based DAPT (14.23% vs 16.57%).
- Findings suggest that prasugrel may be the preferred agent in this high-risk population, challenging assumptions of equivalence between potent P2Y12 inhibitors.
Optimal P2Y12 inhibitor selection in patients with diabetes and multivessel CAD undergoing PCI remains uncertain. Both ticagrelor and prasugrel are potent agents proven superior to clopidogrel, yet direct comparative data in this complex, high-risk population have been lacking.
At the American Heart Association 2025 Scientific Sessions, Dr. Sripal Bangalore (NYU Langone, New York) presented the TUXEDO-2 trial, which evaluated clinical outcomes between ticagrelor- and prasugrel-based dual antiplatelet therapy (DAPT) regimens in diabetic patients undergoing PCI.
TUXEDO-2 was a prospective, multicenter, open-label, randomized controlled trial conducted across 66 health centers in India. The trial enrolled 1,800 adults with Type 1 or Type 2 diabetes and angiographically confirmed multivessel disease, all undergoing PCI with a drug-eluting stent (Supraflex Cruz SES or Xience EES). Patients were randomized 1:1 to receive either ticagrelor-based DAPT (ticagrelor + aspirin), or prasugrel-based DAPT (prasugrel + aspirin). Approximately 25% of participants were insulin-dependent, 79% presented with acute coronary syndrome (ACS), and 85% had triple-vessel disease. The primary endpoint was a composite of death, myocardial infarction, stroke, or major bleeding at 12 months, defined using BARC criteria. The composite rate of death, myocardial infarction, stroke, or major bleeding was numerically lower in the prasugrel group compared with the ticagrelor group (14.23% vs 16.57%).
When outcomes were analyzed individually, nonfatal MI was reported 5.96% in ticagrelor group vs 5.21% in the prasugrel group, major bleeding was 8.41% vs 7.14% in the favor of prasugrel and most importantly mortality was also in the favor of prasugrel (5.03% vs 3.67%). These findings suggest that prasugrel may provide a more favorable overall balance between ischemic protection and bleeding risk in patients with diabetes and MVD undergoing PCI.
According to Dr. Sripal Bangalore, “We were surprised by the results because 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.” Dr. Bangalore added that the TUXEDO-2 results build upon earlier evidence from TUXEDO-1 and highlight the need for nuanced antiplatelet selection strategies in diabetic patients with multivessel disease, a subset with particularly high ischemic and thrombotic burden. With the prasugrel-based DAPT yielding numerically fewer major adverse events, these findings may influence future DAPT selection guidelines for complex diabetic patients.