Ticagrelor Not Noninferior to Prasugrel After PCI in Diabetes: JAMA
In a recent study, ticagrelor was found to be noninferior to prasugrel for a composite of ischemic events including death, myocardial infarction, stroke, and major bleeding after a year in a population suffering from diabetes and multivessel coronary artery disease and undergoing percutaneous coronary intervention. It was found that the major endpoint was numerically higher in the ticagrelor group, which emphasizes that ticagrelor did not exhibit similar efficacy to prasugrel. The study was published in JAMA Cardiology by Sripal B. and colleagues.
The best combination of dual antiplatelet therapy (DAPT) after PCI in diabetic subjects is unknown. Both ticagrelor and prasugrel are potent P2Y12 antagonists frequently used with aspirin. To date, few data have compared these two drugs directly to assess their efficacy and safety in diabetic subjects with multivessel coronary artery disease, a population at high risk of thrombotic and bleeding complications. A comparison of these two agents was considered to be of clinical importance.
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 2x2 factorial 1:1 randomised clinical trial with 66 clinical sites. The trial participants were enrolled between February 2020 and August 2024. The trial enrolled participants who had a diabetic condition and multivessel disease and were undergoing a PCI. The participants were randomly assigned to take either Ticagrelor or Prasugrel with Low-Dose Aspirin.
In total, there were 1800 participants who were randomly chosen. The mean and standard deviation of the age were found to be 60 and 10 years, respectively. In addition, there were 1296 males (72.0%) in the study. Also, there were 436 (24.2%) patients who were on insulin therapy in the cohort, and 1530 patients (85.0%) were found to have triple vessel disease.
The key endpoint included a composite of death, nonfatal myocardial infarction, stroke, or major bleeding as defined by the Bleeding Academic Research Consortium by 1 year. The trial aimed to determine noninferiority, with a margin of 5%, between ticagrelor and prasugrel.
Key findings
In 1800 randomized patients the primary composite endpoint at 1 year occurred in 16.6% of patients receiving ticagrelor and 14.2% receiving prasugrel (P = 0.12).
The absolute risk difference was 2.33 percentage points (95% CI, −2.07 to 6.74), and noninferiority was not established (P = 0.84).
The composite of death, myocardial infarction, or stroke occurred in 10.43% vs 8.63% (P = 0.30), and major bleeding occurred in 8.41% vs 7.14% (P = 0.19) in the ticagrelor and prasugrel groups, respectively.
In patients with diabetes and multivessel coronary artery disease undergoing PCI, ticagrelor did not demonstrate non-inferiority to prasugrel in preventing a combination of death, non-fatal myocardial infarction, stroke, or major bleeding at 1 year. These results provide head-to-head comparative insights that may help to shape clinical decisions on dual antiplatelet therapy in these high-risk patients.
Reference:
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. Published online February 11, 2026. doi:10.1001/jamacardio.2025.5057
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