A large randomized clinical trial has revealed significant differences in effectiveness between two commonly prescribed antiplatelet medications in diabetic patients following coronary stent placement, challenging current clinical practice that treats these drugs as interchangeable.
The TUXEDO-2 study, presented at the American Heart Association's Scientific Sessions 2025, compared ticagrelor and prasugrel in 1,800 adults with Type 1 or Type 2 diabetes and multivessel coronary artery disease who had undergone percutaneous coronary intervention (PCI) with drug-eluting stent placement.
Key Trial Findings
The study demonstrated that prasugrel-based dual antiplatelet therapy (DAPT) provided superior outcomes compared to ticagrelor-based therapy. The primary composite outcome of heart attack, stroke, bleeding complications, or death occurred in 14.23% of patients receiving prasugrel versus 16.57% of those receiving ticagrelor.
Breaking down the individual outcomes, the ticagrelor group experienced higher rates across all measured endpoints: nonfatal heart attack occurred in 5.96% of ticagrelor patients compared to 5.21% in the prasugrel group, major bleeding affected 8.41% versus 7.14% respectively, and death rates were 5.03% versus 3.67%.
"Our findings indicate that prasugrel may potentially be the better choice for patients with Type 1 or Type 2 diabetes," said lead study author Sripal Bangalore, MD, MHA, FAHA, a professor of medicine at NYU Grossman School of Medicine. "We were surprised by the results because we hypothesized that ticagrelor should be as good or perhaps even better than prasugrel."
Study Design and Population
Conducted across 66 healthcare centers in India from 2020 to 2024, the trial enrolled patients with a median age of 60 years, with 71% men and 29% women. The study population represented a high-risk cohort: approximately 25% were taking insulin, 79% had acute coronary syndrome, and 85% had triple vessel disease.
All participants had undergone PCI with drug-eluting stent implantation and were prescribed dual antiplatelet therapy consisting of aspirin plus either ticagrelor or prasugrel for one year, following current guideline recommendations.
Clinical Implications
The findings challenge the current clinical approach of treating ticagrelor and prasugrel as equivalent options. "Currently, these medications are treated as interchangeable. However, our findings provide evidence that they might be a bit different," Bangalore noted. "For individuals with Type 1 or Type 2 diabetes and complex coronary disease, there may be an advantage to treatment with prasugrel over ticagrelor, and importantly, the two should not be used interchangeably."
The 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes recommends at least one year of dual antiplatelet therapy for all patients after drug-eluting stent implantation, making these comparative effectiveness findings particularly relevant for clinical practice.
Study Limitations
The researchers acknowledged several limitations, including the open-label design where both patients and physicians knew which medication was assigned. Additionally, medication compliance was not assessed, and the study was conducted exclusively in India, potentially limiting generalizability to other healthcare systems and populations.
The medication comparison analysis followed patients for one year, while other components of the broader TUXEDO trial will continue for five years to assess longer-term outcomes.
