Breaking Down the TUXEDO-2 Findings: Antithrombotic Choices After PCI

TUXEDO-2 shows prasugrel reduced one‑year ischemic events and major bleeding compared with ticagrelor in patients with diabetes undergoing drug‑eluting stent placement — a finding that should influence P2Y12 selection for high‑risk diabetic PCI patients.

In a randomized head‑to‑head comparison, the TUXEDO-2 trial enrolled roughly 1,800 adults with diabetes and predominantly multivessel coronary disease who underwent drug‑eluting stent placement and were randomized to one year of dual antiplatelet therapy with aspirin plus ticagrelor or prasugrel.

The research notes key inclusion elements (about 25% insulin‑treated) and reports both an ischemic composite (myocardial infarction, stroke, and death) and a separate major‑bleeding safety analysis.

For efficacy, the findings report a lower primary composite event rate with prasugrel (14.23%) than with ticagrelor (16.57%) — an absolute difference of 2.34 percentage points (≈14% relative reduction). Nonfatal MI occurred in 5.21% versus 5.96% and all‑cause death was 3.67% versus 5.03% for prasugrel versus ticagrelor, respectively. Stent thrombosis and other ischemic components were included in the one‑year composite.

On safety, major bleeding was reported less often with prasugrel (7.14%) than with ticagrelor (8.41%), and there was not a clear excess of intracranial or fatal bleeding for either agent at one year. Dyspnea and adherence were not emphasized as major drivers. The trial’s net clinical‑benefit metric, combining ischemic events and major bleeding, favored prasugrel — indicating the ischemic advantage outweighed the small absolute bleeding difference in this cohort.

Historically, prasugrel and ticagrelor have often been treated as interchangeable potent P2Y12 inhibitors. TUXEDO‑2 challenges that assumption for patients with diabetes undergoing PCI by demonstrating measurable outcome differences. Because the comparison used one‑year DAPT, the results support attention to at least a one‑year strategy in similar high‑risk cohorts but do not by themselves mandate routine DAPT shortening. Individualized DAPT duration should still be guided by ischemic and bleeding risk, procedural factors, and patient preferences.

Key Takeaways:

• In this randomized cohort of ~1,800 diabetic patients after drug‑eluting stent placement, prasugrel was associated with lower one‑year composite events (14.23% vs 16.57%) and fewer major bleeds (7.14% vs 8.41%).
• The absolute benefits with prasugrel were modest but directionally consistent across ischemic and bleeding measures, supporting non‑equivalence of these two P2Y12 inhibitors in this population.
• Practice impact centers on P2Y12 agent choice and individualized DAPT planning for high‑risk diabetic PCI patients while awaiting replication and formal guideline consideration.