Guided De-escalation of Antiplatelet Treatment in Patients at High Atherothrombotic Risk Presenting With Acute Coronary Syndrome: A Post-Hoc Analysis of the TROPICAL-ACS trial

Background Platelet function testing (PFT)–guided de-escalation of dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS) has been shown to reduce bleeding risk without increasing ischemic events. Patients with high atherothrombotic risk (ATR) remain a challenging subgroup for such strategies. This study evaluated the safety and efficacy of early PFT-guided DAPT de-escalation according to ATR status. Methods In the TROPICAL-ACS trial, 2,610 ACS patients were randomized to standard 12-month prasugrel therapy or PFT-guided DAPT de-escalation. For this post hoc analysis, patients were stratified by ATR. High ATR was defined as age ≥65 years, polyvascular disease, or ≥2 risk factors (diabetes, smoking, or renal dysfunction). Hazard ratios (HR) for clinical endpoints were derived using multistate Cox regression. Results High-ATR patients (n=990) had a higher incidence of the primary net clinical benefit endpoint—composite of cardiovascular death, myocardial infarction, stroke, or BARC 2–5 bleeding—compared with low-ATR patients (n=1,620) (11.0% vs. 6.7%; HR 1.67, 95% CI 1.28–2.18; p<0.001). PFT-guided de-escalation showed no significant interaction by ATR status for the primary endpoint (high-ATR: 10.5% vs. 11.5%, HR 0.90 [0.61–1.32], p=0.586; low-ATR: 5.6% vs. 7.7%, HR 0.71 [0.48–1.04], p=0.082; p_interaction=0.394) or ischemic events (high-ATR: 3.7% vs. 4.4%, HR 0.83 [0.44–1.56]; low-ATR: 1.8% vs. 2.6%, HR 0.68 [0.35–1.34]; p_interaction=0.666). Conclusion Early PFT-guided de-escalation from prasugrel to clopidogrel was safe across atherothrombotic risk categories, supporting individualized DAPT optimization in ACS patients with both low and high ischemic risk.