De-escalation of antiplatelet therapy to evaluate platelet reactivity and clinical outcomes after coronary stenting in patients at high bleeding risk and recent acute coronary syndrome: Rationale and design of the DESC-HBR trial.
BACKGROUND Patients at high bleeding risk (HBR) presenting with acute coronary syndrome (ACS) and treated with percutaneous coronary intervention (PCI) have competing hazards of ischemic and bleeding events. In unselected ACS populations, trials of unguided de-escalation of P2Y12 inhibition reduce bleeding without excess ischemia; however, HBR patients were largely underrepresented in these studies. Comparative evidence across multiple de-escalation regimens in this vulnerable cohort is currently lacking. STUDY DESIGN DESC-HBR is a prospective, multicenter, randomized, open-label trial with blinded endpoint adjudication enrolling 200 HBR patients (PRECISE-DAPT ≥25 or ARC-HBR criteria) at 30 ± 7 days after ACS-PCI. Following one month of dual antiplatelet therapy (DAPT) with prasugrel 10 mg once daily or ticagrelor 90 mg twice daily, on a background of aspirin 100 mg, patients are randomized (1: 1:1:1) to clopidogrel 75 mg once daily, prasugrel 5 mg once daily, ticagrelor 60 mg twice daily, or continuation of full-dose potent therapy. The primary endpoint is the proportion of patients achieving optimal platelet reactivity (VerifyNow PRU 85-208) at 14 ± 2 days post-randomization, 2-h after maintenance dose. Key secondary outcomes include BARC bleeding, net adverse clinical events, quality of life and adherence. Pharmacodynamic profiling incorporates VerifyNow and Total Thrombus Formation Analysis (T-TAS). A total sample of 200 patients allows >80% power to detect superiority of each de-escalation arm versus control (α = 0.017). CONCLUSIONS DESC-HBR is the first randomized trial directly comparing multiple P2Y12 inhibitor de-escalation strategies in HBR patients post-ACS. By integrating pharmacodynamic, clinical, and patient-reported outcomes, it will provide information to guide individualized antiplatelet strategies balancing ischemic protection and bleeding mitigation in HBR patients. CLINICAL TRIAL REGISTRATION UNIQUE IDENTIFIER NCT05903976, EudraCT 2023-000029-10.