Abstract

Abstract Aims To assess the feasibility of switching from dual antiplatelet therapy (DAPT) to dual pathway inhibition (DPI) and to compare the pharmacodynamic (PD) profiles of these treatment regimens. Methods and results This was a prospective, randomized, PD study conducted in 90 patients with chronic coronary syndrome (CCS) on DAPT with aspirin (81 mg/qd) plus a P2Y12 inhibitor [clopidogrel (75 mg/qd; n = 30), ticagrelor (90 mg/bid; n = 30), or prasugrel (10 mg/qd; n = 30)]. Patients in each cohort were randomized to maintain DAPT or switch to DPI (aspirin 81 mg/qd plus rivaroxaban 2.5 mg/bid). PD assessments included: VerifyNow P2Y12 reaction units; light transmittance aggregometry following stimuli with adenosine diphosphate (ADP), tissue factor, and a combination of collagen, ADP, and TF (CATF, maximum platelet aggregation %); thrombelastograph coagulation analyzer; thrombin generation (TG). Assays were performed at baseline (on DAPT) and 30 days post-randomization (trough and peak). Switching from DAPT to DPI occurred without major side effects. DAPT was associated with enhanced P2Y12 inhibition, while DPI with reduced TG. Platelet-mediated global thrombogenicity (primary endpoint) showed no differences between DAPT and DPI in the ticagrelor (14.5% [0.0–63.0] vs. 20.0% [0.0–70.0]; p = 0.477) and prasugrel (20.0% [0.0–66.0] vs. 4.0% [0.0–70.0]; p = 0.482), but not clopidogrel (27.0% [0.0–68.0] vs. 53.0% [0.0–81.0]; p = 0.011), cohorts. Conclusion In patients with CCS, switching from different DAPT regimens to DPI was feasible, showing enhanced P2Y12 inhibition with DAPT and reduced TG with DPI, with no differences in platelet-mediated global thrombogenicity between DPI and ticagrelor- and prasugrel, but not clopidogrel-, based DAPT.

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