Effects of clopidogrel with or without aspirin on the generation of extracellular vesicles in the microcirculation and in venous blood: A randomized placebo controlled trial

Background: Dual-antiplatelet therapy (DAPT) is a standard strategy in acute coronary heart disease; however, it confers a considerable bleeding risk. Single-antiplatelet therapy (SAPT) inhibits haemostatic system activation ex vivo to a similar extent as DAPT. Extracellular vesicles (EV) are procoagulant and contribute to haemostatic system activation. We aimed to investigate the effect of DAPT compared with SAPT on EV. Methods: In a randomized, double-blind, placebo-controlled trial, 44 healthy volunteers received DAPT (clopidogrel+aspirin) or SAPT (clopidogrel+placebo) for 7 days. Blood was obtained from a standardized microvascular injury and through venipuncture at baseline (BL) and at 2 h, 24 h, and 8 days after treatment initiation. The number, origin, and surface expression of EV were assessed using flow cytometry. Data are given as median (quartiles). Non-parametric tests were used to evaluate the short-term (BL vs 2 h) and long-term differences (2 h to 8 days), as well as the differences between treatment groups. Results: There was no difference either in the short-term effects on the number (x 10(3) mL(-1)) of EV in microvascular blood between DAPT [BL: 1433 (653; 3184) vs 2 h: 862 (545; 2026), p=0.39] and SAPT [(BL: 614 (552; 1402) vs 2 h: 1079 (781; 1538), p=0.75)] or in the long-term effects. DAPT and SAPT did not exhibit differential short-term effects on the number and proportion (36% and 27% vs 55% and 36%) of platelet-derived EV. DAPT and SAPT resulted in a significant short-term increase in phosphatidylserine expression in microvascular blood. The effects of DAPT and SAPT on EV in venous blood were similar to those in microvascular blood. Conclusion: DAPT and SAPT have comparable effects on the amount, origin, and surface characteristics of EV.