Differential Effects of Clopidogrel with or without Aspirin on Platelet Reactivity and Coagulation Activation: a randomized trial in healthy volunteers.

Traby, Ludwig; Kollars, Marietta; Kaider Mag, Alexandra; Maria Siller-Matula, Jolanta; Steinbrecher, Oskar; Wolzt, Michael; Kyrle, Paul Alexander; Eichinger, Sabine

Dual antiplatelet therapy (DAPT) is standard in acute coronary syndrome but confers a bleeding risk. To compare effects of clopidogrel single antiplatelet therapy (SAPT) with clopidogrel-based DAPT on hemostatic system activation we conducted a RCT in 44 volunteers (clopidogrel [d1: 600mg, d2-6: 150 mg] +/- aspirin [100mg]). Adenosine diphosphate (MEA-ADP) and arachidonic acid (MEA-AA) triggered aggregometry, vasodilator-stimulated phosphoprotein (VASP), beta thromboglobulin, p-selectin, thromboxane B2 , d-Dimer, prothrombin fragment 1.2 (f1.2), and a phospholipid dependent clotting time (PPL) were measured in venous blood. Changes are described by mean differences (Δmean [95% CI]) or geometric mean ratios (GMR [95% CI]). DAPT and SAPT comparably and significantly decreased MEA-ADP at 2h (-60% vs -63%; p=0.35, Δmean -4.9 [-15.4; 5.5]). At 24h (-59% vs -47%, p=0.04, Δmean -11.1 [-21.7; -0.4]) and 8 days (-61% vs -53%, p=0.04, Δmean -11.3 [-22.0; -0.6]). Both treatments significantly reduced VASP and MEA-AA after 2h and 8 days. DAPT inhibited MEA-AA significantly stronger at 2h (-77% vs -30%; p<0.0001, Δmean -39.6 [-54.2; -25.0]), at 24h (-80% vs -27%, p<0.0001, Δmean -47.8 [-62.3; -33.3]), and 8 days (-79% vs -27%, p<0.0001, Δmean -48.9 [-62.5; -35.4]). Neither treatment significantly influenced beta thromboglobulin or p-selectin. DAPT abolished, and SAPT significantly reduced thromboxane B2 after 24h and 8 days. d-Dimer was reduced by DAPT (0.94 [0.89; 1.00], p=0.04) at 2h but not after 24h and 8 days. SAPT did not decrease d-Dimer. Neither treatment affected f1.2. DAPT and SAPT comparably affect platelet and coagulation activation in venous blood.