Differential Effects of Clopidogrel With or Without Aspirin on Platelet Reactivity and Coagulation Activation: A Randomized Trial in Healthy Volunteers

Abstract

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 randomized clinical trial in 44 volunteers (clopidogrel (d1: 600mg, d2-6: 150mg) ± aspirin (100mg)). Multiple electrode aggregometry-adenosine diphosphate (MEA-ADP) and MEA-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 were measured in venous blood. Changes are described by mean differences (Δmean (95% confidence interval (CI)) or geometric mean ratios (95% CI)). DAPT and SAPT comparably and significantly decreased MEA-ADP at 2hours (-60% vs. -63%; P=0.35, Δmean -4.9, 95% CI -15.4 to 5.5). At 24hours (-59% vs. -47%, P=0.04, Δmean -11.1, 95% CI -21.7 to -0.4]) and 8days (-61% vs. -53%, P=0.04, Δmean -11.3, 95% CI -22.0 to -0.6). Both treatments significantly reduced VASP and MEA-AA after 2hours and 8days. DAPT inhibited MEA-AA significantly stronger at 2hours (-77% vs. -30%; P<0.0001, Δmean -39.6, 95% CI -54.2 to -25.0), at 24hours (-80% vs. -27%, P<0.0001, Δmean -47.8, 95% CI -62.3 to -33.3), and 8days (-79% vs. -27%, P<0.0001, Δmean -48.9, 95% CI -62.5 to -35.4). Neither treatment significantly influenced beta thromboglobulin or p-selectin. DAPT abolished and SAPT reduced thromboxane B2 after 24hours and 8days. The d-Dimer was reduced by DAPT (0.94, 95% CI 0.89-1.00, P=0.04) at 2hours but not after 24hours and 8days. SAPT did not decrease d-Dimer. Neither treatment affected f1.2. DAPT and SAPT comparably affect platelet and coagulation activation in venous blood.