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

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: 600 mg, d2‐6: 150 mg) ± aspirin (100 mg)). 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 2 hours (−60% vs. −63%; P = 0.35, Δmean −4.9, 95% CI −15.4 to 5.5). At 24 hours (−59% vs. −47%, P = 0.04, Δmean −11.1, 95% CI −21.7 to −0.4]) and 8 days (−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 2 hours and 8 days. DAPT inhibited MEA‐AA significantly stronger at 2 hours (−77% vs. −30%; P < 0.0001, Δmean −39.6, 95% CI −54.2 to −25.0), at 24 hours (−80% vs. −27%, P < 0.0001, Δmean −47.8, 95% CI −62.3 to −33.3), and 8 days (−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 24 hours and 8 days. The d‐Dimer was reduced by DAPT (0.94, 95% CI 0.89–1.00, P = 0.04) at 2 hours but not after 24 hours 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.