Differential Effects of Ticagrelor 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 heart disease but confers a bleeding risk. To compare the effects of ticagrelor-monotherapy with ticagrelor-based DAPT on hemostatic system activation, we conducted a randomized controlled trial in 44 volunteers using a loading-dose regimen and measured platelet-aggregometry triggered by adenosine diphosphate (multiple electrode aggregometry (MEA)-ADP) and arachidonic acid (MEA-AA), the vasodilator-stimulated phosphoprotein (VASP), prothrombin fragment 1.2 (f1.2), and d-Dimer. Ticagrelor-based DAPT and ticagrelor-monotherapy significantly decreased MEA-ADP (Δmean: -51.4 (-56.9; -45.8) and -46.2 (-51.7; -40.7)) and VASP (Δmean: -70.3 (-76.2; -64.4) and -69.6 (-75.5; -63.7)) at 2 hours and over 24 hours. MEA-AA was reduced significantly by both treatments (Δmean: -72.9 (-80.6; -65.3) and -25.7 (-33.3; -18.0)) at 2 hours, and stronger by ticagrelor-based DAPT over 24 hours. Both treatments decreased f1.2 (geometric mean ratio (GMR): 0.92 (0.84; 1.01) and 0.88 (0.80; 0.96)) and d-Dimer (GMR: 0.89 (0.86; 0.92) and 0.91 (0.88; 0.94)) at 2 hours and d-Dimer over 24 hours. Ticagrelor-monotherapy and ticagrelor-based DAPT comparably affect hemostatic system activation.

Figure 1

Boxplots of the effects of ticagrelor combined with aspirin and ticagrelor combined with placebo on adenosine diphosphate‐triggered platelet aggregation (multiple electrode aggregometry (MEA)‐ADP) (a), arachidonic acid‐triggered aggregation (MEA‐AA) (b), and vasodilator‐stimulated phosphoprotein (VASP) levels (c) in venous blood at different time points over the observation period compared with baseline levels. *P < 0.05 for changes from baseline to 2 hours, from baseline to 24 hours, from 2 to 24 hours, and between treatment groups. n.s., nonsignificant; PRI, platelet reactivity index; U, units.

Figure 2

Boxplot of the effects of ticagrelor combined with aspirin and ticagrelor combined with placebo on thromboxane B₂ (TxB₂) levels in venous blood at baseline and 24 hours after study treatment. *P < 0.05 for changes from baseline to 24 hours and between treatment groups. n.s., nonsignificant.

Figure 3

Boxplots of the effects of ticagrelor combined with aspirin and ticagrelor combined with placebo on prothrombin fragment 1.2 (f1.2) (a) and d‐Dimer (b) levels in venous blood at different time points over the observation period compared with baseline levels. *P < 0.05 for changes from baseline to 2 hours, from baseline to 24 hours, from 2 to 24 hours, and between treatment groups. n.s., nonsignificant.