Ticagrelor With or Without Aspirin in High-Risk Patients After PCI in the TWILIGHT Trial

Background: An evolving strategy in the setting of percutaneous coronary intervention (PCI) involves withdrawal of acetylsalicylic acid (ASA), or aspirin, while maintaining P2Y₁₂ inhibition. However, the pharmacodynamic effects of this approach on blood thrombogenicity and platelet reactivity remain unknown. Objectives: This study sought to compare the antithrombotic potency of ticagrelor alone versus ticagrelor plus ASA among high-risk patients undergoing PCI with drug-eluting stents. Methods: This was a mechanistic substudy within the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial, which randomized patients undergoing PCI to ticagrelor plus placebo versus ticagrelor plus ASA following 3 months of dual antiplatelet therapy. Substudy participants were enrolled after randomization, at which time ex vivo assays to quantify thrombus size under dynamic flow conditions and platelet reactivity were performed. Pharmacodynamic assessments were repeated 1 to 6 months thereafter. The primary endpoint was thrombus size at the post-randomization visit with platelet reactivity following stimuli to arachidonic acid, collagen, adenosine diphosphate, and thrombin as secondary endpoints. Results were analyzed using analysis of covariance. Results: A total of 51 patients were enrolled, among whom 42 underwent perfusion assays at baseline and follow-up with a median time between studies of 1.5 months. The adjusted mean difference in post-randomization thrombus area was similar between groups: −218.2 μm² (95% confidence interval [CI]: −575.9 to 139.9 μm²; p = 0.22). Markers sensitive to cyclo-oxygenase-1 blockade, including platelet reactivity in response to arachidonic acid (mean difference: 10.9 U; 95% CI: 1.9 to 19.9 U) and collagen (mean difference: 9.8 U; 95% CI: 0.8 to 18.8 U) stimuli were higher among patients receiving placebo, whereas levels of platelet reactivity were similar with adenosine diphosphate and thrombin. Conclusions: Among high-risk patients receiving drug-eluting stents, the antithrombotic potency of ticagrelor monotherapy is similar to that of ticagrelor plus ASA with respect to ex vivo blood thrombogenicity, whereas markers sensitive to cyclo-oxygenase-1 blockade are increased in the absence of ASA. (Platelet Substudy of the TWILIGHT Trial; NCT04001374).