No difference in ex vivo thrombogenicity with ticagrelor monotherapy vs. DAPT
Ticagrelor With or Without Aspirin After PCI- The TWILIGHT Platelet Substudy
Introduction and methods
Short duration of dual antiplatelet therapy (DAPT) followed by withdrawal of aspirin and maintaining a P2Y12 inhibitor is a potential therapeutic approach to reduce bleeding risk while preserving ischemic benefit in patients after PCI . This approach was tested in the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial and showed that ticagrelor
Monotherapy reduced clinically relevant bleeding without increasing ischemic events in high-risk patients undergoing PCI with drug-eluting stents .
This pharmacodynamic substudy of TWILIGHT examined the effect of ticagrelor monotherapy vs. ticagrelor plus aspirin on blood thrombogenicity and platelet reactivity.
TWILIGHT was a randomized, double-blind, placebo-controlled trial enrolling high-risk patients undergoing PCI, who received aspirin and ticagrelor after discharge . After 3 months of DAPT, patients were randomized in a 1:1 ratio to aspirin plus ticagrelor or placebo plus ticagrelor. This substudy was performed at a single site (Mount Sinai Hospital, New York, NY, USA) and enrolled 51 patients (23 randomized to ticagrelor monotherapy and 28 to DAPT). The primary outcome was blood thrombogenicity, measured as the area of thrombus formed under high-shear dynamic flow conditions over porcine aorta in an ex vivo Badimon perfusion chamber [3-6]. Platelet reactivity was measured in whole blood by impedance aggregometry using the Multiplate Analyzer, in response to platelet agonists adenosine diphosphate (ADP), thrombin, and cyclo-oxygenase (COX-1) (which is blocked by aspirin) arachidonic acid (AA) and collagen. Thrombogenicity and platelet reactivity were measured immediately after randomization (baseline) and after 1 to 6 months after randomization (median time between assessments was 41 days, IQR: 31-61 days).
- For most patients, thrombus area was not changed between baseline and follow up visit, irrespective of the treatment group. Mean difference in thrombus area between baseline and follow-up was 21.6 mm² (95% CI: 261.9 to 305.3 mm²) in those receiving ticagrelor monotherapy and in patients receiving DAPT this was 162.3 mm² (95% CI: 71.3 to 395.8 mm²).
- There was no difference in post-randomization thrombus size between groups (adjusted mean difference: 218.2 mm², 95% CI: 575.9 to 139.9 mm², P=0.22).
- Difference between the 2 groups for ADP and thrombin-induced aggregation were -2.2 U (95% CI: -8.2 to 3.8 U) and 0.96 U (95% CI: -7.1 to 8.9 U), respectively. Platelet reactivity with COX-1 sensitive agonists AA and collagen were higher in patients receiving monotherapy compared to patients receiving DAPT (adjusted mean difference with AA: 10.9 U; 95% CI: 1.9 to 19.9 U, P=0.02 and with collagen: 9.8 U; 95% CI: 0.82 to 18.8 U, P=0.03).
This substudy of the TWILIGHT trial showed that there was no difference in thrombogenicity between patients treated with ticagrelor monotherapy and those treated with DAPT. Platelet reactivity, measured by aggregometry, in response to ADP or thrombin were similar between groups, but was different between those on ticagrelor monotherapy and those on DAPT in response to agonists sensitive to COX-1.