Rationale: The interaction between nonvitamin K oral anticoagulants (NOACs) and platelet
aggregation is complex. The direct activated factor X inhibitors (factor Xa inhibitors) an
NOAC antagonizes thrombin generation, one of most important platelet agonist, so that, factor
Xa inhibitors has a potential effect in decreasing thrombin-mediated platelet aggregation. On
the other hand, patients who experience ACS continue to have a hypercoagulable state for long
periods after the index event. The COMPASS trial showed that, in patients with stable
coronary artery disease (SCAD), Rivaroxaban (a direct anti-Xa inhibitor) in addition to
antiplatelet agent, compared to antiplatelet therapy alone, reduced the composite endpoint of
myocardial infarction, stroke and death.
Objective: Analyze the role of edoxaban on platelet aggregation in SCAD patients.
Methods and Results: This is a prospective, non-randomized, interventional study of SCAD
patients taking low-dose acetylsalicylic acid (ASA). Subjects initially will receive in the
following sequence: ASA 100 mg once daily (QD) plus edoxaban 60 mg QD, clopidogrel 75 mg QD
alone, clopidogrel 75 mg QD plus edoxaban 60 mg QD, and edoxaban 60 mg QD alone. Platelet
function will be assessed by standard of care technology, at baseline and after each
intervention phase, by Multiplate-ADP® (primary endpoint), Multiplate-Aspi® and
Multiplate-TRAP®. In addition to immature platelets fraction (% IPF) and count (IPC).
Coagulability will be assessed, at baseline and after each intervention phase, by
thromboelastogram (TEG) assessment. Specifically, after the phases in which edoxaban will be
administered activated factor X (FXa) level and Plasminogen activator inhibitor-1 (PAI-1)
will be evaluated in addition to previous. Finally, inflammatory markers will be, at same
way, assessed at baseline and after intervention each phase: ultrasensitive C-reactive
protein (us-PCR).
Keywords: edoxaban, direct factor Xa inhibitor, stable coronary artery disease, aspirin,
clopidogrel, platelet aggregation.