Effects of Edoxaban on Platelet Aggregation

Summary

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.

Conditions

• SCAD
• AMI

Interventions

DRUG

ASA

During the intervention phases, eligible patients will sequentially receive ASA 100 mg 1x/day + edoxaban 60 mg 1x/day for a period of 10 ± 2 days. Subsequently, ASA and edoxaban will be suspended and clopidogrel 75 mg once a day will be administered for 10 ± 2 days (washout period of the ASA). Subsequently, it will be associated with edoxaban 60 mg once a day to clopidogrel 75 mg once a day for 10 ± 2 days and, finally, only edoxaban 60 mg once a day for 10 ± 2 days will be administered. After the end of the interventions, the ASA 100 mg once a day will be restarted.

DRUG

Clopidogrel

During the intervention phases, eligible patients will sequentially receive ASA 100 mg 1x/day + edoxaban 60 mg 1x/day for a period of 10 ± 2 days. Subsequently, ASA and edoxaban will be suspended and clopidogrel 75 mg once a day will be administered for 10 ± 2 days (washout period of the ASA). Subsequently, it will be associated with edoxaban 60 mg once a day to clopidogrel 75 mg once a day for 10 ± 2 days and, finally, only edoxaban 60 mg once a day for 10 ± 2 days will be administered. After the end of the interventions, the ASA 100 mg once a day will be restarted.

DRUG

Edoxaban

During the intervention phases, eligible patients will sequentially receive ASA 100 mg 1x/day + edoxaban 60 mg 1x/day for a period of 10 ± 2 days. Subsequently, ASA and edoxaban will be suspended and clopidogrel 75 mg once a day will be administered for 10 ± 2 days (washout period of the ASA). Subsequently, it will be associated with edoxaban 60 mg once a day to clopidogrel 75 mg once a day for 10 ± 2 days and, finally, only edoxaban 60 mg once a day for 10 ± 2 days will be administered. After the end of the interventions, the ASA 100 mg once a day will be restarted.

Sponsors & Collaborators

• Daiichi Sankyo

  collaborator INDUSTRY

• University of Sao Paulo

  lead OTHER

Study Design

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-09-14

Primary Completion

2024-06-24

Completion

2024-06-24

Countries

• Brazil

Study Locations