# Safety and efficacy of edoxaban monotherapy after bioabsorbable polymer everolimus-eluting stent implantation in a human-like coronary atherosclerotic porcine model

## TL;DR

The study finds that edoxaban monotherapy is as safe and more effective than standard antiplatelet therapy after stent implantation in a pig model with human-like coronary disease.

## Contribution

This is the first preclinical evaluation of DOAC monotherapy safety and efficacy in a human-like coronary plaque model after drug-eluting stent implantation.

## Key findings

- Edoxaban monotherapy significantly reduced neointimal thickness and area compared to dual antiplatelet therapy.
- Edoxaban suppressed lipidic and necrotic plaque growth while promoting fibrotic plaque stabilization.
- No in-stent thrombi were observed in either treatment group, indicating equivalent safety.

## Abstract

The combination of antiplatelet and antithrombotic drugs increases the risk of bleeding in patients with atrial fibrillation after coronary drug-eluting stent (DES) implantation. However, the appropriateness of direct-acting oral anticoagulant (DOAC) monotherapy at the time of stent implantation remains uncertain. The objective of this study was to evaluate the safety and efficacy of DOAC monotherapy, specifically using factor Xa inhibitors such as edoxaban, in a low-density lipoprotein receptor knockout (LDL-R−/−) miniature pig model of human-like unstable coronary plaques compared to conventional dual-antiplatelet therapy (DAPT).

We evaluated the safety and efficacy of edoxaban monotherapy in the LDL-R−/− pig model with human-like unstable coronary plaques induced by a high-cholesterol, high-fat diet. Animals underwent DES implantation, followed by four weeks of treatment with either edoxaban monotherapy (3 mg/kg/day) or the DAPT regimen (aspirin 100 mg/day and clopidogrel 75 mg/day). Outcomes were assessed by optical coherence tomography (OCT), virtual histology intravascular ultrasound (iMap-IVUS), and histology. Key endpoints included in-stent thrombus formation, neointimal thickness, and coronary plaque composition.

Edoxaban monotherapy demonstrated a significantly thinner neointimal layer (120.0 [92.5–160.0] μm vs. 210.0 [180.0–240.0] μm, p < 0.001) and smaller neointimal area (1.06 [0.82–1.46] mm2 vs. 1.84 [1.61–2.24] mm2, p < 0.001) compared to DAPT. Neointimal coverage, fibrin deposition, and inflammatory cell infiltration were comparable between groups. No in-stent thrombi were observed in either group. iMap-IVUS findings indicated that edoxaban monotherapy significantly suppressed the increase in lipidic and necrotic plaque area while promoting fibrotic area expansion.

Edoxaban monotherapy demonstrated superior efficacy in suppressing neointimal hyperplasia and stabilizing coronary plaques compared to DAPT with equivalent safety in preventing in-stent thrombus formation. These results provide important preclinical evidence supporting the potential of DOAC monotherapy as an antithrombotic strategy after DES implantation and warrant further investigation in clinical trials.

•Enhancing the relevance of translational research to simulate human coronary artery responses using a human-like coronary artery plaque porcine model.•Equivalent safety of edoxaban monotherapy versus DAPT in preventing in-stent thrombus formation.•Greater efficacy of edoxaban monotherapy compared to DAPT in reducing in-stent neointimal hyperplasia and stabilizing coronary artery plaque.

Enhancing the relevance of translational research to simulate human coronary artery responses using a human-like coronary artery plaque porcine model.

Equivalent safety of edoxaban monotherapy versus DAPT in preventing in-stent thrombus formation.

Greater efficacy of edoxaban monotherapy compared to DAPT in reducing in-stent neointimal hyperplasia and stabilizing coronary artery plaque.