Safety and efficacy of edoxaban monotherapy after bioabsorbable polymer everolimus-eluting stent implantation in a human-like coronary atherosclerotic porcine model
Background: 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 impl...
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Elsevier
2025-03-01
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| Series: | Atherosclerosis Plus |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667089525000021 |
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| author | Daisuke Kitano Suguru Migita Yuxin Li Yutaka Koyama Katsunori Fukumoto Sayaka Shimodai-Yamada Akira Onishi Daiichiro Fuchimoto Shunichi Suzuki Yoshiyuki Nakamura Atsushi Hirayama Hiroyuki Hao Yasuo Okumura |
| author_facet | Daisuke Kitano Suguru Migita Yuxin Li Yutaka Koyama Katsunori Fukumoto Sayaka Shimodai-Yamada Akira Onishi Daiichiro Fuchimoto Shunichi Suzuki Yoshiyuki Nakamura Atsushi Hirayama Hiroyuki Hao Yasuo Okumura |
| author_sort | Daisuke Kitano |
| collection | DOAJ |
| description | Background: 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). Methods: 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. Results: 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. Conclusions: 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. |
| format | Article |
| id | doaj-art-10c626ee291a436591a7c36b17202eae |
| institution | Kabale University |
| issn | 2667-0895 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Atherosclerosis Plus |
| spelling | doaj-art-10c626ee291a436591a7c36b17202eae2025-02-07T04:48:29ZengElsevierAtherosclerosis Plus2667-08952025-03-01595967Safety and efficacy of edoxaban monotherapy after bioabsorbable polymer everolimus-eluting stent implantation in a human-like coronary atherosclerotic porcine modelDaisuke Kitano0Suguru Migita1Yuxin Li2Yutaka Koyama3Katsunori Fukumoto4Sayaka Shimodai-Yamada5Akira Onishi6Daiichiro Fuchimoto7Shunichi Suzuki8Yoshiyuki Nakamura9Atsushi Hirayama10Hiroyuki Hao11Yasuo Okumura12Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan; Division of Advanced Cardiovascular Imaging, Department of Medicine, Nihon University School of Medicine, Tokyo, JapanDivision of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan; Division of Human Pathology, Department of Pathology and Microbiology, Nihon University, Tokyo, JapanDivision of Advanced Cardiovascular Imaging, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan; Division of Cell Regeneration and Transplantation, Department of Functional Morphology, Nihon University School of Medicine, Tokyo, Japan; Corresponding author. Division of Cell Regeneration and Transplantation, Department of Functional Morphology, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan.Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan; Division of Human Pathology, Department of Pathology and Microbiology, Nihon University, Tokyo, JapanDivision of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, JapanDivision of Human Pathology, Department of Pathology and Microbiology, Nihon University, Tokyo, JapanDivision of Cell Regeneration and Transplantation, Department of Functional Morphology, Nihon University School of Medicine, Tokyo, Japan; Department of Animal Science and Resources, College of Bioresource Sciences, Nihon University, Fujisawa, JapanInstitute of Agrobiological Sciences, National Agriculture and Food Research Organization (NARO), Tsukuba, JapanInstitute of Agrobiological Sciences, National Agriculture and Food Research Organization (NARO), Tsukuba, JapanAgricultural Technology Research Center, Swine and Poultry Research, Saitama, JapanDivision of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan; Cardiovascular Division, Osaka Police Hospital, Osaka, Japan; Internal Medicine, Osaka Fukujyuji Hospital, Osaka, JapanDivision of Human Pathology, Department of Pathology and Microbiology, Nihon University, Tokyo, JapanDivision of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan; Corresponding author.Background: 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). Methods: 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. Results: 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. Conclusions: 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.http://www.sciencedirect.com/science/article/pii/S2667089525000021Atrial fibrillationEdoxabanDrug-eluting stentPorcine modelOptical coherence tomographyHistology |
| spellingShingle | Daisuke Kitano Suguru Migita Yuxin Li Yutaka Koyama Katsunori Fukumoto Sayaka Shimodai-Yamada Akira Onishi Daiichiro Fuchimoto Shunichi Suzuki Yoshiyuki Nakamura Atsushi Hirayama Hiroyuki Hao Yasuo Okumura Safety and efficacy of edoxaban monotherapy after bioabsorbable polymer everolimus-eluting stent implantation in a human-like coronary atherosclerotic porcine model Atherosclerosis Plus Atrial fibrillation Edoxaban Drug-eluting stent Porcine model Optical coherence tomography Histology |
| title | Safety and efficacy of edoxaban monotherapy after bioabsorbable polymer everolimus-eluting stent implantation in a human-like coronary atherosclerotic porcine model |
| title_full | Safety and efficacy of edoxaban monotherapy after bioabsorbable polymer everolimus-eluting stent implantation in a human-like coronary atherosclerotic porcine model |
| title_fullStr | Safety and efficacy of edoxaban monotherapy after bioabsorbable polymer everolimus-eluting stent implantation in a human-like coronary atherosclerotic porcine model |
| title_full_unstemmed | Safety and efficacy of edoxaban monotherapy after bioabsorbable polymer everolimus-eluting stent implantation in a human-like coronary atherosclerotic porcine model |
| title_short | Safety and efficacy of edoxaban monotherapy after bioabsorbable polymer everolimus-eluting stent implantation in a human-like coronary atherosclerotic porcine model |
| title_sort | safety and efficacy of edoxaban monotherapy after bioabsorbable polymer everolimus eluting stent implantation in a human like coronary atherosclerotic porcine model |
| topic | Atrial fibrillation Edoxaban Drug-eluting stent Porcine model Optical coherence tomography Histology |
| url | http://www.sciencedirect.com/science/article/pii/S2667089525000021 |
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