Efficacy of Factor Xa Anticoagulant Monotherapy after Drug-Eluting Stent Implantation in a Human-Like Coronary Atherosclerotic Porcine Model
| Project/Area Number |
19K16621
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49030:Experimental pathology-related
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| Research Institution | Nihon University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 直接作用型経口抗凝固薬 / 薬剤溶出性ステント / 冠動脈狭窄症 / 大動物モデル / 血管内イメージング / 抗血栓療法 / 循環器内科学 / 動脈硬化 / 経口抗凝固薬 / ステント血栓 / 抗血小板薬 / 直接作用型第Xa因子阻害経口抗凝固薬 / DAPT / 冠動脈不安定粥腫モデル / LDL受容体ホモ欠損ブタ / 心房細動 |
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| Outline of Research at the Start |
冠動脈病変に対し、薬剤溶出性ステント（DES）を用いた冠動脈形成術が広く行われている。DES留置後の抗血小板薬と抗凝固薬の最適な組み合わせと投与期間については未だ明らかではない。本申請研究では、申請者らのグループが開発したLDLコレステロール受容体ホモ欠損ブタ動脈硬化モデルを用いて、冠動脈の不安定粥腫病変にDESを留置し、直接作用型第Xa因子阻害抗凝固薬および抗血小板薬投与下に経時的にステント内血栓形成および炎症反応と新規動脈硬化の進展を観察する。DES留置後のステント血栓形成の機序と影響因子を明らかにすることで、未解決である抗血小板薬と抗凝固薬の最適な組み合わせと至適投与期間の提案に繋がる。
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| Outline of Final Research Achievements |
Background: We evaluated the safety and efficacy of factor Xa inhibitor, edoxaban monotherapy in a low-density lipoprotein receptor knockout (LDLR-/-) miniature pig with human-like unstable coronary plaques compared to conventional dual-antiplatelet therapy (DAPT).
Methods & results: Drug-eluting stents (DES) were implanted in LDLR-/- pigs with unstable coronary plaque. The pigs were given a DAPT comprising of aspirin and clopidogrel or an edoxaban orally 3 days before DES implantation and then daily throughout the follow-up period. One month after DES implantation, optical coherence tomography assessment showed the neointima in the edoxaban was thinner than that in the DAPT. Histological analysis revealed fibrin deposits and inflammatory cells infiltration in the peri-strut region were similar in both groups. No instent thrombi were observed.
Conclusion: Our results showed that the edoxaban monotherapy was non-inferior to DAPT after DES implantation in terms of safety and efficacy.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒトに類似した大動物モデルを用いた本研究の成果は、薬剤溶出性ステント留置時から直性作用型経口抗凝固薬単剤でも安全性に寄与するだけでなく、ステント再狭窄の抑制に繋がる可能があり、今後実臨床においてより少ない抗血栓薬の投与で十分な冠動脈ステント留置治療を行うことができることを支持するという重要な意義を持つ。
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Report
(4 results)
Research Products
(4 results)
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[Presentation] Safety and Efficacy of Edoxaban Monotherapy after Bioabsorbable Polymer Everolimus-Eluting Stent Implantation in a Human-like Coronary Atherosclerotic Porcine Model2022
Author(s)
Daisuke Kitano, Yuxin Li, Suguru Migita, Yutaka Koyama, Akira Onishi, Daiichiro Fuchimoto, Shunichi Suzuki, Yoshiyuki Nakamura, Atsushi Hirayama, Hiroyuki Hao, Yasuo Okumura
Organizer
第86回日本循環器学会学術集会
Related Report
Int'l Joint Research
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[Presentation] Safety and Efficacy of Edoxaban Monotherapy after Bioabsorbable Polymer Everolimus-Eluting Stent Implantation in a Human-like Coronary Atherosclerotic Porcine Model2022
Author(s)
Daisuke Kitano, Yuxin Li, Suguru Migita, Yutaka Koyama, Akira Onishi, Daiichiro Fuchimoto, Shunichi Suzuki, Yoshiyuki Nakamura, Atsushi Hirayama, Hiroyuki Hao, Yasuo Okumura
Organizer
ACC 22
Related Report
Int'l Joint Research
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