Comparison of antithrombotic and haemorrhagic effects of edoxaban, an oral direct factor Xa inhibitor, with warfarin and enoxaparin in rats

Morishima, Yasuo; Honda, Yuko; Kamisato, Chikako; Tsuji, Naoki; Kita, Akemi; Edo, Naoko; Shibano, Toshiro

doi:10.1016/j.thromres.2012.05.008

Cited by 23 publications

(11 citation statements)

References 13 publications

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“…A study conducted in Japan for preventing thromboembolic events following orthopaedic surgery demonstrated that edoxaban was superior to enoxaparin for preventing DVT [13]. Another study found that edoxaban inhibited DVT comparably with warfarin and enoxaparin in rats [14]. The results of our study support these studies.…”

Section: Resultssupporting

confidence: 83%

“…in efficacy and comparable regarding the incidence of bleeding [11]. Another study concluded that edoxaban inhibited DVT comparably to warfarin and enoxaparin, and the attendant bleeding risk of edoxaban was lower than that of warfarin and enoxaparin in rats [14]. Thus, it appears that the safety margin of edoxaban is greater than that of enoxaparin.…”

Section: Resultsmentioning

confidence: 99%

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Retrospective comparison of three thromboprophylaxis agents, edoxaban, fondaparinux, and enoxaparin, for preventing venous thromboembolism in total knee arthroplasty

Sasaki

Ishida

Shibanuma

et al. 2013

International Orthopaedics (SICOT)

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Purpose Patients undergoing total knee arthroplasty (TKA) are at high risk of venous thromboembolism, manifesting as deep vein thrombosis (DVT) or pulmonary embolism. The purpose of this study is to evaluate the efficacy and safety of edoxaban 15 mg once daily (o.d.) for preventing DVT in patients undergoing TKA. Methods Three hundred patients undergoing primary TKA under general anaesthesia for osteoarthritis were enrolled in this study: 100 treated with enoxaparin 2,000 IU twice daily (b.i.d.), 100 treated with fondaparinux 1.5 mg o.d. and 100 treated with edoxaban 15 mg o.d.. All treatments were scheduled to continue for 14 days. Results The incidence of DVT in patients treated with edoxaban 15 mg o.d. was lower than in patients with enoxaparin 2,000 IU b.i.d. and fondaparinux 1.5 mg o.d.. Ddimer levels were significantly lower in patients with edoxaban than in patients with enoxaparin and fondaparinux 1.5 mg o.d. on the first postoperative day; ΔHb levels were lower in patients with edoxaban than in patients with enoxaparin and fondaparinux on postoperative days, However, the difference was not statistically significant. Finally, the incidence of hepatic dysfunction was lower in patients with edoxaban than in patients with enoxaparin and fondaparinux. Conclusions Edoxaban 15 mg o.d. was more efficient than enoxaparin 2,000 IU b.i.d. and fondaparinux 1.5 mg o.d.. Furthermore, edoxaban was safe compared with enoxaparin and fondaparinux. Edoxaban, an orally administered direct factor Xa (FXa) inhibitor, may offer a new option for preventing DVT, with a level of evidence III.

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Section: Resultssupporting

confidence: 83%

Section: Resultsmentioning

confidence: 99%

Retrospective comparison of three thromboprophylaxis agents, edoxaban, fondaparinux, and enoxaparin, for preventing venous thromboembolism in total knee arthroplasty

Sasaki

Ishida

Shibanuma

et al. 2013

International Orthopaedics (SICOT)

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“…The effective doses of edoxaban for preventing stent thrombosis (1 and 3 mg/kg) were similar to those for venous thrombosis in rats [16]. Edoxaban is approved for the prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation [14].…”

Section: Discussionmentioning

confidence: 99%

Prevention of Stent Thrombosis in Rats by a Direct Oral Factor Xa Inhibitor Edoxaban

2018

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Background/Aims: Stent thrombosis is a serious complication after percutaneous coronary intervention and femoropopliteal endovascular intervention. The aim of this study was to determine the antithrombotic effects of a direct factor Xa inhibitor edoxaban alone or in combination with antiplatelet agents in a rat model of stent thrombosis. Methods: Stainless steel stents (4 stents per rat) were placed in an extracorporeal arteriovenous shunt. The shunt was inserted into the carotid artery and the jugular vein in each rat to circulate blood. Stent thrombosis was induced by exposing the stents to arterial blood for 30 min. Protein content of the thrombus was measured. Edoxaban and antiplatelet agents (aspirin, clopidogrel, and ticagrelor) were orally administered before the thrombus induction. Results: Edoxaban (0.3–3 mg/kg), clopidogrel (1–10 mg/kg), aspirin (10–100 mg/kg), and ticagrelor (0.3–3 mg/kg) exerted significant and dose-dependent antithrombotic effects in a rat stent thrombosis model. The effect of edoxaban was comparable to that of antiplatelet agents. The combination of submaximal doses of edoxaban and clopidogrel or aspirin significantly potentiated the antithrombotic effects compared with antiplatelet agents alone. Conclusion: These results suggest that edoxaban alone and in combination with clopidogrel or aspirin are promising antithrombotic therapies for the prevention of stent thrombosis.

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“…In animal models, edoxaban inhibited venous thrombosis to an extent comparable with that of warfarin and enoxaparin, and the bleeding tendency was low 78. Edoxaban is rapidly absorbed following oral administration, with a time to peak plasma concentrations of 1–2 hours 79.…”

Section: Edoxabanmentioning

confidence: 99%

Potential role of new anticoagulants for prevention and treatment of venous thromboembolism in cancer patients

Gómez-Outes¹,

Ml²,

Ai³

et al. 2013

VHRM

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Venous thromboembolism (VTE), encompassing deep vein thrombosis and pulmonary embolism, represents a major cause of morbidity and mortality in patients with cancer. Low molecular weight heparins are the preferred option for anticoagulation in cancer patients according to current clinical practice guidelines. Fondaparinux may also have a place in prevention of VTE in hospitalized cancer patients with additional risk factors and for initial treatment of VTE. Although low molecular weight heparins and fondaparinux are effective and safe, they require daily subcutaneous administration, which may be problematic for many patients, particularly if long-term treatment is needed. Studying anticoagulant therapy in oncology patients is challenging because this patient group has an increased risk of VTE and bleeding during anticoagulant therapy compared with the population without cancer. Risk factors for increased VTE and bleeding risk in these patients include concomitant treatments (surgery, chemotherapy, placement of central venous catheters, radiotherapy, hormonal therapy, angiogenesis inhibitors, antiplatelet drugs), supportive therapies (ie, steroids, blood transfusion, white blood cell growth factors, and erythropoiesis-stimulating agents), and tumor-related factors (local vessel damage and invasion, abnormalities in platelet function, and number). New anticoagulants in development for prophylaxis and treatment of VTE include parenteral compounds for once-daily administration (ie, semuloparin) or once-weekly dosing (ie, idraparinux and idrabiotaparinux), as well as orally active compounds (ie, dabigatran, rivaroxaban, apixaban, edoxaban, betrixaban). In the present review, we discuss the pharmacology of the new anticoagulants, the results of clinical trials testing these new compounds in VTE, with special emphasis on studies that included cancer patients, and their potential advantages and drawbacks compared with existing therapies.

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Comparison of antithrombotic and haemorrhagic effects of edoxaban, an oral direct factor Xa inhibitor, with warfarin and enoxaparin in rats

Cited by 23 publications

References 13 publications

Retrospective comparison of three thromboprophylaxis agents, edoxaban, fondaparinux, and enoxaparin, for preventing venous thromboembolism in total knee arthroplasty

Retrospective comparison of three thromboprophylaxis agents, edoxaban, fondaparinux, and enoxaparin, for preventing venous thromboembolism in total knee arthroplasty

Prevention of Stent Thrombosis in Rats by a Direct Oral Factor Xa Inhibitor Edoxaban

Potential role of new anticoagulants for prevention and treatment of venous thromboembolism in cancer patients

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