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Cerebrovascular disease in the elderly patient
Published in Wilbert S. Aronow, Jerome L. Fleg, Michael W. Rich, Tresch and Aronow’s Cardiovascular Disease in the Elderly, 2019
A new category of anticoagulants for primary prevention of stroke in AF have been developed that may have some advantages over anticoagulation with warfarin: the direct thrombin inhibitor dabigatran and the factor Xa inhibitors rivaroxaban, apixaban, and edoxaban (100-103). Dabigatran 150 mg twice daily was associated with a lower incidence of stroke compared to warfarin and equal incidence of hemorrhagic complications (100). However, in post-marketing experience, the higher dose of dabigatran has been associated higher risk of hemorrhagic complications than the original study, particularly in the elderly. Rivaroxaban 20 mg daily was more effective than warfarin with an equal rate of hemorrhagic complications but a significantly lower rate of intracranial hemorrhage (101). Apixaban 5 mg twice daily had a lower risk of stroke compared to warfarin as well as lower rate of hemorrhagic complications. Apixaban must be dose adjusted in patients above 80 with low body weight, elevated creatinine, and certain drug interactions (85,102). The slightly higher efficacy and lower rate of hemorrhagic complications has made apixaban a popular choice among cardiologists and vascular neurologists. Edoxaban, the last to be approved, was approved at a dose of 60 mg daily for secondary prevention of stroke in AF. When compared to warfarin, the hazard of ischemic stroke was equivalent but hemorrhagic stroke significantly lower (103).
Briefing Therapeutic Approaches in Anticoagulant, Thrombolytic, and Antiplatelet Therapy
Published in Debarshi Kar Mahapatra, Sanjay Kumar Bharti, Medicinal Chemistry with Pharmaceutical Product Development, 2019
Edoxaban was approved in July 2011 in Japan for the prevention of venous thromboembolisms (VTE) following lower-limb orthopedic surgery. It was also approved by the FDA in January 2015 for the prevention of stroke and non-central nervous system systemic embolism. It inhibits free factor Xa and prothrombinase activity and inhibits thrombin-induced platelet aggregation [50]. Portola submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking approval to market betrixaban for extended-duration prophylaxis of venous thromboembolism (VTE) in acute medically ill patients with risk factors for VTE [51]. Darexaban (YM150) is a direct inhibitor of factor Xa created by Astellas Pharma. The development of darexaban was discontinued in September 2011 [52]. Otamixaban is an experimental injectable anticoagulant direct factor Xa inhibitor that was investigated for the treatment for acute coronary syndrome. In 2013, Sanofi announced that the drug candidate showed poor performance in a Phase III clinical trial [53]. The advantages of the xabans over vitamin K antagonists include no requirement for routine anticoagulation monitoring as well as a fast and reliable onset of action [54–56].
Medical treatment of acute deep venous thrombosis and pulmonary embolism
Published in Peter Gloviczki, Michael C. Dalsing, Bo Eklöf, Fedor Lurie, Thomas W. Wakefield, Monika L. Gloviczki, Handbook of Venous and Lymphatic Disorders, 2017
Andrea T. Obi, Thomas W. Wakefield
Edoxaban (Savaysa®, Daiichi Sankyo) is the most recently approved agent for treatment of DVT.22 It is currently FDA approved for the prevention of stroke and non-central nervous system systemic embolism in patients with non-valvular atrial fibrillation, as well as for the treatment of DVT and PE in patients who have been treated with a parenteral anticoagulant for 5–10 days. Edoxaban carries a boxed warning stating that the novel anticoagulant is less effective in atrial fibrillation patients with a creatinine clearance of >95 mL/minute, and that kidney function should be assessed prior to starting treatment. According to the FDA, patients with a creatinine clearance of >95 mL/minute have a greater risk of stroke compared with similar patients treated with warfarin. Edoxaban is the only agent specifically tested at a lower dose in patients at high risk of bleeding complications (low body weight and/or decreased creatinine clearance).22
Biopharmaceutics considerations for direct oral anticoagulants
Published in Drug Development and Industrial Pharmacy, 2021
Rafael Pereira de Andrade, Tamires Guedes Caldeira, Bárbara Vasconcelos Vasques, André Luís Morais Ruela, Jacqueline de Souza
The oral bioavailability of edoxaban is around 62% [43,89,98] and it exhibits dose proportional pharmacokinetics in the range of 10 to 150 mg [94]. Edoxaban should not be used in patients with CrCl >95 ml/min because of increased risk of ischemic stroke compared to warfarin at the highest dose studied (60 mg). The recommended dose is 60 mg orally, once daily. However, for patients with CrCl 15 to 50 ml/min or body weight ≤ 60 kg or who use certain P-gp inhibitors (e.g. verapamil and quinidine), the recommended dose must be reduced to 30 mg orally, once daily. Edoxaban is not recommended in patients with moderate or severe hepatic impairment. In addition, its use should be discontinued in nursing mothers. On the other hand, age, gender and ethnicity do not affect systemic exposure to edoxaban [94]. Table 2 describes the pharmacokinetics parameters of this drug.
Edoxaban for the treatment of pulmonary embolism in hospitalized COVID-19 patients
Published in Expert Review of Clinical Pharmacology, 2021
Valerio Langella, Roberta Bottino, Antonio Asti, Giulio Maresca, Gisella Di Palma, Domenico Pomponi, Claudia Sassone, Egidio Imbalzano, Vincenzo Russo
From 384 consecutive patients with laboratory confirmed COVID-19 admitted to our institution for acute dyspnea from 20 May 2020 to 20 November 2020, we retrospectively selected those with computer tomography (CT) detected PE at admission. All patients treated with edoxaban during hospitalization were included in the analysis. Baseline characteristics such as medical history, physical examination, laboratory evaluation, pharmacological therapy, chest X-Ray and CT features have been collected. Clinical outcomes as ARDS at admission or developed during hospitalization, resolution of PE at CT, length of hospitalization, overall bleedings and mortality were collected and analyzed. Baseline characteristics and clinical outcomes were compared between patients with ARDS at admission and patients without ARDS at admission as well as between patients with PE resolution and patients without PE resolution. ARDS diagnosis was defined according to the Berlin definition [10]. According to our hospital protocol, a follow-up CT scan evaluation performed at one and three months from the PE diagnosis or at hospital discharge, whichever came first. Complete PE resolution was defined as a CT pulmonary angiogram on follow-up that showed no evidence of PE in any vessel [11].
Extended oral anticoagulation after incident venous thromboembolism – a paradigm shift?
Published in Expert Review of Cardiovascular Therapy, 2020
Ida Ehlers Albertsen, Gregory Piazza, Mette Søgaard, Peter Brønnum Nielsen, Torben Bjerregaard Larsen
The NOACs for VTE treatment include the direct thrombin inhibitor dabigatran, and three direct Factor Xa inhibitors rivaroxaban, apixaban, and edoxaban. For treatment of acute VTE, dabigatran and edoxaban are both preceded by treatment with a parenteral anticoagulant such as unfractionated heparin or low molecular weight heparin (lead-in period of ≥5 days), whereas apixaban and rivaroxaban can be administered from day one as totally oral monotherapy. Anticoagulant therapies available during the phases of VTE treatment are summarized in Figure 1. In four major randomized clinical trials, dabigatran [26], rivaroxaban [27,28], and apixaban [29] have all been investigated for extended treatment (after initial acute treatment in 3–18 months). Summary of the findings from anticoagulant extension trials is listed in Table 1. The drugs have all been proven effective in reducing recurrence risk, but the benefit is partially offset by a risk of bleeding. Edoxaban has not been formally investigated in an extension trial; however, a sub-analysis of the HOKUSAI-VTE showed that after 12 months total treatment, treatment with edoxaban reduced the risk of recurrence compared with warfarin (HR 0.78; 0.35–1.72). Edoxaban was associated with less major bleeding (HR 0.45; 0.22–0.92) but higher clinically relevant bleeding (HR 0.97; 0.77–1.22) [30].