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Jessica W Skelley, C Whitney White, Angela R Thomason
To review the use of the direct oral anticoagulant (DOAC) agents in inherited thrombophilia based on the literature. MEDLINE, International Pharmaceutical Abstracts, and Google Scholar searches (1970-May 2016) were conducted for case reports, case series, retrospective cohorts, or clinical trials using the key words: protein C deficiency, protein S deficiency, antithrombin deficiency, activated protein C resistance, Factor V Leiden, hypercoagulable, NOACs, dabigatran, apixaban, rivaroxaban, betrixaban, edoxaban, Xa inhibitor, direct thrombin inhibitor...
October 12, 2016: Journal of Thrombosis and Thrombolysis
Junhao Xing, Lingyun Yang, Yifei Yang, Leilei Zhao, Qiangqiang Wei, Jian Zhang, Jinpei Zhou, Huibin Zhang
Coagulation factor Xa (fXa) is a particularly attractive target for the development of effective and safe anticoagulants. In this study, novel 2,3-dihydroquinazolin-4(1H)-one derivatives were designed as potential fXa inhibitors based on anthranilamide structure which has been reported in our previous research. The experimental data showed that most of the designed compounds exhibited significant in vitro potency against fXa. Among them, compound 8e displayed the strongest potency against fXa with the IC50 value of 21 nM and highly selectivity versus thrombin (IC50 = 67 μM) and excellent in vitro antithrombotic activity with its 2 × PT value of 1...
September 19, 2016: European Journal of Medicinal Chemistry
Antonio Bellasi, Luca Di Lullo, Gianvincenzo Melfa, Claudio Minoretti, Carlo Ratti, Carlo Campana, Maurizio Volpi, Stefano Mangano, Biagio Di Iorio, Mario Cozzolino
The new or direct oral anticoagulants [new oral anticoagulants (NOAC) or direct oral anticoagulants (DOAC)] were launched in the Italian market in 2013. Although these compounds share common pharmacological indications with vitamin K antagonists (warfarin or acenocumarol), they have different mechanisms of action, do not require a constant anticoagulant monitoring but are more efficacious and safer than vitamin K antagonists. The use of these molecules (Dabigatran, Apixaban, Rivaroxaban, Betrixaban, Edoxaban) is constantly rising in daily practice...
July 2016: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
Yi-Ping Dang, Yun-Fei Chen, Yi-Qing Li, Lei Zhao
Deep Vein Thrombosis (DVT) has been known as a common medical problem all over the world. Thrombus traveling in blood vessels may lead to pulmonary embolism (PE), associated with high rates of mortality. Anticoagulant therapy is the mainstay treatment of DVT. Common anticoagulants, Vitamin K antagonists (VKAs) unfractionated heparin (UFH) and Low-molecular-weight heparin (LMWH) have been used in clinical application over decades, but can increase the risk of hemorrhage. Thereby, several new oral anticoagulants (NOACs) have been developed, which includes direct thrombin inhibitors (DTI) and direct factor Xa inhibitors...
June 8, 2016: Mini Reviews in Medicinal Chemistry
Alexander T Cohen, Robert A Harrington, Samuel Z Goldhaber, Russell D Hull, Brian L Wiens, Alex Gold, Adrian F Hernandez, C Michael Gibson
BACKGROUND: Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. METHODS: Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days...
August 11, 2016: New England Journal of Medicine
Noel C Chan, Vinai Bhagirath, John W Eikelboom
Venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism, is a common and potentially preventable cause of morbidity and mortality. Unfractionated heparin, low-molecular-weight heparin, and warfarin have been the cornerstone of VTE prevention and treatment but are being replaced by recently approved non-vitamin K antagonist oral anticoagulants (NOACs): dabigatran, rivaroxaban, apixaban, and edoxaban. The NOACs are at least as effective and as safe as heparins and warfarin for VTE prevention and treatment and are more convenient because they have a low propensity for food and drug interactions and are given in fixed doses without routine coagulation monitoring...
2015: Vascular Health and Risk Management
G D Barnes, W Ageno, J Ansell, S Kaatz
No abstract text is available yet for this article.
June 2015: Journal of Thrombosis and Haemostasis: JTH
Andreas Greinacher, Thomas Thiele, Kathleen Selleng
Several new anticoagulants have entered the clinical arena or are under clinical development. These drugs include indirect (fondaparinux) and direct oral factor Xa inhibitors (rivaroxaban, apixaban, edoxaban, betrixaban), and the direct thrombin inhibitor dabigatran. Especially the oral direct FXa and FIIa inhibitors overcome many of the shortcomings of heparins and vitamin K antagonists (VKAs). They are administered orally at a fixed dose; regular monitoring is not necessary; interaction with other drugs or nutrition occur less than with VKAs and they are at least as effective as VKAs for most indications tested...
May 2015: Thrombosis and Haemostasis
Emmanuel J Favaloro, Giuseppe Lippi
A new generation of antithrombotic agents has recently emerged. These provide direct inhibition of either thrombin (factor IIa [FIIa]) or FXa, and are increasingly replacing the classical anticoagulants (heparin and coumarins such as warfarin) in clinical practice for a variety of conditions. These agents have been designated several acronyms, including NOACs, DOACs, and TSOACs, respectively, referring to new (novel; non-vitamin K antagonist) oral anticoagulants, direct oral anticoagulants, and target-specific oral anticoagulants, and currently include dabigatran (FIIa inhibitor), and rivaroxaban, apixaban, edoxaban, and betrixaban (FXa inhibitors)...
March 2015: Seminars in Thrombosis and Hemostasis
Brandon J McMahon, Hau C Kwaan
One of the major advances in the management of thrombosis is arguably the introduction of the new non-vitamin K antagonist oral anticoagulants (NOACs). These are small molecules, designed to directly inhibit specific steps in the coagulation pathway, with dabigatran (Pradaxa), inhibiting thrombin and rivaroxaban (Xarelto), apixiban (Eliquis), edoxaban (Lixiana), and betrixaban being factor Xa inhibitors. They have several advantages over vitamin K antagonists such as warfarin, with more predictable bioavailability, fewer drug interactions, and improved safety, especially intracranial hemorrhage...
March 2015: Seminars in Thrombosis and Hemostasis
Alexander T Cohen, Robert Harrington, Samuel Z Goldhaber, Russell Hull, C M Gibson, Adrian F Hernandez, Alex Gold
No abstract text is available yet for this article.
January 2015: American Heart Journal
S Meddahi, M-M Samama
Heparins and vitamin K antagonists (VKA) used commonly are the standard treatment of venous and arterial thromboses. They are very efficient and safe, but have some limitations: iatrogenicity, laboratory monitoring, parenteral use for heparins and fondaparinux. Nowadays, four new inhibitors of factor Xa are used orally (rivaroxaban, apixaban, edoxaban, betrixaban), and they are at least as efficient as heparins and vitamin K antagonists. The objective is to substitute these indirect inhibitors of factor Xa (heparins, low molecular weight heparins and fondaparinux) in the prevention of venous and arterial thromboembolic episodes...
May 2014: Journal des Maladies Vasculaires
Alexander T Cohen, Robert Harrington, Samuel Z Goldhaber, Russell Hull, C Michael Gibson, Adrian F Hernandez, Michael M Kitt, Todd J Lorenz
Randomized clinical trials have identified a population of acute medically ill patients who remain at risk for venous thromboembolism (VTE) beyond the standard duration of therapy and hospital discharge. The aim of the APEX study is to determine whether extended administration of oral betrixaban (35-42 days) is superior to a standard short course of prophylaxis with subcutaneous enoxaparin (10 ± 4 days followed by placebo) in patients with known risk factors for post-discharge VTE. Patients initially are randomized to receive either betrixaban or enoxaparin (and matching placebo) in a double dummy design...
March 2014: American Heart Journal
Noel C Chan, Jack Hirsh, Jeffrey S Ginsberg, John W Eikelboom
The recently introduced oral anticoagulants, dabigatran, rivaroxaban and apixaban, were shown, in randomized controlled trials, to be at least as effective and safe as monitored warfarin therapy for the treatment of venous thromboembolism and stroke prevention in atrial fibrillation. These new oral anticoagulants have predictable pharmacology, less variability in anticoagulant effect and fewer drug and food interactions than warfarin, allowing unmonitored and fixed dosing, which renders their use appealing...
January 2014: Future Cardiology
Michael Palladino, Geno Merli, Lynda Thomson
INTRODUCTION: For over 60 years vitamin K antagonists have been the mainstay of oral therapy for treatment and prevention of venous and arterial thromboembolic disease. The emergence of two new classes of orally administered anticoagulants, direct thrombin and factor Xa inhibitors have drastically changed the landscape in the management of these disease states. Betrixaban , an orally administered direct factor Xa inhibitor, is entering a Phase III trial and undergoing investigation for similar indications as apixaban, dabigatran and rivaroxaban...
November 2013: Expert Opinion on Investigational Drugs
Karsten M H Bruins Slot, Eivind Berge
BACKGROUND: Anticoagulant treatment with vitamin K antagonists (VKAs) is aimed at preventing thromboembolic complications and has been the therapy of choice for most people with non-valvular atrial fibrillation (AF) for many decades. A new class of anticoagulants, the factor Xa inhibitors, appear to have several pharmacological and practical advantages over VKAs. OBJECTIVES: To assess the effectiveness and safety of treatment with factor Xa inhibitors versus VKAs for the prevention of cerebral or systemic embolic events in people with AF...
2013: Cochrane Database of Systematic Reviews
Gentian Denas, Vittorio Pengo
INTRODUCTION: The introduction of novel anticoagulants has had contrasting effects on the agents in the pipeline, fueling the development of some and sinking the others. The complexity of the coagulation cascade offers interesting inhibition choices that might become valid treatment options. AREAS COVERED: This review will highlight some of the anticoagulants in the pipeline. Following the success of the direct thrombin and FXa inhibitors already in the market, new agents are being tested...
October 2013: Expert Opinion on Investigational Drugs
Maryna Bondarenko, Christophe Curti, Marc Montana, Pascal Rathelot, Patrice Vanelle
Venous thromboembolism (VTE) is a serious disease that is often neglected, and effective and safe antithrombotic treatments are a public health priority. New antithrombotics such as rivaroxaban, apixaban, betrixaban, edoxaban, darexaban, TAK-442, LY517717, eribaxaban, otamixaban are being developed to overcome current therapeutic limitations. The new oral anticoagulants and parenteral otamixaban are under evaluation in clinical trials for VTE treatment, for VTE prevention in orthopedic surgery, for stroke prevention in patients with atrial fibrillation and for cardiovascular event prevention in patients with acute coronary syndrome...
2013: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
Antonio Gómez-Outes, M Luisa Suárez-Gea, Ramón Lecumberri, Ana Isabel Terleira-Fernández, Emilio Vargas-Castrillón, Eduardo Rocha
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...
2013: Vascular Health and Risk Management
K Huber, S J Connolly, A Kher, F Christory, G-A Dan, R Hatala, R G Kiss, B Meier, B Merkely, B Pieske, T Potpara, J Stępińska, N Vene Klun, D Vinereanu, P Widimský
Atrial fibrillation (AF) is associated with an increased risk of thromboembolism, and is the most prevalent factor for cardioembolic stroke. Vitamin K antagonists (VKAs) have been the standard of care for stroke prevention in patients with AF since the early 1990s. They are very effective for the prevention of cardioembolic stroke, but are limited by factors such as drug-drug interactions, food interactions, slow onset and offset of action, haemorrhage and need for routine anticoagulation monitoring to maintain a therapeutic international normalised ratio (INR)...
June 2013: International Journal of Clinical Practice
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