scholarly journals Current Status of New Anticoagulants in the Management of Venous Thromboembolism

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Roberto C. Montoya ◽  
Ajeet Gajra
Keyword(s):  
Venous Thromboembolism ◽  
Vitamin K Antagonists ◽  
Dabigatran Etexilate ◽  
New Drugs ◽  
Thrombin Inhibitors ◽  
Current Status ◽  
Direct Thrombin Inhibitors ◽  
Factor X ◽  
Vast Number ◽  
New Anticoagulants

Venous Thromboembolism, manifested as deep venous thrombosis and pulmonary embolism, is a common problem associated with significant morbidity, mortality, and resource expenditure. Unfractionated heparin, low-molecular-weight heparin, and vitamin K antagonists are the most common treatment and prophylaxis, and have demonstrated their efficacy in a vast number of previous studies. Despite their broad use, these agents have important limitations that have led to the development of new drugs in a bid to overcome the disadvantages of the old ones without decreasing their therapeutic effect. These novel medications, some approved and others in different stages of development, include direct thrombin inhibitors like dabigatran etexilate, and direct activated factor X inhibitors like rivaroxaban. The current paper will review the characteristics, clinical trial results, and current and potential therapeutic uses of these new agents with a focus on the categories of direct thrombin inhibitors and activated factor X inhibitors.

scholarly journals New anticoagulants for the treatment of venous thromboembolism

2016 ◽  
Vol 42 (2) ◽  
pp. 146-154 ◽  
Author(s):  
Caio Julio Cesar dos Santos Fernandes ◽  
José Leonidas Alves Júnior ◽  
Francisca Gavilanes ◽  
Luis Felipe Prada ◽  
Luciana Kato Morinaga ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Vitamin K Antagonists ◽  
Factor Xa ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Vein Thrombosis ◽  
New Anticoagulants ◽  
Acute Pulmonary Thromboembolism ◽  
Deep Vein

Worldwide, venous thromboembolism (VTE) is among the leading causes of death from cardiovascular disease, surpassed only by acute myocardial infarction and stroke. The spectrum of VTE presentations ranges, by degree of severity, from deep vein thrombosis to acute pulmonary thromboembolism. Treatment is based on full anticoagulation of the patients. For many decades, it has been known that anticoagulation directly affects the mortality associated with VTE. Until the beginning of this century, anticoagulant therapy was based on the use of unfractionated or low-molecular-weight heparin and vitamin K antagonists, warfarin in particular. Over the past decades, new classes of anticoagulants have been developed, such as factor Xa inhibitors and direct thrombin inhibitors, which significantly changed the therapeutic arsenal against VTE, due to their efficacy and safety when compared with the conventional treatment. The focus of this review was on evaluating the role of these new anticoagulants in this clinical context.

Old and new anticoagulants

2011 ◽  
Vol 31 (01) ◽  
pp. 21-27 ◽  
Author(s):  
U. Harbrecht
Keyword(s):  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
New Oral Anticoagulants ◽  
Thrombin Inhibitors ◽  
Clotting Factor ◽  
Direct Thrombin Inhibitors ◽  
Self Monitoring ◽  
New Anticoagulants ◽  
Gastrointestinal Side Effects

SummaryVitamin-K-antagonists (VKA) and heparins have been complementary anticoagulants for prevention and treatment of thrombosis for almost 70 years. In contrast to heparins, VKA have not been modified pharmacologically, however treatment surveillance has improved by introducing INR and self-monitoring/management. Disclosure of the molecular basis of interaction with VKORC1, the target enzyme of VKA, has helped to better understand coumarin sensitivity and resistance. New oral anticoagulants have now been approved and stimulated expectations in patients and physicians to get rid of the burdening frequent controls of VKA without loss of efficacy and safety.This review will summarize the development and profile of the new substances. Main difference compared to VKA is their direct mode of action against one clotting factor which is factor IIa in dabigatran and factor Xa in rivaroxaban and other “xabanes” currently under intensive investigation. Half lifes of the new anticoagulants are much shorter than that of the mainly used coumarins (phenprocoumon, warfarin), making “anticoagulation bridging” unnecessary before surgery. Therapeutic width of direct thrombin inhibitors and factor Xa inhibitors is broader and they are given at fixed doses. Clinical studies in thromboprophylaxis, thromboembolism and atrial fibrillation indicate at least non-inferiority or even superior efficacy compared with enoxaparin and VKA at comparable safety outcomes. Limitations of the new substances may arise from gastrointestinal side effects, mode of metabolism and route of elimination. Specific antidots are not available for none of them.Undoubtedly, the new oral anticoagulants are very promising. But, although thousands of study patients already have been treated, there are questions to be answered such as treatment adherence in absence of monitoring, safety and efficacy in risk patients, dosage adjustment and interactions with other drugs, before conclusions can be drawn towards their potential to replace VKA.

New anticoagulants – towards the development of an "ideal" anticoagulant

VASA ◽  
2009 ◽  
Vol 38 (1) ◽  
pp. 13-29 ◽  
Author(s):  
Haas
Keyword(s):  
Unfractionated Heparin ◽  
Vitamin K Antagonists ◽  
Dabigatran Etexilate ◽  
Factor Xa ◽  
Rapid Onset ◽  
Factor Ix ◽  
Thrombin Inhibitors ◽  
Therapeutic Monitoring ◽  
Direct Thrombin Inhibitors ◽  
Onset Of Action

Currently available anticoagulants, such as unfractionated heparin, low molecular weight heparins and vitamin K antagonists, have proved effective in the prevention and treatment of thromboembolic disorders. However, these drugs have some drawbacks, such as unpredictability (in the case of unfractionated heparin), non-specificity and parenteral mode of administration, which limit their use in the clinical setting. There is a need for new agents with efficacy similar to that of these classes of anticoagulants and none of their associated drawbacks. Advances are being made in the development of more convenient and more specific drugs, with the aim to improve substantially the prevention and management of thromboembolic disorders. This review will emphasize how the development of an ideal anticoagulant, with potential benefits including high efficacy, safety, low levels of bleeding, fixed dosing, rapid onset of action, ability to bind clot-bound coagulation factors and no requirement for therapeutic monitoring, is a considerable challenge. This review will present the most relevant preclinical data, as well as the clinical studies performed to date, for several drug classes. Direct thrombin inhibitors, such as dabigatran etexilate, will be reviewed, as well as indirect (fondaparinux and idraparinux) and direct (rivaroxaban, apixaban, among others) Factor Xa inhibitors, Factor IXa inhibitors and monoclonal antibodies against Factor IX/IXa.

Review of the Target-Specific Oral Anticoagulants in Development for the Treatment and Prevention of Venous Thromboembolism

2016 ◽  
Vol 29 (4) ◽  
pp. 392-405 ◽  
Author(s):  
Sandeep Devabhakthuni ◽  
Connie H. Yoon ◽  
Kathleen J. Pincus
Keyword(s):  
Venous Thromboembolism ◽  
Clinical Decision Making ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Bleeding Risk ◽  
Clinical Decision ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Treatment And Prevention

Anticoagulation therapy is often indicated for the treatment and prevention of venous thromboembolism (VTE). Despite advances in anticoagulant management with parenteral anticoagulants and vitamin K antagonists, limitations to their use still exists, leading to investigation of alternative anticoagulants such as factor Xa inhibitors and direct thrombin inhibitors. To date, 3 target-specific oral anticoagulants (TSOACs) are Food and Drug Administration approved; several other agents are currently in development to optimize VTE management and minimize bleeding risks. The objective of this systematic review article is to provide clinicians an overview of the clinical evidence on the investigational TSOACs for the treatment and prevention of VTE. Of the agents in development, edoxaban holds the most promise due to robust data supporting its clinical benefit with a similar bleeding risk to currently approved agents. Clinicians should understand the TSOACs under investigation, since differences in pharmacokinetics and pharmacodynamics may influence clinical decision making and agent selection for management of VTE. Currently, no direct comparisons between TSOACs have been conducted. Agents under investigation have yet to overcome the major limitations of the currently existing TSOACs. Further studies are necessary to clarify which TSOAC agent is best for management of VTE in clinical practice.

scholarly journals Direct oral anticoagulants and venous thromboembolism

2016 ◽  
Vol 25 (141) ◽  
pp. 295-302 ◽  
Author(s):  
Massimo Franchini ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Venous Thromboembolism ◽  
Vitamin K Antagonists ◽  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Thrombin Inhibitors ◽  
Vein Thrombosis ◽  
Direct Anticoagulants ◽  
Deep Vein

Venous thromboembolism (VTE), consisting of deep vein thrombosis and pulmonary embolism, is a major clinical concern associated with significant morbidity and mortality. The cornerstone of management of VTE is anticoagulation, and traditional anticoagulants include parenteral heparins and oral vitamin K antagonists. Recently, new oral anticoagulant drugs have been developed and licensed, including direct factor Xa inhibitors (e.g. rivaroxaban, apixaban and edoxaban) and thrombin inhibitors (e.g. dabigatran etexilate). This narrative review focusses on the characteristics of these direct anticoagulants and the main results of published clinical studies on their use in the prevention and treatment of VTE.

Emerging anticoagulants for the treatment of venous thromboembolism

2006 ◽  
Vol 96 (09) ◽  
pp. 274-284 ◽  
Author(s):  
Jeffrey Weitz
Keyword(s):  
Venous Thromboembolism ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
New Drugs ◽  
New Anticoagulants ◽  
Postphlebitic Syndrome ◽  
Long Acting ◽  
Two Stages

SummaryAnticoagulant therapy is the cornerstone of treatment of venous thromboembolism (VTE). Such treatment is divided into two stages. Rapid initial anticoagulation is given to minimize the risk of thrombus extension and fatal pulmonary embolism, whereas extended anticoagulation is aimed at preventing recurrent VTE, thereby reducing the risk of postphlebitic syndrome. With currently available drugs, immediate anticoagulation can only be achieved with parenteral agents, such as heparin, low-molecular-weight heparin, or fondaparinux. Extended treatment usually involves the administration of vitamin K antagonists,such as warfarin. Emerging anticoagulants have the potential to streamline VTE treatment. These agents include idraparinux, a long-acting synthetic pentasaccharide that is given subcutaneously on a once-weekly basis, and new oral anticoagulants that target thrombin or factor Xa. This paper i) reviews the pharmacology of these agents, ii) outlines their potential strengths and weaknesses, iii) describes the results of clinical trials with these new drugs, and iv) identifies the evolving role of new anticoagulants in the management of VTE.

Direct oral anticoagulants – new challenge for laboratory medicine

2015 ◽  
Vol 51 (3) ◽  
pp. 221-228
Author(s):  
Anna Raszeja-Specht ◽  
Anna Michno
Keyword(s):  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Thrombin Inhibitors ◽  
Thrombin Inhibitor ◽  
Direct Thrombin Inhibitors ◽  
Factor X ◽  
Clotting Time ◽  
Coagulation Tests ◽  
New Generation

A new generation of oral anticoagulants, direct thrombin or activated factor X inhibitors gradually replaces the existing antithrombotic agents, administered parenterally (heparin) or orally (vitamin K antagonists). Currently, the most widely used class of direct oral anticoagulants (DOACs) are the direct thrombin inhibitor dabigatran and rivaroxaban, apixaban and edoxaban – Xa inhibitors. Although previous reports suggested that DOACs therapy does not require laboratory screening, recently the new indications for monitoring and the types of laboratory tests used in the evaluation of the effectiveness of treatment have been updated. To quantify the activity of direct thrombin inhibitors a dilute thrombin clotting time (dTT) or ecarin clotting time (ECT) is recommended. The effect of rivaroxaban and apixaban can be determined by anti-Xa activity assay when calibrated with a rivaroxaban and apixaban standard. Observed changes in routine coagulation tests such as activated partial thromboplastin time (APTT), and prothrombin time (PT), with varying degrees of severity, can only be an indicator of an additional screening, which is the emergency clinical interventions.

Anticoagulant Therapy in Atrial Fibrillation – Time for a Change?

2009 ◽  
Vol 5 (2) ◽  
pp. 57
Author(s):  
Raffaele De Caterina ◽  
Giulia Renda ◽  
◽  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Dabigatran Etexilate ◽  
Anticoagulation Therapy ◽  
New Drugs ◽  
Phase Iii ◽  
Therapeutic Window ◽  
Randomized Evaluation ◽  
New Anticoagulants

Although to date warfarin and other vitamin K antagonists have clearly had the greatest efficacy among commonly available treatments in preventing stroke in atrial fibrillation, their use is associated with a substantial risk of major bleeding and is impractical because of their narrow therapeutic window, their interaction with drugs and foods and the need for frequent coagulation monitoring. Several new anticoagulants are undergoing phase III clinical trials in atrial fibrillation with the aim of demonstrating non-inferiority compared with vitamin K antagonists or superiority compared with aspirin in patients in whom vitamin K antagonists are contraindicated or not tolerated. In the recently released Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial, the first such drug, dabigatran etexilate, was proved substantially equivalent to 2–3 international normalised ratio (INR)-adjusted warfarin at the dosage of 110mg twice a day (BID), with superior efficacy at a dosage of 150mg BID. With these new drugs, cardiologists and internists are witnessing a real revolution in the thromboprophylaxis in atrial fibrillation.

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