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.

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.

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.

Spotlight on real-world evidence for the treatment of DVT: XALIA

2016 ◽  
Vol 116 (S 02) ◽  
pp. S41-S49 ◽  
Author(s):  
Alexander Turpie ◽  
Walter Ageno
Keyword(s):  
Venous Thromboembolism ◽  
Real World ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Standard Of Care ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Vein Thrombosis ◽  
Real World Evidence ◽  
Recurrent Vte

SummaryVenous thromboembolism (VTE), comprising both deep-vein thrombosis (DVT) and pulmonary embolism (PE), is a serious and common cardiovascular disease associated with the risk of chronic complications, recurrent VTE events and even death. The treatment landscape has, in recent years, seen a paradigm shift from the use of traditional anticoagulants (low-molecular-weight heparin [LMWH] overlapping with and followed by a vitamin K antagonist [VKA]) to non-VKA oral anticoagulants (NOACs). This class of agents, encompassing direct factor Xa inhibitors and direct thrombin inhibitors have shown non-inferior efficacy and better safety to standard of care in randomised controlled trials (RCTs). The direct, oral factor Xa inhibitor rivaroxaban was the first to be approved for treatment of acute DVT and PE and secondary prevention of recurrent VTE events based on data from EINSTEIN DVT and EINSTEIN PE, respectively. Real-world evidence now helps to further support data from RCTs, and also bridges the gap for physicians regarding any areas of clinical uncertainty that may not be addressed by RCTs. XA inhibition with rivaroxaban for Long-term and Initial Anticoagulation in venous thromboembolism (XALIA) was the first large, prospective, observational, real-world study that has investigated the safety and effectiveness profile of rivaroxaban in patients with DVT and PE associated with DVT in routine clinical practice. This article will present the key clinical outcomes from this important global non-interventional study, and will discuss remaining questions to be addressed in Phase IV studies.

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.

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 in the prevention and treatment of venous thromboembolism

2011 ◽  
Vol 152 (25) ◽  
pp. 983-992 ◽  
Author(s):  
Mátyás Keltai ◽  
Katalin Keltai
Keyword(s):  
Venous Thromboembolism ◽  
Treatment Options ◽  
Factor Xa ◽  
Bleeding Risk ◽  
Current Treatment ◽  
Thrombin Inhibitors ◽  
Major Surgery ◽  
Direct Thrombin Inhibitors ◽  
New Anticoagulants ◽  
Prevention And Treatment

Clinical data on the risk factors, incidence, consequences and current treatment options of venous thromboembolism are reviewed. Current guidelines advise anticoagulant treatment for a few weeks or months in immobilized patients treated in hospital, and after major surgery. The initial treatment is based on heparin, followed by vitamin K antagonist treatment. Recently a number of new, partially orally administered medications have undergone clinical investigations and based on the results three of them were also registered for the prevention and treatment of venous thromboembolism. Direct thrombin inhibitors, direct and indirect Factor Xa inhibitors exhibited proven non-inferiority or superiority compared with traditional treatment options. The superior efficacy or non-inferiority was not accompanied with an increase in the bleeding risk. Results of the most important clinical trials are reviewed. Based on these results, prevention and treatment of venous thromboembolism will change substantially in the next future. Orv. Hetil., 2011, 152, 983–992.

Direct thrombin inhibitor melagatran followed by oral ximelagatran in comparison with enoxaparin for prevention of venous thromboembolism after total hip or knee replacement

2003 ◽  
Vol 89 (02) ◽  
pp. 288-296 ◽  
Author(s):  
Giancarlo Agnelli ◽  
Alexander Cohen ◽  
Ola Dahl ◽  
Patrick Mouret ◽  
Nadia Rosencher ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Knee Replacement ◽  
Thrombin Inhibitors ◽  
Thrombin Inhibitor ◽  
Direct Thrombin Inhibitors ◽  
Double Blind Study ◽  
Double Blind ◽  
Total Hip ◽  
Vein Thrombosis ◽  
Major Orthopaedic Surgery

SummaryWe evaluated whether a postoperative regimen with melagatran followed by oral ximelagatran, two new direct thrombin inhibitors, was an optimal regimen for thromboprophylaxis in major orthopaedic surgery. In a double-blind study, 2788 patients undergoing total hip or knee replacement were randomly assigned to receive for 8 to 11 days either 3 mg of subcutaneous melagatran started 4-12 h postoperatively, followed by 24 mg of oral ximelagatran twice-daily or 40 mg of subcutaneous enoxaparin once-daily, started 12 h preoperatively. Ximelagatran was to be initiated within the first two postoperative days. The primary efficacy endpoint was venous thromboembolism (deep-vein thrombosis detected by mandatory venography, pulmonary embolism or unexplained death). The main safety endpoint was bleeding. Venous thromboembolism occurred in 355/1146 (31.0%) and 306/1122 (27.3%) patients in the ximelagatran and enoxaparin group, respectively, a difference in risk of 3.7% in favour of enoxaparin (p = 0.053). Bleeding was comparable between the two groups.

Anticoagulation Treatment in Venous Thromboembolism: Options and Optimal Duration

2021 ◽  
Vol 27 ◽  
Author(s):  
Stavrianna Diavati ◽  
Marios Sagris ◽  
Dimitrios Terentes-Printzios ◽  
Charalambos Vlachopoulos
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Anticoagulation Therapy ◽  
Factor Xa ◽  
Coagulation Cascade ◽  
Clinical Genetic ◽  
Vein Thrombosis ◽  
Anticoagulation Treatment ◽  
Molecular Pathophysiology ◽  
Deep Vein

: Venous thromboembolism (VTE), clinically presenting as deep-vein thrombosis (DVT) or pulmonary embolism (PE), constitutes a major global healthcare concern with severe complications, long-term morbidity and mortality. Although several clinical, genetic and acquired risk factors for VTE have been identified, the molecular pathophysiology and mechanisms of disease progression remain poorly understood. Anticoagulation has been the cornerstone of therapy for decades, but there still are uncertainties regarding primary and secondary VTE prevention, as well as optimal therapy duration. In this review we discuss the role of factor Xa in coagulation cascade and the different choices of anticoagulation therapy based on patients’ predisposing risk factors and risk of event recurrence. Further, we compare newer agents to traditional anticoagulation treatment, based on most recent studies and guidelines.

Sign in / Sign up

Export Citation Format

Share Document