scholarly journals Update on Edoxaban for the Prevention and Treatment of Thromboembolism: Clinical Applications Based on Current Evidence

2015 ◽  
Vol 2015 ◽  
pp. 1-19 ◽  
Author(s):  
Ali Zalpour ◽  
Thein Hlaing Oo
Keyword(s):  
Vitamin K Antagonists ◽  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Factors ◽  
Current Evidence ◽  
Thrombin Inhibitor ◽  
Prevention And Treatment ◽  
Financial Impacts

Vitamin K antagonists (VKA) and heparins have been utilized for the prevention and treatment of thromboembolism (arterial and venous) for decades. Targeting and inhibiting specific coagulation factors have led to new discoveries in the pharmacotherapy of thromboembolism management. These targeted anticoagulants are known as direct oral anticoagulants (DOACs). Two pharmacologically distinct classes of targeted agents are dabigatran etexilate (Direct Thrombin Inhibitor (DTI)) and rivaroxaban, apixaban, and edoxaban (direct oral factor Xa inhibitors (OFXaIs)). Emerging evidence from the clinical trials has shown that DOACs are noninferior to VKA or low-molecular-weight heparins in the prevention and treatment of thromboembolism. This review examines the role of edoxaban, a recently approved OFXaI, in the prevention and treatment of thromboembolism based on the available published literature. The management of edoxaban in the perioperative setting, reversibility in bleeding cases, its role in cancer patients, the relevance of drug-drug interactions, patient satisfaction, financial impacts, and patient education will be discussed.

scholarly journals The Severity of Intracranial Hemorrhages Measured by Free Hemoglobin in the Brain Depends on the Anticoagulant Class: Experimental Data

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Kyle M. Ware ◽  
Douglas L. Feinstein ◽  
Israel Rubinstein ◽  
Prudhvi Battula ◽  
Jose Otero ◽  
...  
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Hemoglobin Concentration ◽  
Thrombin Inhibitor ◽  
Free Hemoglobin ◽  
Intracranial Hemorrhages ◽  
The Brain

Background and Purpose. Anticoagulant therapy is broadly used to prevent thromboembolic events. Intracranial hemorrhages are serious complications of anticoagulation, especially with warfarin. Direct oral anticoagulants reduce but do not eliminate the risk of intracranial hemorrhages. The aim of this study is to determine the degree of intracranial hemorrhage after application of anticoagulants without additional triggers. Methods. Rats were treated with different anticoagulant classes (vitamin K antagonists, heparin, direct thrombin inhibitor, and factor Xa inhibitor). Brain hemorrhages were assessed by the free hemoglobin concentration in the brain parenchyma. Results. Vitamin K antagonists (warfarin and brodifacoum) significantly increased free hemoglobin in the brain. Among direct oral anticoagulants, thrombin inhibitor dabigatran also significantly increased free hemoglobin in the brain, whereas treatment with factor Xa inhibitor rivaroxaban did not have significant effect on the free hemoglobin concentration. Conclusions. Our data indicates that the severity of brain hemorrhages depends on the anticoagulant class and it is more pronounced with vitamin K antagonists.

Novel oral anticoagulants - key messages for the angiologist

VASA ◽  
2012 ◽  
Vol 41 (3) ◽  
pp. 177-191 ◽  
Author(s):  
Haas ◽  
Spannagl ◽  
M. Schellong
Keyword(s):  
Clinical Evidence ◽  
Vitamin K Antagonists ◽  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Novel Oral Anticoagulants ◽  
Bleeding Complications ◽  
Thrombin Inhibitor ◽  
Clinical Scenarios ◽  
Major Orthopaedic Surgery

Novel oral anticoagulants (NOACs) have become available for different clinical indications such as the prevention of venous thromboembolism (VTE) after major orthopaedic surgery, for the treatment of VTE and stroke prevention in patients with atrial fibrillation (AF). One thrombin inhibitor (dabigatran etexilate) and two factor Xa-inhibitors (rivaroxaban and apixaban) are the most advanced NOACs and therefore, up-to-date information on their evidence and use in clinical practice appears timely. In this review we give a concise overview of the pharmacology and clinical evidence derived from phase 3 clinical trials. Then the meaningfulness of laboratory testing is discussed and recommendations are given for clinical scenarios that may necessitate adjustment of their use. We conclude that NOACs are valuable alternatives to heparins or vitamin K antagonists (VKA) in the prevention and treatment of VTE and for the prevention of stroke in patients with AF. Prescribers should however be aware of special situations and patient populations where the manufacturers’ instructions need to be carefully followed. In particular, patients with comorbidities and co-medications may require individual decision making in order to prevent bleeding complications.

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.

scholarly journals Using direct oral anticoagulants (DOACs) in cancer and other high-risk populations

Hematology ◽  
2015 ◽  
Vol 2015 (1) ◽  
pp. 125-131 ◽  
Author(s):  
Nick van Es ◽  
Harry R. Büller
Keyword(s):  
High Risk ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Thrombin Inhibitor ◽  
Efficacy And Safety ◽  
Practical Advantage ◽  
High Risk Populations

Abstract The major practical advantage of the direct oral anticoagulants (DOACs), comprising the thrombin inhibitor dabigatran and the factor Xa inhibitors apixaban, edoxaban, and rivaroxaban, over vitamin K antagonists is their fixed dosing without the need for laboratory monitoring. With the recent, rapid introduction of the DOACs for the treatment of acute venous thromboembolism (VTE), clinicians are now faced with various questions regarding the efficacy and safety of these compounds overall and in specific high-risk populations. The collective evidence from 6 large clinical trials involving 27,000 patients has demonstrated that DOACs are as effective as vitamin K antagonists (VKA) in preventing recurrent VTE while being associated with a significantly lower risk of major bleeding. These findings are consistent in subgroups of patients with pulmonary embolism, the elderly, and those patients with a high body weight or moderate renal insufficiency, making these agents suitable for a broad spectrum of patients with VTE. DOACs are also an attractive treatment option in patients with VTE and concomitant cancer, thrombotic antiphospholipid syndrome, or heparin-induced thrombocytopenia, but the currently available clinical data is insufficient to make evidence-based recommendations on the use of DOACs in these settings. Several studies evaluating the efficacy and safety of DOACs in these high-risk populations are underway.

The optimal duration of anticoagulant therapy after unprovoked venous thromboembolism – still a challenging issue

VASA ◽  
2017 ◽  
Vol 46 (2) ◽  
pp. 87-95 ◽  
Author(s):  
Giovanna Elmi ◽  
Giuseppe Di Pasquale ◽  
Raffaele Pesavento
Keyword(s):  
Venous Thromboembolism ◽  
Safety Profile ◽  
Vitamin K Antagonists ◽  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Bleeding Risk ◽  
Risk Of Recurrence ◽  
Extended Treatment

Abstract. As about 50 % of patients with unprovoked venous thromboembolism (VTE) will develop new episodes after discontinuing therapy, indefinite treatment is suggested in patients with low or moderate bleeding risk. Baseline and post-baseline factors can help clinicians to identify patients at high risk of recurrence, who require extended treatment. Residual vein obstruction and D-dimer assay have been shown to be suitable methods for assessing the risk of VTE recurrences after a first unprovoked VTE. In treatment for VTE the use of direct oral anticoagulants (DOAC) is growing instead of the standard adjusted dose of vitamin K antagonists. The DOAC safety profile has recently been strengthened with systematic reviews and meta-analyses. Idarucizumab is only approved for the reversal of dabigatran etexilate; intravenous antidotes for factor Xa inhibitors are under development. Their advent is of great interest. In the extended treatment of VTE sulodexide has been demonstrated to significantly decrease the risk of recurrences with an excellent safety profile. Aspirin is substantially less effective than oral anticoagulants in preventing recurrences but could play a role among patients who decided to stop anticoagulants. In conclusion, for the secondary prevention of VTE several options are available, without a recognised best choice regarding the treatment duration and the choice of drugs. An individual strategy taking into account risk of recurrence, bleeding risk, therapeutic options, and patient preferences is appropriate.

scholarly journals Advantages and disadvantages of direct oral anticoagulants in older patients

2018 ◽  
Vol 4 (1) ◽  
Author(s):  
Antonio Cherubini ◽  
Barbara Carrieri ◽  
Paolo Marinelli
Keyword(s):  
Older Patients ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Thrombin Inhibitor ◽  
Vein Thrombosis ◽  
Advantages And Disadvantages ◽  
Gray Areas ◽  
Deep Vein

Atrial fibrillation (AF) and venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism, are conditions that increase with age. Anticoagulant therapy is strongly recommended both in patients with AF for the prevention of cardioembolic stroke, and for treatment of VTE and prevention of recurrent VTE. Until recently, vitamin K antagonists (VKAs) were the only oral drugs for long-term anticoagulation. In the past decade, four direct oral anticoagulants (DOACs) were approved: a direct thrombin inhibitor (dabigatran) and three factor Xa inhibitors (apixaban, rivaroxaban, edoxaban). Despite increasing evidence demonstrating the efficacy and safety of DOACs in older patients, there are still gray areas where the use of VKAs might be valuable.

scholarly journals Factor XI as a Target for New Anticoagulants

2021 ◽  
Vol 41 (02) ◽  
pp. 104-110
Author(s):  
James C. Fredenburgh ◽  
Jeffrey I. Weitz
Keyword(s):  
Vitamin K ◽  
Animal Studies ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Factors ◽  
Clotting Factors ◽  
Factor Xi ◽  
Factor Xi Deficiency

AbstractDespite advances in anticoagulant therapy, thrombosis remains the leading cause of morbidity and mortality worldwide. Heparin and vitamin K antagonists (VKAs), the first anticoagulants to be used successfully for the prevention and treatment of thrombosis, are associated with a risk of bleeding. These agents target multiple coagulation factors. Thus, by activating antithrombin, heparin mainly inhibits factor Xa and thrombin, whereas VKAs lower the levels of the vitamin K–dependent clotting factors. Direct oral anticoagulants, which have replaced VKAs for many indications, inhibit only factor Xa or thrombin. Although the direct oral anticoagulants are associated with less bleeding than VKAs, bleeding remains their major side effect. Epidemiological and animal studies have identified factor XI as a target for potentially safer anticoagulant drugs because factor XI deficiency or inhibition protects against thrombosis and is associated with little or no bleeding. Several factor XI–directed strategies are currently under investigation. This article (1) reviews the rationale for the development of factor XI inhibitors, (2) identifies the agents in most advanced stages of development, (3) describes the results of completed clinical trials and provides a summary of those underway, and (4) highlights the opportunities and challenges for this next generation of anticoagulants.

scholarly journals Reversal Strategies for Intracranial Hemorrhage Related to Direct Oral Anticoagulant Medications

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Alok Dabi ◽  
Aristides P. Koutrouvelis
Keyword(s):  
Side Effects ◽  
Intracranial Hemorrhage ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Cascade ◽  
Reversal Agents ◽  
United States Food ◽  
Life Threatening

Direct oral anticoagulants (DOACs) are a new class of anticoagulants that directly inhibit either thrombin or factor Xa in the coagulation cascade. They are being increasingly used instead of warfarin or other vitamin K antagonists (VKAs). Adverse side effects of DOACs may result in hemorrhagic complications, including life-threatening intracranial hemorrhage (ICH), though to a much lesser degree than VKAs. Currently there are relatively limited indications for DOACS but their usage is certain to expand with the availability of their respective specific reversal agents. Currently, only idarucizumab (antidote for dabigatran) has been United States Food and Drug Administration- (FDA-) approved, but others (andexanet-α and ciraparantag) may be approved in near future, and the development and availability of such reversal agents have the potential to dramatically change the current anticoagulant use by providing reversal of multiple oral anticoagulants. Until all the DOACs have FDA-approved reversal agents, the treatment of the dreaded side effects of bleeding is challenging. This article is an attempt to provide an overview of the management of hemorrhage, especially ICH, related to DOAC use.

scholarly journals Direct oral anticoagulant monitoring: what laboratory tests are available to guide us?

Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 194-197 ◽  
Author(s):  
Ravi Sarode
Keyword(s):  
Clinical Decision Making ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Rapid Assessment ◽  
Clinical Decision ◽  
The United States ◽  
Thrombin Inhibitor ◽  
Thrombin Time ◽  
Clinical Scenarios

Abstract Direct oral anticoagulants (DOACs) are increasingly used in the treatment and prophylaxis of thromboembolism because of several advantages over vitamin K antagonists, including no need for laboratory monitoring. However, it has become increasingly important in certain clinical scenarios to know either actual DOAC concentration (quantitative) or presence of DOAC (qualitative). These clinical conditions include patients presenting with major bleeding or requiring urgent surgery who may need a reversal or hemostatic agent, extremes of body weight, failed therapy, etc. Prothrombin time and activated partial thromboplastin time are variably affected by factor Xa inhibitors (FXaIs) and direct thrombin inhibitor (DTI), respectively, depending on reagents’ sensitivity, and hence, they cannot be relied on confidently. Thrombin time is highly sensitive to very low amounts of DTI; thus, normal value rules out a clinically significant amount. Liquid chromatography mass spectrometry accurately measures DOAC levels but is clinically impractical. Dilute thrombin time and ecarin-based assays using appropriate calibrators/controls provide an accurate DTI level. Anti-Xa assay using corresponding FXaI calibrators/controls provides accurate drug levels. However, these assays are not readily available in the United States compared with some other parts of the world. Heparin assays using anti-Xa activity often have a linear relationship with calibrated FXaI assays, especially at the lower end of on-therapy levels, and they may provide rapid assessment of drug activity for clinical decision making. Currently, there is very limited knowledge of DOAC effect on viscoelastic measurements. Although there is uniformity in expression of DOAC concentrations in nanograms per milliliter, a universal FXaI DOAC assay is urgently needed.

scholarly journals Complex clinical scenarios with the use of direct oral anticoagulants in patients with atrial fibrillation: a multidisciplinary expert advisory board

2020 ◽  
Vol 28 (10) ◽  
pp. 504-513 ◽  
Author(s):  
B. A. Mulder ◽  
J. ten Berg ◽  
H. ten Cate ◽  
N. van Es ◽  
M. E. W. Hemels ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Treatment Guidelines ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Daily Practice ◽  
Advisory Board ◽  
Vascular Surgeon ◽  
Clinical Scenarios

Abstract The risk of developing atrial fibrillation (AF) and the risk of stroke both increase with advancing age. As such, many individuals have, or will develop, an indication for oral anticoagulation to reduce the risk of stroke. Currently, a large number of anticoagulants are available, including vitamin K antagonists, direct thrombin or factor Xa inhibitors (the last two also referred to as direct oral anticoagulants or DOACs), and different dosages are available. Of the DOACs, rivaroxaban can be obtained in the most different doses: 2.5 mg, 5 mg, 15 mg and 20 mg. Many patients develop co-morbidities and/or undergo procedures that may require the temporary combination of anticoagulation with antiplatelet therapy. In daily practice, clinicians encounter complex scenarios that are not always described in the treatment guidelines, and clear recommendations are lacking. Here, we report the outcomes of a multidisciplinary advisory board meeting, held in Utrecht (The Netherlands) on 3 June 2019, on decision making in complex clinical situations regarding the use of DOACs. The advisory board consisted of Dutch cardiovascular specialists: (interventional) cardiologist, internist, neurologist, vascular surgeon and general practitioners invited according to personal title and specific field of expertise.

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