scholarly journals The current place of direct oral anticoagulants in the prevention/treatment of venous thromboembolism

2020 ◽  
Vol 70 (5) ◽  
pp. 284-296
Author(s):  
Maja Tomić
Keyword(s):  
Venous Thromboembolism ◽  
High Risk ◽  
Secondary Prevention ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Comparable Efficacy ◽  
Thrombin Inhibitor ◽  
Medical Patients ◽  
Vte Prophylaxis

Venous thromboembolism (VTE; includes deep venous thrombosis, DVT, and pulmonary embolism, PE) represents the third most common acute cardiovascular syndrome. Contemporary VTE management comprises primary prevention in high-risk patients, treatment of established VTE, and prevention of its recurrence (secondary prevention). Anticoagulants are the basis of VTE pharmacological prophylaxis and treatment. For several decades, parenteral (heparin and low-molecular-weight heparins, LMWHs) and oral anticoagulants (vitamin K antagonists, VKAs) have been the cornerstone of VTE prevention/treatment. The introduction of direct oral anticoagulants (DOACs: thrombin inhibitor dabigatran and Xa inhibitors rivaroxaban, apixaban, edoxaban, and betrixaban) markedly improved the management of VTE by overcoming many disadvantages of conventional anticoagulants. For primary VTE prevention in patients after total hip/knee arthroplasty, rivaroxaban, apixaban, and dabigatran are preferred over LMWHs, due to comparable efficacy and safety, but favourable acceptability (avoided everyday injections). In other high-risk populations (other surgical patients, acutely ill medical patients), LMWHs are still the recommended option. Betrixaban is currently the only DOAC approved for VTE prophylaxis in medically ill patients during and after hospitalization. For acute VTE treatment and secondary prevention, DOACs (rivaroxaban, apixaban, edoxaban, and dabigatran) are recommended as the first-line therapy in the general population. DOACs proved to be similarly effective but safer than VKAs. In some specific populations, DOACs also seem to be advantageous over conventional treatment (patients with renal impairment, elderly, long-term secondary prevention in cancer patients). Currently, there is no data from randomized head-to-head comparative studies between the DOAC classes or representatives so the choice is made mainly according to patient characteristics and pharmacokinetic properties of the drug.

scholarly journals Optimal duration of anticoagulant therapy in patients with venous thromboembolism

2018 ◽  
Vol 12 (4) ◽  
pp. 235-244
Author(s):  
Gualtiero Palareti
Keyword(s):  
Venous Thromboembolism ◽  
High Risk ◽  
Anticoagulant Therapy ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Severe Disease ◽  
Direct Oral Anticoagulants ◽  
Late Complications ◽  
Risk Of Recurrence ◽  
Risk Of Bleeding

Venous thromboembolism, a frequent and severe disease, has clinically important early and late complications and a strong tendency to recur. Anticoagulant therapy is the mainstay of treatment, performed by immediate administration of: i) parenteral anticoagulants followed by vitamin K antagonists, either dabigatran or edoxaban, two direct oral anticoagulants (DOACs); or ii) direct rivaroxaban or apixaban, two DOACs that can be used as single-drug approach. Treatment should last no less than 3 months in all patients though how long it should last thereafter is a more complex issue. The risk of recurrence results from several event- or patient-associated factors. Some patients have low risk and may be treated for 3 to 6 months only. Others (the majority) have a high risk of recurrence (approximately 50% in 10 years). Unfortunately, the protective effect of anticoagulation against recurrence is present only during treatment and is lost when therapy is stopped. For this reason, international guidelines recommend that there is no pre-definite period of anticoagulation (e.g. 1 or 2 years, and so on) in patients at high risk and suggest instead indefinite (extended) anticoagulation, provided there is no high risk of bleeding. When the decision is difficult, adjunctive criteria may be adopted, such as male sex and abnormal D-dimer assessed after anticoagulation is stopped, to identify patients at high risk who need indefinite therapy. The use of DOACs, especially at lower doses with a lower risk of bleeding, may make indefinite anticoagulation for patients easier.

scholarly journals Is there a role for low-dose DOACs as prophylaxis?

Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 187-193 ◽  
Author(s):  
Alexander T. Cohen ◽  
Beverley J. Hunt
Keyword(s):  
Secondary Prevention ◽  
Low Dose ◽  
Standard Dose ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Risk ◽  
Secondary Prophylaxis ◽  
Medical Patients ◽  
Vascular Events

Abstract The direct oral anticoagulants (DOACs) have transformed the management of thrombotic disorders. Large clinical trials have demonstrated that DOACs can replace vitamin K antagonists (VKAs) in the 2 existing major indications for anticoagulation: the prevention of stroke in atrial fibrillation and the acute treatment and secondary prevention of venous thromboembolism (VTE); this literature is widely known. In this article, we will concentrate on the less well-discussed benefits of the use of DOACs—using low doses as primary and secondary prophylaxis in both venous and arterial thromboprophylaxis. The attractiveness of using a low-dose DOAC is that the bleeding risk seems to be slightly lower than with the standard dose and significantly lower than with VKAs so that they can be used safely for long periods, where previously, VKAs had risk/benefit ratios that did not permit this. We discuss in detail the extended use of low-dose DOACs in secondary VTE prevention. We also cover the utility of low-dose DOACs in the evolving fields of prevention of hospital-associated VTE in acutely ill medical patients, after total hip and knee replacement, and in cancer patients. To complete the indications, we briefly discuss the role of low-dose DOACs in the secondary prevention of arterial vascular events.

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.

scholarly journals Effectiveness and Safety of Apixaban for Treatment of Venous Thromboembolism in Daily Practice

TH Open ◽  
2020 ◽  
Vol 04 (02) ◽  
pp. e119-e126 ◽  
Author(s):  
Stephan V. Hendriks ◽  
Frederikus A. Klok ◽  
Wilhelmina J.E. Stenger ◽  
Albert T.A. Mairuhu ◽  
Jeroen Eikenboom ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Daily Practice ◽  
Phase Iii ◽  
Comparable Efficacy ◽  
Phase 3 ◽  
Recurrent Vte

Abstract Introduction Phase 3 trials have shown comparable efficacy of direct oral anticoagulants (DOACs) and vitamin K antagonists in patients with acute venous thromboembolism (VTE), with less major bleeding events in patients randomized to DOAC treatment. With DOACs being increasingly used in clinical practice, evaluation of the DOACs in daily practice-based conditions is needed to confirm their safety and effectiveness. The aim of this study is to evaluate the effectiveness and safety of apixaban in VTE patients in daily practice. Methods In this retrospective cohort study, consecutive patients diagnosed with VTE in two Dutch hospitals (Leiden University Medical Center, Leiden and Haga Teaching Hospital, The Hague) were identified based on administrative codes. We assessed recurrent VTE, major bleeding and mortality during a 3-month follow-up period in those treated with apixaban. Results Of 671 consecutive VTE patients treated with apixaban, 371 presented with acute pulmonary embolism (PE) and 300 patients with deep-vein thrombosis. During 3 months treatment, 2 patients had a recurrent VTE (0.3%; 95% confidence interval [CI]: 0.08–1.1), 12 patients had major bleeding (1.8%; 95% CI: 1.0–3.2), and 11 patients died (1.6%; 95% CI: 0.9–2.9), of which one patient with recurrent PE and one because of a intracerebral bleeding. Conclusion In this daily practice-based cohort, apixaban yielded a low incidence of recurrent VTE, comparable to the phase 3 AMPLIFY study patients. The incidence of major bleeding was higher than in the AMPLIFY-study patients, reflecting the importance of daily practice evaluation and the fact that results from phase III clinical studies cannot be directly extrapolated toward daily practice.

scholarly journals Optimal duration of anticoagulant therapy in patients with venous thromboembolism

2018 ◽  
Author(s):  
Gualtiero Palareti
Keyword(s):  
Venous Thromboembolism ◽  
High Risk ◽  
Anticoagulant Therapy ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Severe Disease ◽  
Direct Oral Anticoagulants ◽  
Late Complications ◽  
Risk Of Recurrence ◽  
Risk Of Bleeding

Venous thromboembolism (VTE), a frequent and severe disease, has clinically important early and late complications and a strong tendency to recur. Anticoagulant therapy is the mainstay of treatment, performed by immediate administration of: a) parenteral anticoagulants followed by vitamin K antagonists (VKAs), either dabigatran or edoxaban, two direct oral anticoagulants (DOACs); or b) direct rivaroxaban or apixaban, two DOACs that can be used as single-drug approach. Treatment should last no less than 3 months in all patients though how long it should last thereafter is a more complex issue. The risk of recurrence results from several event- or patient-associated factors. Some patients have low risk and may be treated for 3 to 6 months only. Others (the majority), have a high risk of recurrence (approximately 50% in 10 years). Unfortunately, the protective effect of anticoagulation against recurrence is present only during treatment and is lost when therapy is stopped. For this reason, international guidelines recommend there be no pre-definite period of anticoagulation (e.g. 1 or 2 years, and so on) in patients at high risk and suggest instead indefinite (extended) anticoagulation, provided there is no high risk of bleeding. When the decision is difficult, adjunctive criteria may be adopted, such as male sex and abnormal Ddimer assessed after anticoagulation is stopped, to identify patients at high risk who need indefinite therapy. The use of DOACs, especially at lower doses with a lower risk of bleeding, may make indefinite anticoagulation for patients easier.

scholarly journals Direct Oral Anticoagulants in Nonvalvular Atrial Fibrillation: Practical Considerations on the Choice of Agent and Dosing

Cardiology ◽  
2018 ◽  
Vol 140 (2) ◽  
pp. 126-132 ◽  
Author(s):  
Dimitrios Farmakis ◽  
Periklis Davlouros ◽  
Gregory Giamouzis ◽  
George Giannakoulas ◽  
Athanasios Pipilis ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Comparable Efficacy ◽  
Thrombin Inhibitor ◽  
Systemic Embolism ◽  
Nonvalvular Atrial Fibrillation ◽  
Clinical Scenarios

Direct or new oral anticoagulants (NOACs), including the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, have recently revolutionized the field of antithrombotic therapy for stroke and systemic embolism prevention in nonvalvular atrial fibrillation (NVAF). Randomized controlled trials have shown that these agents have at least comparable efficacy with vitamin K antagonists along with superior safety, at least in what concerns intracranial hemorrhage. As a result, NOACs are indicated as first-line anticoagulation therapy for NVAF patients with at least one risk factor for stroke or systemic embolism. The rapid introduction, however, of NOACs in a field dominated for decades by vitamin antagonists and the variety of agents and dosing schemes may create difficulties in decision making. In the present article, we attempt to determine a practical approach to the choice of agent and dose in different clinical scenarios by considering not only the results of seminal randomized trials and post hoc analyses but also data from real-world patient populations as well as the recently available possibility of rapid NOAC reversal.

scholarly journals Direct oral anticoagulants: A new chapter in anticoagulation therapy

2020 ◽  
Vol 70 (5) ◽  
pp. 249-268
Author(s):  
Radica Stepanović-Petrović ◽  
Katarina Nastić
Keyword(s):  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Cardiac Biomarkers ◽  
Bleeding Complications ◽  
Comparable Efficacy ◽  
Thrombin Inhibitor ◽  
Severe Bleeding ◽  
Coronary Syndrome

Thromboembolic events are the leading cause of morbidity and mortality worldwide. From the second half of the 20th century, vitamin K antagonists (VKAs), warfarin and acenocoumarol, were the only anticoagulants taken orally. The major reform in anticoagulation therapy was made by the advent of direct oral anticoagulants (DOACs), about 10 years ago. Direct thrombin inhibitor (dabigatran) and direct inhibitors of factor Xa (rivaroxaban, apixaban, edoxaban, and betrixaban) have demonstrated favorable risk/benefit ratio. Compared to warfarin, DOACs are associated with a predictable pharmacokinetic profile, lower severe bleeding complications, particularly intracranial hemorrhages, and minimal drug interactions. Moreover, DOACs achieve a rapid onset of action and have shown comparable efficacy with warfarin and low molecular weight heparin (LMWH) in clinical trials. As a result, DOACs are now replacing VKAs and LMWH for many indications including stroke and systemic embolism prevention in nonvalvular atrial fibrillation, prevention, and treatment of venous thromboembolism and thromboprophylaxis following total knee/hip replacement surgery. In addition, rivaroxaban (in combination with aspirin alone or aspirin and clopidogrel) is used in the prevention of atherothrombotic events following acute coronary syndrome with elevated cardiac biomarkers. In case of severe bleeding complications under DOACs treatment, antidotes are available; idarucizumab for dabigatran reversal and andexanet alfa for rivaroxaban and apixaban.

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.

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.

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