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 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 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 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.

Venous thromboembolism in the elderly

Phlebologie ◽  
2016 ◽  
Vol 45 (04) ◽  
pp. 215-218
Author(s):  
C. Ploenes
Keyword(s):  
Venous Thromboembolism ◽  
Old Age ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Risk ◽  
The Elderly ◽  
Clinical Findings ◽  
Self Medication ◽  
Initial Symptoms

SummaryOld age is an independent risk factor of venous thromboembolism. Nevertheless initial symptoms are often attributed to existing cardiac or pulmonary comorbidity. Once deep thromboembolism (DTE) is in focus, the synopsis of clinical findings and anamnestic clues help to take further steps to establish or rule out the diagnosis (e.g. Wells score). Treatment consists in oral anticoagulation, either by vitamin-k-antagonists or by direct oral anticoagulants (“DOACs”). Strict compliance of patients or main caregivers is essential in both cases. Simultaneous medication of platelet-inhibitingor nonsteroidal anti-inflammatory drugs – often unknown self medication – results in a raised bleeding risk and should be avoided. If longterm anticoagulation is mandatory, a strategy of sequential dose-reduced anticoagulation can be considered, especially in the case of increased bleeding-risk. Systemic fibrinolysis of pulmonary embolism goes along with a very high bleeding risk in old age and should be performed only in case of vital circulatory depression or failure.

Pros and cons of new oral anticoagulants

Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 464-470 ◽  
Author(s):  
Kenneth A. Bauer
Keyword(s):  
Venous Thromboembolism ◽  
Vitamin K Antagonists ◽  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Rapid Onset ◽  
New Oral Anticoagulants ◽  
Therapeutic Class ◽  
Pros And Cons ◽  
Additional Agent

Abstract The availability of new oral anticoagulants (NOACs) targeting either thrombin (dabigatran etexilate) or factor Xa (rivaroxaban and apixaban) for the prevention and treatment of thrombosis has been highly anticipated. NOACs have major pharmacologic advantages over vitamin K antagonists (eg, warfarin), including rapid onset/offset of action, few drug interactions, and predictable pharmacokinetics, eliminating the requirement for regular coagulation monitoring. Regulatory agencies have approved several NOACs for specific indications based on the results of clinical trials demonstrating efficacy and safety that are at least as good, if not better, than warfarin (for stroke prevention in atrial fibrillation and treatment and secondary prevention of venous thromboembolism) or low-molecular-weight heparin, which is injectable (for initial treatment of venous thromboembolism and thromboprophylaxis in patients undergoing hip or knee arthroplasty). However, the adoption of this new therapeutic class into clinical practice has been slower than expected due to several factors including concerns regarding medication adherence without laboratory monitoring, uncertainty about dosing in some patient populations (eg, renal dysfunction, marked extremes of body weight), and higher drug costs compared with warfarin. Other issues are the current absence of specific antidotes for NOACs and assays to measure drug levels at most centers. The indications for NOACs on the market will expand and at least one additional agent (edoxaban) will likely gain approval within the next 2 years. As practitioners gain familiarity with the drugs and healthcare systems adapt to their use, NOAC use will increase substantially over time. Warfarin, however, will continue to be an appropriate anticoagulant choice for many patients.

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.

The secondary prevention of venous thromboembolism: Towards an individual therapeutic strategy

Vascular ◽  
2018 ◽  
Vol 26 (6) ◽  
pp. 670-682 ◽  
Author(s):  
Giovanna Elmi ◽  
Attilia M Pizzini ◽  
Mauro Silingardi
Keyword(s):  
Venous Thromboembolism ◽  
Secondary Prevention ◽  
Recurrent Events ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
External Validation ◽  
Bleeding Risk ◽  
Individual Risk ◽  
Risk Of Recurrence ◽  
The Individual

After the anticoagulant withdrawal, a substantial proportion of patients with venous thromboembolism will develop recurrent events. Whether to consider an extended treatment depends on the risk of recurrence and bleeding risk. The assessment of the individual risk profile remains a difficult task. Several basal and post-basal factors modulate the risk of recurrence and may help clinicians to select patients who can benefit from the extended therapy. During the year 2017, new evidence regarding the post-basal factors was provided by the Morgagni and Scope studies. Another interesting novelty was the VTE-BLEED score, the first bleeding risk score that obtained the external validation in venous thromboembolism setting. In secondary prevention, the use of direct oral anticoagulants is growing instead of vitamin K antagonist. Even at lower doses, direct oral anticoagulants showed to be effective and safe, to reduce all-cause mortality and seemed to be superior to placebo for the composite outcome of fatal bleeding and fatal recurrence. After the recently published Einstein-Choice trial, the role of aspirin has become truly marginal as rivaroxaban 10 mg showed a bleeding risk similar to aspirin 100 mg but a greater effectiveness reducing the relative risk of recurrence by about 70%. Another option for secondary prevention could be sulodexide, with a lower protective effect than direct oral anticoagulants but an interesting safety profile. In conclusion, in our opinion, an individual strategy taking into account the risk of recurrence, bleeding risk, therapeutic options and patient preferences is the most appropriate approach to secondary prevention of venous thromboembolism.

scholarly journals Recent advances in the treatment of venous thromboembolism in the era of the direct oral anticoagulants

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 985 ◽  
Author(s):  
Jeffrey I. Weitz ◽  
Iqbal H. Jaffer ◽  
James C. Fredenburgh
Keyword(s):  
Venous Thromboembolism ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Prevention Of Recurrence ◽  
Active Cancer ◽  
Routine Coagulation ◽  
Inhibit Factor

The direct oral anticoagulants (DOACs) have now supplanted vitamin K antagonists (VKAs) for the treatment of venous thromboembolism (VTE). The DOACs include dabigatran, which inhibits thrombin, and rivaroxaban, apixaban, and edoxaban, which inhibit factor Xa. The DOACs are as effective for the prevention of recurrence as conventional VTE treatment, consisting of a parenteral anticoagulant followed by a VKA, and are associated with less bleeding. Because of these properties and the convenience of fixed dosing without the need for routine coagulation monitoring, guidelines now recommend DOACs over VKAs for VTE treatment in patients without active cancer. This paper examines the increasing role of the DOACs for VTE treatment.

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