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

2018 ◽  
Vol 12 (4) ◽  
pp. 235-244
Author(s):  
Gualtiero Palareti

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.

Author(s):  
Gualtiero Palareti

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.


2019 ◽  
Vol 15 (1) ◽  
pp. 49-53
Author(s):  
V. I. Petrov ◽  
O. V. Shatalova ◽  
A. S. Gerasimenko ◽  
V. S. Gorbatenko

Aim. To study the frequency of prescribing antithrombotic agents in patients with non-valvular atrial fibrillation (AF) who were hospitalized in the cardiology department of a multidisciplinary hospital.Material and methods. A retrospective one-time study of medical records of 765 patients with non-valvular AF treated in the cardiology department of a multidisciplinary hospital in 2012 and 2016 was performed.Results. All patients were stratified in three groups depending on the CHA2DS2-VASc score. The frequency of prescribing antithrombotic agents was evaluated in each group. A low risk of thromboembolic complications was found in 1% (n=3) of patients in 2012 and 0.6% (n=3) in 2016. All these patients received antithrombotic agents. CHA2DS2-VASc=1 was found in 6% (n=15) of patients with AF in 2012 and in 3.4% (n=17) in 2016. A significant number of patients in this group received anticoagulant therapy with vitamin K antagonists (warfarin) or with direct oral anticoagulants. A high risk of thromboembolic complications (CHA2DS2-VASc≥2) was found in 93% of patient (n=245) in 2012 and in 96% (n=482) in 2016. Anticoagulant therapy was prescribed in 70.2% (n=172) patients with high risk in 2012 and 80% (n=387) in 2016. However, some patients with high risk of thromboembolic complications did not have the necessary therapy.Conclusion. Positive changes in the structure and frequency of prescribing anticoagulant drugs in patients with AF and a high risk of thromboembolic complications were found during the years studied. 


2019 ◽  
Vol 119 (05) ◽  
pp. 689-694 ◽  
Author(s):  
Jeffrey Weitz ◽  
Noel Chan

Many patients with venous thromboembolism (VTE) are at risk of recurrence if anticoagulant therapy is stopped. Whereas 3 months of anticoagulation treatment is sufficient for patients with VTE provoked by major surgery or trauma, in many cases a longer course is needed. Extended therapy with vitamin K antagonists (VKAs) requires frequent coagulation monitoring and dose adjustments to ensure that the international normalized ratio (INR) remains within the therapeutic range; furthermore, there is a risk of major bleeding even if a therapeutic INR is maintained. Therefore, more convenient and safer anticoagulants are needed.The non-VKA oral anticoagulants (NOACs)—apixaban, dabigatran, edoxaban and rivaroxaban—simplify extended therapy because they can be given in fixed doses without routine coagulation monitoring. Randomized clinical trials have demonstrated the efficacy and safety of NOACs for extended VTE treatment, but bleeding remains a concern. Patients and physicians may, therefore, be reluctant to continue anticoagulation beyond 3 to 6 months except in patients at high risk of recurrence. Acetylsalicylic acid (ASA) is often prescribed instead of an anticoagulant because of its perceived lower risk of bleeding; however, the recent EINSTEIN CHOICE trial demonstrated that once-daily rivaroxaban at a dose of either 20 or 10 mg reduced the risk of recurrent VTE by 70% compared with ASA without significantly increasing the risk of bleeding. In this review, we discuss the EINSTEIN CHOICE trial in the context of previous trials for extended VTE treatment and examine some of the lessons that can be applied to clinical practice.


2020 ◽  
Vol 70 (5) ◽  
pp. 284-296
Author(s):  
Maja Tomić

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.


VASA ◽  
2017 ◽  
Vol 46 (2) ◽  
pp. 87-95 ◽  
Author(s):  
Giovanna Elmi ◽  
Giuseppe Di Pasquale ◽  
Raffaele Pesavento

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.


Applied Nano ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 98-117
Author(s):  
Yuri B. G. Patriota ◽  
Luíse L. Chaves ◽  
Evren H. Gocke ◽  
Patricia Severino ◽  
Mônica F. R. Soares ◽  
...  

Heparin-based delivery systems have been explored to improve their therapeutic efficacy and to reduce toxicity for different administration routes. Regardless of the applied drug delivery system (DDS), the evaluation of anticoagulant performance is instrumental for the development of a suitable DDS. The understanding of the range of anticoagulant assays, together with their key applications and limitations, is essential both within the context of scientific research and for clinical usage. This review provides an overview of the current anticoagulant therapy and discusses the advantages and limitations of currently available anticoagulant assays. We also discuss studies involving low-molecular-weight heparin (LMWH)-based nanocarriers with emphasis on their anticoagulation performance. Conventional anticoagulants have been used for decades for the treatment of many diseases. Direct oral anticoagulants have overcome some limitations of heparins and vitamin K antagonists. However, the lack of an accurate laboratory assessment, as well as the lack of a factor “xaban” (Xa) inhibitor reversal agent, remains a major problem associated with these anticoagulants. LMWHs represent anticoagulant agents with noteworthy efficacy and safety, and they have been explored to improve their outcomes with various nanocarriers through several administration routes. The main problems related to LMWHs have been surmounted, and improved efficiency may be achieved through the use of DDSs.


2018 ◽  
Vol 33 (3) ◽  
pp. 356-363
Author(s):  
Samantha M. Vogel ◽  
Leticia V. Smith ◽  
Evan J. Peterson

Objective: To review evidence behind anticoagulants in cancer-associated venous thromboembolism (VTE) with a focus on low-molecular-weight heparins (LMWH) and the role of direct oral anticoagulants (DOACs). Data Sources: PubMed was searched using terms “venous thromboembolism,” “cancer,” and “anticoagulation.” This search was restricted to clinical trials, meta-analyses, and subgroup analyses. Additional references were identified from reviewing literature citations. Study Selection: English-language prospective and retrospective studies assessing the efficacy and safety of LMWH and DOACs in patients with cancer. Data Analysis: Several trials were analyzed that compared anticoagulation therapies for prevention of recurrent VTE in patients with cancer. Many studies comparing LMWH and vitamin K antagonists (VKAs) found nonsignificant differences between therapies. A single study demonstrated that LMWHs are superior to VKAs. This evidence supporting LMWH for long-term VTE treatment in patients with cancer is based on comparison to VKA, but results are limited by methodological issues, and the benefit of LMWH may be driven by poor control. Subanalyses of DOAC trials suggest these are equally or more effective as VKA in cancer, but this conclusion is underpowered. Conclusion: DOACs have the potential to bypass many challenges with traditional therapy. After analyzing the evidence available, we conclude that after careful consideration of risks and benefits, use of DOACs for VTE treatment are a reasonable option in patients with cancer.


2020 ◽  
Vol 25 (5) ◽  
pp. 391-398
Author(s):  
Fabiana Lucà ◽  
Simona Giubilato ◽  
Stefania Angela Di Fusco ◽  
Angelo Leone ◽  
Stefano Poli ◽  
...  

Antithrombotic drugs, which include antiplatelets and anticoagulants, are effective in prevention and treatment of many cardiovascular disorders such as acute coronary syndromes, stroke, and venous thromboembolism and are among the drugs most commonly prescribed worldwide. The advent of direct oral anticoagulants, which are safer alternatives to vitamin K antagonists and do not require laboratory monitoring, has revolutionized the treatment of nonvalvular atrial fibrillation and venous thromboembolism. The combination of oral anticoagulant and antiplatelet therapy is required in many conditions of great clinical impact such as the coexistence of atrial fibrillation and coronary artery disease, with indication to percutaneous coronary intervention. However, strategies that combine anticoagulant and antiplatelet therapies lead to a significant increase in bleeding rates and it is crucial to find the right combination in the single patient in order to optimize the ischemic and bleeding risk. The aim of this review is to explore the evidence and controversies regarding the optimal combination of anticoagulant and antiplatelet therapy through the consideration of past dogmas and new perspectives from recent clinical trials and to propose a tailored therapeutic approach, according to specific clinical scenarios and individual patient characteristics. In particular, we separately explored the clinical settings of stable and acute coronary syndromes and percutaneous revascularization in patients with atrial fibrillation.


TH Open ◽  
2019 ◽  
Vol 03 (01) ◽  
pp. e67-e76 ◽  
Author(s):  
Juan López-Núñez ◽  
Ricard Pérez-Andrés ◽  
Pierpaolo Di Micco ◽  
Sebastian Schellong ◽  
Covadonga Gómez-Cuervo ◽  
...  

Background The efficacy and safety of the direct oral anticoagulants (DOACs) in fragile patients (age ≥ 75 years and/or creatinine clearance levels ≤ 50 mL/min and/or body weight ≤ 50kg) with venous thromboembolism (VTE) has not been evaluated. Methods We used the RIETE database to compare the rates of the composite of VTE recurrences or major bleeding during anticoagulation in fragile patients with VTE, according to the use of DOACs or standard anticoagulant therapy. Results From January 2013 to April 2018, 24,701 patients were recruited. Of these, 10,054 (41%) were fragile. Initially, 473 fragile patients (4.7%) received DOACs and 8,577 (85%) low-molecular-weight heparin (LMWH). For long-term therapy, 1,298 patients (13%) received DOACs and 5,038 (50%) vitamin K antagonists (VKAs). Overall, 95 patients developed VTE recurrences and 262 had major bleeding. Patients initially receiving DOACs had a lower rate of the composite outcome (hazard ratio [HR]: 0.32; 95% confidence interval [CI]: 0.08–0.88) than those on LMWH. Patients receiving DOACs for long-term therapy had a nonsignificantly lower rate of the composite outcome (HR: 0.70; 95% CI: 0.46–1.03) than those on VKAs. On multivariable analysis, patients initially receiving DOACs had a nonsignificantly lower risk for the composite outcome (HR: 0.36; 95% CI: 0.11–1.15) than those on LMWH, while those receiving DOACs for long-term therapy had a significantly lower risk (HR: 0.61; 95% CI: 0.41–0.92) than those on VKAs. Conclusions Our data suggest that the use of DOACs may be more effective and safe than standard therapy in fragile patients with VTE, a subgroup of patients where the risk for bleeding is particularly high.


Blood ◽  
2020 ◽  
Vol 136 (19) ◽  
pp. 2133-2142
Author(s):  
Saskia Middeldorp ◽  
Wessel Ganzevoort

Abstract One to 2 pregnant women in 1000 will experience venous thromboembolism (VTE) during pregnancy or postpartum. Pulmonary embolism (PE) is a leading cause of maternal mortality, and deep vein thrombosis leads to maternal morbidity, with postthrombotic syndrome potentially diminishing quality of life for a woman’s lifetime. However, the evidence base for pregnancy-related VTE management remains weak. Evidence-based guideline recommendations are often extrapolated from nonpregnant women and thus weak or conditional, resulting in wide variation of practice. In women with suspected PE, the pregnancy-adapted YEARS algorithm is safe and efficient, rendering computed tomographic pulmonary angiography to rule out PE unnecessary in 39%. Low molecular weight heparin (LMWH) in therapeutic doses is the treatment of choice during pregnancy, and anticoagulation (LMWH or vitamin K antagonists [VKAs]) should be continued until 6 weeks after delivery, with a 3-month minimum total duration. LMWH or VKA use does not preclude breastfeeding. Postpartum, direct oral anticoagulants are an option if a woman does not breastfeed and long-term use is intended. Management of delivery, including type of analgesia, requires a multidisciplinary approach and depends on local preferences and patient-specific conditions. Several options are possible, including waiting for spontaneous delivery with temporary LMWH interruption. Prophylaxis for recurrent VTE prevention in subsequent pregnancies is indicated in most women with a history of VTE.


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