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Anticoagulation in Venous Thromboembolism Prophylaxis in Medically Ill Patients: Potential Impact of NOACs.
Knotts, TL, Mousa, SA
American journal of cardiovascular drugs : drugs, devices, and other interventions. 2019;(4):365-376
Abstract
While substantial evidence supports the use of standard-duration injectable anticoagulants for venous thromboembolism (VTE) prophylaxis, consensus is mixed about which agents may be preferred in acutely ill patients with ongoing need of VTE prophylaxis past the first 10-day duration of hospital stay and post-discharge. Non-vitamin K antagonist oral anticoagulants (NOACs) provide Factor Xa inhibition to prevent the thrombin generation essential in thromboembolism development, but evidence for the efficacy and safety of most NOACs is conflicting regarding extended-duration prophylaxis. Enoxaparin, a preferred injectable anticoagulant in standard-duration VTE prophylaxis, has shown an increased risk of major bleeding events when used in extended-duration prophylaxis, which outweighs its benefit. Rivaroxaban has demonstrated efficacy in extended-duration prophylaxis, but both rivaroxaban and apixaban have shown increased risks of major bleeding. Betrixaban remains the only NOAC approved in the USA for extended-duration VTE prophylaxis, and it demonstrates efficacy, with fewer adverse effects than other NOACs. This review evaluates the appropriateness of different NOAC agents compared with current therapies for the extended-duration VTE prophylaxis setting in medically ill populations.
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[Contemporary approaches to determine the duration of anticoagulant therapy for venous thromboembolism].
Lobastov, KV
Khirurgiia. 2019;(5):94-103
Abstract
The review is devoted to the issue of optimal duration of anticoagulant therapy for venous thromboembolic complications (VTEC) using oral anticoagulants (OAC). These drugs are characterized by higher safety in comparison with vitamin K antagonists and make it possible to increase the duration of treatment for not only spontaneous thrombosis (with high risk of recurrence), but also thrombosis provoked by minor persistent and transient risk factors of VTEC. Efficacy and safety of prolonged treatment of VTEC using OAC was analyzed. Different classifications of primary thrombotic episode depending on risk of subsequent recurrence are presented. Moreover, scales for individual assessment of risk of recurrent thrombosis after anticoagulant therapy cancellation and risk of bleeding in case of continued treatment are given. Outcomes of long-term administration of rivaroxaban for VTEC are analyzed. It was concluded that OAC are safe for prolonged management of primary thrombotic episode. However, overall duration of treatment should be determined considering individual balance of benefits and risks.
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Very elderly patients with venous thromboembolism on oral anticoagulation with VKAs or DOACs: Results from the prospective multicenter START2-Register Study.
Poli, D, Antonucci, E, Bertù, L, Vignini, E, Ruocco, L, Mastroiacovo, D, Paparo, C, Pastori, D, Testa, S, Ageno, W, et al
Thrombosis research. 2019;:28-32
Abstract
INTRODUCTION Few data are available on the safety of anticoagulation in very elderly patients treated with Vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) for venous thromboembolism (VTE). METHODS We carried out a prospective cohort study on VTE patients aged ≥85 years enrolled in the Survey on anticoagulaTed pAtients RegisTer (START2-Register) on treatment with VKAs or DOACs, with the aim to evaluate mortality, bleeding and thrombotic rates (venous and arterial). RESULTS We enrolled 272 patients, 58.7% on VKA and 41.3% on DOACs. Baseline characteristics were similar between treatment groups, with a higher prevalence of renal failure in VKAs patients and of a history of bleeding and previous stroke/TIA in DOACs patients. During follow-up of 429 patient-years, 15 major and non-major clinically relevant bleedings were recorded (rate 3.5 × 100 pt-yrs), 5 were major bleeds (rate 1.2 × 100 pt-yrs), 1 in a patient on aspirin (rate 4.3 × 100 pt-yrs). Bleeding rate was higher in patients on DOACs (crude HR 4.7; 95%CI 1.5-15.01). Eight thrombotic events were recorded (rate 1.9 × 100 pt-yrs), 3 recurrent VTE and 5 stroke/TIA. Overall, the incidence of thrombotic events was higher in DOACs patients (crude HR 4.5; 95% CI 1.5; 13.3). The rate of recurrent VTE was similar in the two group. Mortality rate was significantly lower in DOACs patients (crude HR 0.30; 95% CI 0.1;0.9). CONCLUSION A higher bleeding risk was found in very elderly VTE patients on DOACs despite the wide use of low-dosages. Similarly a higher thrombotic risk was found while the incidence of recurrent VTE was low and similar between the groups. Mortality rate were significantly lower in DOACs patients.
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4.
Editor's Choice - A Systematic Review and Meta-Analysis of the Efficacy and Safety of Anticoagulation in the Treatment of Venous Thromboembolism in Patients with Cancer.
Kirkilesis, GI, Kakkos, SK, Tsolakis, IA
European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery. 2019;(5):685-701
Abstract
OBJECTIVE/BACKGROUND The aim was to review the relative efficacy and safety of anticoagulation for managing venous thromboembolism (VTE) in patients with cancer. METHODS A systematic review and meta-analysis was carried out. On 17 May 2018 the MEDLINE and Scopus databases were searched for randomised controlled trials (RCTs). Eligible RCTs had to be performed in patients with cancer exclusively or to report results on a subset of patients with cancer. The main study outcomes (efficacy/recurrent VTE and safety/bleeding events) were expressed as risk ratios (RR) with a 95% confidence interval (CI). The quality of evidence was assessed following the GRADE method. RESULTS Twenty-three RCTs with 6980 patients were identified. Low molecular weight heparins (LMWHs) were more effective than vitamin K antagonists (VKAs) in preventing recurrent VTE (RR 0.58, 95% CI 0.45-0.75) and deep vein thrombosis (RR 0.44, 95% CI 0.29-0.69) but not pulmonary embolism (PE), bleeding, or overall mortality. Direct oral anticoagulants (DOACs) were more effective than VKAs in preventing recurrent VTE (RR 0.65, 95% CI 0.45-0.95) but not DVT, PE, overall mortality, or bleeding. However, anti-Xa DOACs were more effective (RR for VTE 0.64, 95% CI 0.42-0.97) and caused less bleeding than VKAs, although major bleeding was reduced only with DOACs not requiring initial parenteral anticoagulation (RR 0.45, 95% CI 0.21-0.97). In a direct comparison, DOACs were more effective than LMWHs in preventing VTE recurrence (RR 0.64, 95% CI 0.45-0.90) but caused more major bleeding (RR 1.75, 95% CI 1.10-2.77), with no difference in fatal bleeding and overall mortality. Quality of evidence, where sufficient, was mostly moderate or high. CONCLUSION Compared with VKAs, LMWHs and DOACs are more effective in treating VTE, but the former caused less bleeding. DOACs are more effective than LMWHs in preventing VTE recurrence but may carry a higher risk of major bleeding, pending additional information by ongoing trials.
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Anticoagulant Medications for the Prevention and Treatment of Thromboembolism.
Brien, L
AACN advanced critical care. 2019;(2):126-138
Abstract
Venous thromboembolism is a preventable medical condition associated with significant morbidity and mortality. It can lead to deep vein thrombosis, pulmonary embolism, and stroke. Thrombi develop when intravascular conditions promote activation of the coagulation system or when there is an imbalance between endogenous anticoagulants and procoagulants. Such conditions include vascular injury, inflammation, venous stasis, and hypercoagulable states. Anticoagulant medications are indicated for the prevention and treatment of venous thromboembolism. They exert their effect on clotting factors to prevent the formation of thrombi or the propagation of an existing clot. Historically, anticoagulants were limited to heparins and vitamin K antagonists. Over the past 15 years, however, several new anticoagulant medications have been introduced. This article describes commonly prescribed and newer anticoagulants available to health care professionals, including their mechanism of action, therapeutic use, unique characteristics, and available reversal agents in the event of life-threatening bleeding.
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Pathogenesis and Management of Thrombotic Disease in Myeloproliferative Neoplasms.
Arachchillage, DR, Laffan, M
Seminars in thrombosis and hemostasis. 2019;(6):604-611
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Abstract
Chronic myeloproliferative neoplasms (MPN) are characterized by clonal expansion of an abnormal hematopoietic stem/progenitor cell and include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Venous thrombosis, often at unusual sites, including splanchnic vein thrombosis and arterial thrombosis, as well as a hemorrhagic tendency and a propensity to transform into myelofibrosis or acute leukemia are common complications in patients with MPNs. The pathogenesis of thrombosis in MPN patients is complex and multifactorial. Disease related factors, such as an increase in blood cell counts (i.e., leukocytosis, erythrocytosis, and thrombocytosis), and more importantly presence of JAK2 mutation can interact with non-disease patient related factors such as age, previous history of thrombotic events, obesity, hypertension, hyperlipidemia, and presence of thrombophilic defects. The overall rate of recurrent thrombosis after venous thromboembolism (VTE) is 6.0 to 6.5 per 100 patient-years in patients with MPN compared to 2.7 to 3.7 per 100 patient-years in patients without MPN, and antithrombotic therapy with vitamin K antagonists (VKAs) is associated with a clear benefit, reducing the incidence of recurrence by 48 to 69%. Life-long oral anticoagulation with VKAs is the cornerstone of the antithrombotic treatment for splanchnic vein thrombosis (SVT). Patients with MPN-related cerebral venous thrombosis (CVT) should also be treated with long-term anticoagulation with VKAs. The role of direct acting oral anticoagulants in patients with thrombosis and MPN is not established and the use of these anticoagulants should be considered on an individual basis according to the risk of recurrent of VTE and bleeding.
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[Modern treatment of deep vein thrombosis and pulmonary embolism].
Renczes, J, Lindhoff-Last, E
Der Internist. 2019;(6):644-655
Abstract
Virchow's triad has been known for a 100 years. The development of therapeutic possibilities during this time was enormous. Today anticoagulant therapy is much more differentiated. Four new oral substances have replaced the traditional treatment with vitamin K antagonists in angiology. A standardized dosage is available. The monitoring of the coagulation parameters is no longer necessary, but it is important to monitor renal function. Direct oral anticoagulants are approved for the treatment of venous thrombosis and pulmonary embolism, but not during pregnancy or in children. Severe bleeding complications, especially intracerebral bleeding, are less common. The incidence of venous thromboembolism is still high. Obesity and cancer are of particular importance. The "therapeutic pact" with the patient requires that physicians master the art of "talking medicine".
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Betrixaban: Safely Reducing Venous Thromboembolic Events with Extended Prophylaxis.
Dobesh, PP, Trevarrow, BJ
The American journal of medicine. 2019;(3):307-311
Abstract
Although venous thromboembolism prophylaxis of acute medically ill patients is commonly employed, a percentage of high-risk patients still have venous thromboembolic events within 30 days of discharge. Research over the last several years has attempted to identify characteristics of these high-risk patients to facilitate provision of extended prophylaxis and venous thromboembolic event reduction; however, extended prophylaxis has been associated with a significant increase in the risk for major bleeding until recently. Betrixaban, a new oral direct Xa inhibitor with once-daily dosing and limited renal elimination, significantly reduces the risk of venous thromboembolism without increasing the risk for major bleeding. Consequently, betrixaban is the only anticoagulant approved by the Food and Drug Administration for preventing venous thromboembolism with extended prophylaxis in acute medically ill patients.
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Direct-Acting Oral Anticoagulants in Critically Ill Patients.
Rali, P, Gangemi, A, Moores, A, Mohrien, K, Moores, L
Chest. 2019;(3):604-618
Abstract
The direct-acting oral anticoagulants (DOACs) have been increasingly used over vitamin K antagonists in recent years because they do not require monitoring and have an immediate anticoagulation effect. In general, DOACs have exhibited a better safety profile and noninferiority for prophylaxis and treatment of venous thromboembolism (VTE) and stroke prevention in patients with atrial fibrillation compared with vitamin K antagonists in the non-ICU population; whether this finding holds true in patients who are critically ill remains unknown. The current review addresses the role of DOACs in special ICU populations, use of these agents for VTE prophylaxis, perioperative management of DOACs, drug monitoring, and potential drug interactions of DOACs in critically ill patients. Adverse events and available reversal agents for DOACs are also discussed.
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Rivaroxaban for non-valvular atrial fibrillation and venous thromboembolism in the Netherlands: a real-world data based cost-effectiveness analysis.
de Jong, LA, Gout-Zwart, JJ, van den Bosch, M, Koops, M, Postma, MJ
Journal of medical economics. 2019;(4):306-318
Abstract
BACKGROUND Non-vitamin K antagonist oral anticoagulants (NOACs) have been included in international guidelines as important alternatives to vitamin K antagonists (VKAs) for the treatment of venous thromboembolism (VTE) and stroke prevention in non-valvular atrial fibrillation (NVAF). Meanwhile, in the Netherlands, NOACs are widely used next to VKAs. The objective of this study is to estimate the cost-effectiveness of treatment with rivaroxaban compared to VKAs in NVAF and VTE patients in the Netherlands, using data from international prospective observational phase IV studies. METHODS Two models were developed to represent NVAF and VTE patients, populated with patients from the XANTUS (NCT01606995) and XALIA (NCT01619007) international prospective observational studies. The 1-year cost-effectiveness of rivaroxaban use, compared to VKAs, was explored in a population consisting of NVAF and VTE patients (base case) as well as for four scenarios with sub-populations: NVAF patients only, VTE patients only, NVAF patients with unstable international normalized ratio (INR), and NVAF patients using an INR self-measuring device. RESULTS In the base case, rivaroxaban saved €72,350 and gained 21 quality-adjusted life-years (QALYs) in a simulation of 2,000 patients over the use of VKAs. Ergo, rivaroxaban was dominant over VKAs. The probabilistic sensitivity analysis showed a probability of 85% for rivaroxaban being dominant and 100% at a willingness-to-pay threshold of €20,000/QALY. Rivaroxaban appeared to be dominant in all scenarios as well, except for the NVAF-patients-only scenario where the incremental cost-effectiveness ratio (ICER) was €157/QALY. CONCLUSIONS In patients with NVAF or VTE, rivaroxaban treatment is likely to be cost-effective and a potentially cost-saving alternative to VKA in the Netherlands.