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[Contribution of novel anticoagulants fondaparinux and dabigatran to venous thromboembolism prevention].
Antonijević, N, Kanjuh, V, Živković, I, Jovanović, L, Vukčević, M, Apostolović, M
Srpski arhiv za celokupno lekarstvo. 2015;(3-4):230-6
Abstract
The data that episodes and sequels of venous thromboembolism (VTE) are recorded in a significant percentage of patients receiving standard anticoagulants as VTE prophylaxis (unfractionated, low-molecular-weight heparin and vitamin K inhibitors) as well as the fact that these drugs have significant limitations and that they may cause serious side-effects in some patients indicate the need for the introduction of new anticoagulant drugs. Fondaparinux, a selective inhibitor of Factor Xa, administered following major orthopedic surgeries having a high risk for the development of VTE, is more efficient than enoxaparin sodium used in European and North-American approved doses. The increased incidence of major bleeding (excluding fatal) due to fondaparinux could be perhaps lowered by dosage reduction in patients with a mildly decreased creatinine clearance. Dabigatran, a peroral direct thrombin inhibitor, administered for VIE prophylaxis in elective hip and knee surgery, showed in to date studies the efficacv comparable (if dabiqatran is given in both dosage regimes of 150 mg and 220 mg daily) or superior (if dabigatran is given at a dose of 220 mg daily) to enoxaparin administered in European-approved doses, while North American-approved doses of enoxaparin were superior than dabigatran in VTE reduction. No significant differences in bleeding rates were determined in any of the study groups. We consider that the introduction of new anticoagulants, including fondaparinux and dabigatran, will contribute to the establishment of a better safety profile and efficacy, and will also enable adequate therapy individualization for each patient depending on his/hers clinical characteristics. The introduction of novel peroral anticoagulants will, inter alia, significantly contribute to improvement in the quality of life, release the patient from numerous limitations in nutrition, interreaction, frequent laboratory monitoring, and also significantly improve therapeutic predictability.
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Safety and efficacy of dabigatran versus warfarin in patients undergoing catheter ablation of atrial fibrillation: a systematic review and meta-analysis.
Providência, R, Albenque, JP, Combes, S, Bouzeman, A, Casteigt, B, Combes, N, Narayanan, K, Marijon, E, Boveda, S
Heart (British Cardiac Society). 2014;(4):324-35
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Abstract
BACKGROUND Dabigatran etexilate, a new thrombin inhibitor, has been shown to be comparable to warfarin in patients with atrial fibrillation (AF). However, there is a limited body of evidence on the efficacy and safety of using dabigatran among patients undergoing AF catheter ablation. OBJECTIVE A random effects meta-analysis was performed of controlled trials comparing dabigatran and warfarin in paroxysmal/persistent AF patients undergoing catheter ablation. METHODS Data sources included Medline, Embase, and Cochrane (from inception to April 2013). Three independent reviewers selected studies comparing warfarin to dabigatran. Descriptive and quantitative information was extracted from each selected study, regarding periprocedural all cause mortality, thromboembolic events and major bleeding, as well as modalities of periprocedural anticoagulation bridging. RESULTS After a detailed screening of 228 search results, 14 studies were identified enrolling a total of 4782 patients (1823 treated with dabigatran and 2959 with warfarin). No deaths were reported. No significant differences were found between patients treated with dabigatran and warfarin as regards thromboembolic events (0.55% dabigatran vs 0.17% warfarin; risk ratios (RR)=1.78, 95% CI 0.66 to 4.80; p=0.26) and major bleeding (1.48% dabigatran vs 1.35% warfarin; RR=1.07, 95% CI 0.51 to 2.26; p=0.86). No difference was found between the 110 mg twice daily and 150 mg twice daily dabigatran dosages concerning major bleeding (0% vs 1.62%, respectively; RR=0.19, 95% CI 0.01 to 3.18; p=0.25) and thromboembolism (0% vs 0.40%, respectively; RR=0.72, 95% CI 0.04 to 12.98; p=0.82). CONCLUSIONS In the specific setting of AF catheter ablation, this first pooled analysis suggests that patients treated with dabigatran have a similar incidence of thromboembolic events and major bleeding compared to warfarin, with low event rates overall.
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Advantages and limitations of the new anticoagulants.
Schulman, S
Journal of internal medicine. 2014;(1):1-11
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Abstract
During recent years, three new anticoagulants (dabigatran, rivaroxaban and apixaban) have been introduced to the market, probably with one more anticoagulant (edoxaban) in the next 2 years. This review is not intended to compare the efficacy and risks of these new agents, but rather to detail the advantages and limitations. The pharmacokinetic characteristics of these drugs have few drug and food interactions, predictable dose responses, and rapid onset and offset, thus resulting in simplified management of the patient requiring anticoagulant therapy. No routine laboratory monitoring is required. A somewhat unexpected, but exciting observation involving the new anticoagulants, is the uniform reduction in intracranial bleeding by one-half compared with warfarin. The potential limitations of the new anticoagulants include uncertainty regarding assessment of drug levels, safe drug levels for major surgery, management of major bleeding, renal dependence, multiple dose regimens, adherence in the absence of frequent monitoring and unknown, rare side effects that were not captured in the trials. This review should clarify some of these concerns.
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The acute management of haemorrhage, surgery and overdose in patients receiving dabigatran.
Alikhan, R, Rayment, R, Keeling, D, Baglin, T, Benson, G, Green, L, Marshall, S, Patel, R, Pavord, S, Rose, P, et al
Emergency medicine journal : EMJ. 2014;(2):163-8
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Dabigatran is an oral direct thrombin inhibitor (DTI) licensed for stroke prevention in atrial fibrillation and likely to be soon approved in Europe for treatment of venous thrombosis. Predictable pharmacokinetics and a reduced risk of intracranial haemorrhage do not negate the potential risk of haemorrhage. Unlike warfarin, there is no reversal agent and measurement of the anticoagulant effect is not 'routine'. The prothrombin time/international normalised ratio response to dabigatran is inconsistent and should not be measured when assessing a patient who is bleeding or needs emergency surgery. The activated partial thromboplastin time (APTT) provides a qualitative measurement of the anticoagulant effect of dabigatran. Knowledge of the time of last dose is important for interpretation of the APTT. Commercially available DTI assays provide a quantitative measurement of active dabigatran concentration in the plasma. If a patient receiving dabigatran presents with bleeding: omit/delay next dose of dabigatran; measure APTT and thrombin time (consider DTI assay if available); administer activated charcoal, with sorbitol, if within 2 h of dabigatran ingestion; give tranexamic acid (1 g intravenously if significant bleeding); maintain renal perfusion and urine output to aid dabigatran excretion. Dabigatran exhibits low protein binding and may be removed by dialysis. Supportive care should form the mainstay of treatment. If bleeding is life/limb threatening, consider an additional haemostatic agent. There is currently no evidence to support the choice of one haemostatic agent (FEIBA, recombinant factor VIIa, prothrombin complex concentrates) over another. Choice will depend on access to and experience with available haemostatic agent(s).
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Newer oral anticoagulant agents: a new era in medicine.
Goel, R, Srivathsan, K
Current cardiology reviews. 2012;(2):158-65
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After a gap of almost 60 years following the development of warfarin, 2 new categories of oral anticoagulant agents have been approved for clinical use - the direct thrombin inhibitors and factor Xa inhibitors. These agents promise to be more convenient to administer with fixed dosing but still have equivalent efficacy and improved bleeding risk compared to warfarin. The clinical community is looking forward to the widespread usage of these agents but there is also some apprehension regarding bleeding risks, non-availability of specific reversal strategies and lack of specific monitoring parameters. This review article will attempt to educate the reader about three representative drugs from these classes: Dabigatran, Rivaroxaban and Apixaban. We will discuss the historical perspective to the development of these drugs, available research data and pharmacology of these agents. The best strategies for monitoring and reversal of these drugs in special situations will also be touched upon.
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Thromboprophylaxis in patients older than 75 years or with moderate renal impairment undergoing knee or hip replacement surgery [corrected].
Dahl, OE, Kurth, AA, Rosencher, N, Noack, H, Clemens, A, Eriksson, BI
International orthopaedics. 2012;(4):741-8
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PURPOSE Prospective, double-blind studies in orthopaedic patients have been conducted using the direct thrombin inhibitor dabigatran etexilate (hereafter referred to as dabigatran), with two doses investigated and approved for adults (220 mg and 150 mg once daily) to prevent venous thromboembolism (VTE). The European Medicines Agency decided that in major joint orthopaedic surgery, the lower dose should be used in elderly patients (aged over 75 years) and those with reduced renal function (creatinine clearance between 30 and 50 ml/min). Our objective was to understand the efficacy and bleeding data for the lower dose in this subpopulation. METHODS We extracted and analysed data from the elderly or from moderately renally impaired patients (n 632 of = 5,539) from the orthopaedic clinical development programme of dabigatran. RESULTS Dabigatran 150 mg once daily was as effective as the standard European enoxaparin regimen, with numerically fewer major bleeding events. Rates of major VTE were 4.3% vs 6.4% of patients, respectively. Major bleeding events occurred in four (1.3%) vs 11 (3.3%), which shows a trend towards lower bleeding with dabigatran 150 mg [odds ratio (OR) 0.40; 95% confidence interval (CI) 0.13-1.25; p = 0.110]. Mean volume of blood loss was 395 vs 417 ml, and transfused units were 2.4 vs 2.5, respectively. Other safety parameters, including the incidence of wound infections and complications, were similar for 150 mg once daily dabigatran and enoxaparin. CONCLUSION For patients at higher risk of bleeding, dabigatran 150 mg once daily is as effective as enoxaparin following major orthopaedic surgery and is associated with a favourable bleeding rate.
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Novel oral anticoagulation in management of venous thromboembolism, atrial fibrillation, and acute coronary syndrome.
Khemasuwan, D, Suramaethakul, N
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2012;(5):476-86
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Venous thromboembolism (VTE) is a major public health concern since the incidence of VTE rises substantially with age. Furthermore, the diagnosis can be elusive since patients can present differently, causing delay in diagnosis and initiation of treatment and resulting in major morbidity and mortality. In addition to accuracy and precision in diagnosis, antithrombotic therapies are the cornerstones of VTE management. In traditional paradigm, vitamin K antagonists (warfarin), indirect factor Xa inhibitors, and heparin are the foundation in management of VTE. Warfarin has been the only available oral anticoagulant therapy for several decades. Although warfarin is effective in both treatment and prophylaxis against VTE, there are several limitations. Therefore, the novel anticoagulation therapies, including rivaroxaban, apixaban, and dabigatran etexilate, have apparent advantages over warfarin in terms of clinical efficacy and adverse effects. The objective of this review is to describe the background and clinical implications of these novel anticoagulants.
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[New anticoagulants: dabigatran, rivaroxaban and apixaban].
Vargas Ruiz, AG, Ramírez López, AN, Medina Viramontes, ME
Gaceta medica de Mexico. 2012;(3):257-64
Abstract
To date, the most widely used drugs in our anticoagulation clinics are acenocoumarin and warfarin, which belong to the category of vitamin K antagonists (VKA). They have about 70 years of use in the clinic, with proven efficacy for various thrombotic diseases, but also with known problems of variability and dietary and drug interactions. In hospital thromboprophylaxis, the most widely used anticoagulant is enoxaparin, a low molecular weight heparin (LMWH). A new generation of anticoagulants are available, the direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban and apixaban), with obvious advantages over conventional anticoagulants. This paper summarizes what has been published to date for these new antithrombotics.
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Dabigatran as anticoagulant therapy for atrial fibrillation. Which patients should receive it, which patients may not need it, and other practical aspects of patient management.
Douketis, JD
Polskie Archiwum Medycyny Wewnetrznej. 2011;(3):73-80
Abstract
In the past decade, antithrombotic therapy research has focused on the development of new oral anticoagulant drugs to replace vitamin K antagonists for stroke prevention in patients with chronic atrial fibrillation, for preventing cardiovascular complications of acute coronary syndromes, and for the prevention and treatment of venous thromboembolism. The most anticipated studies relate to the use of new oral anticoagulants to replace vitamin K antagonists for the prevention of stroke in patients with atrial fibrillation. This review will focus on dabigatran, the first non-vitamin K anticoagulant approved for this clinical indication, and will assess the RE-LY trial (Randomized Evaluation of Long Term Anticoagulant Therapy) findings according to the level of anticoagulation control in warfarin-treated patients. The objectives of this review are: 1) to provide an overview of dabigatran, highlighting clinically relevant properties; 2) to provide a commentary on the study by Wallentin et al. within the context of how the quality of anticoagulation control affects warfarin efficacy and safety; and 3) to consider which patients with chronic atrial fibrillation should receive and which may not need to receive dabigatran.
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New anticoagulants: how to deal with treatment failure and bleeding complications.
Kazmi, RS, Lwaleed, BA
British journal of clinical pharmacology. 2011;(4):593-603
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Conventional anticoagulants have proven efficacy in the management of thromboembolism. Their adverse effects and a narrow therapeutic window, necessitating regular need for monitoring, however, have long been an incentive for the development of safer anticoagulants without compromising efficacy. Over the last decade or so several new parenteral and oral anticoagulants have been launched with efficacy comparable with conventional agents. From fondaparinux to its long acting derivative idraparinux, and the factor Xa inhibitor rivaroxaban to the direct thrombin inhibitor dabigatran, the advent of new anticoagulants is radically changing anticoagulation. For conventional anticoagulants, despite their shortcomings, effective methods of reversing their anticoagulant effects exist. Moreover, strategies to deal with the occurrence of fresh thrombotic events in the face of therapeutic anticoagulation with the conventional agents have also been addressed. Nevertheless, for the new anticoagulants, the optimal management of these complications remains unknown. This review explores these issues in the light of current evidence.