Clinical pre‐test of a computerised antithrombotic risk assessment tool for stroke prevention in atrial fibrillation patients: giving consideration to NOACs
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Abstract Rationale, aims and objectives The decision‐making around antithrombotics in atrial fibrillation requires comprehensive risk versus benefit assessment. In view of the availability of novel oral anticoagulants (NOACs) including dabigatran, rivaroxaban and apixaban, a decision support tool designed to assist the selection of antithrombotics has been modified to consider both warfarin and NOACs. This study aims to pre‐test this modified decision support tool. Methods The decision support tool was modified to consider either warfarin or NOACs as first‐line therapy and applied to data pertaining to a cohort of 393 patients in New South Wales. Results Overall, 380 (96.7%) patients were eligible for oral anticoagulants. In the scenario of warfarin being recommended as first‐line therapy, the Computerised Antithrombotic Risk Assessment Tool version 2.0 ( caratv2.0 ) recommended warfarin for 360 (91.6%) patients, any NOAC for 5 (1.3%) patients, either rivaroxaban or apixaban for 6 (1.5%) patients and apixaban for 9 (2.2%) patients. In the scenario of NOACs as first‐line therapy, caratv2.0 recommended any NOAC for 279 (70.9%) patients, either rivaroxaban or apixaban for 80 (20.4%) patients, apixaban for 9 (2.3%) patients and warfarin for 12 (3.1%) patients. Key reasons for caratv2.0 to recommend a change from warfarin (patients' current therapy) to NOACs included known warfarin allergy/adverse reaction, a history of intracranial bleeding, and previous gastrointestinal bleeding. Key predictors for caratv2.0 to consider that patients are more suitable for NOACs over warfarin were a diagnosis of other gastrointestinal diseases, more co‐morbidities and high risk of falls. Conclusions According to this decision support tool, both warfarin and NOACs are viable treatment options in majority of the patients, but there is a scope for better rationalization of therapy.Keywords:
Apixaban
Gastrointestinal bleeding
New, non-vitamin K antagonist oral anticoagulants (NOACs) have been developed to overcome the limitations of warfarin. These include dabigatran, which inhibits thrombin, and rivaroxaban, apixaban, and edoxaban, which inhibit factor Xa. In the US, rivaroxaban and apixaban are licensed for thromboprophylaxis after elective hip or knee arthroplasty, and rivaroxaban and dabigatran are approved for treatment of venous thromboembolism. Dabigatran, rivaroxaban, and apixaban also are licensed for stroke prevention in eligible patients with atrial fibrillation. Designed to be given in fixed doses without routine coagulation monitoring, the NOACs are more convenient to administer than warfarin. Phase III clinical trials have shown that the NOACs are at least as effective as warfarin and are associated with less intracranial bleeding. This article compares the pharmacological properties of the NOACs with those of warfarin, describes the clinical trial data with the NOACs in the approved indications, outlines the unmet medical needs that the NOACs address, highlights the potential limitations of the NOACs, and provides guidance on the optimal use of the NOACs.
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There are presently new oral anticoagulants (NOAC) for prevention and the treatment of thromboembolic diseases and they are registered in CZ. It concerns of orally direct inhibitors of thrombin (dabigatran etexilate), inhibitors of factor Xa (apixaban, rivaroxaban), respectively, with advantage of some properties not being seen in "classical" anticoagulants. In the use of new anticoagulants, however, are some problems - such as laboratory monitoring in urgent situations of effective treatment and the absence of specific antidote - resolved. The text below brings indications, dosage of the drugs, their elimination, follow-up of efficacy of the treatment or risk of the bleeding as well as the therapy of bleeding complications.Key words: apixaban - dabigatran etexilate - NOAC - rivaroxaban.
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Novel oral anticoagulants (OACs), including dabigatran etexilate, rivaroxaban, and apixaban, are available alternative anticoagulant therapy to vitamin K antagonists. The US Food and Drug Administration (FDA) has approved dabigatran, rivaroxaban, and apixaban for the treatment of appropriate patients for specific clinical indications. Therapeutic advantages of prescribing the new OACs are related to their predictable pharmacokinetic and pharmacodynamic properties. Dabigatran, rivaroxaban, and apixaban have all been shown to be noninferior to warfarin treatment for stroke prevention in respective phase 3 clinical trials; dabigatran and apixaban were shown to be superior to warfarin as preventive therapy. Dabigatran, rivaroxaban, and apixaban are all approved agents for stroke prevention in patients with nonvalvular atrial fibrillation in the United States and Europe. Among these agents, rivaroxaban is the only FDA-approved drug for the treatment of venous thromboembolism. This article reviews the major clinical trials that investigated the efficacy and safety of the new OACs and the use of these agents in special clinical situations.
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Dabigatran, rivaroxaban and apixaban are oral anticoagulants used to prevent or treat thrombosis in a variety of situations. Like all anticoagulants, these drugs can provoke bleeding. How should patients be managed if bleeding occurs during dabigatran, rivaroxaban or apixaban therapy? How can the risk of bleeding be reduced in patients who require surgery or other invasive procedures? To answer these questions, we reviewed the available literature, using the standard Prescrire methodology. In clinical trials, warfarin, enoxaparin, dabigatran, rivaroxaban and apixaban were associated with a similar frequency of severe bleeding. Numerous reports of severe bleeding associated with dabigatran have been recorded since this drug was first marketed. Some situations are associated with a particularly high bleeding risk, including: even mild renal failure, advanced age, extremes in body weight and drug-drug interactions, particularly with antiplatelet agents (including aspirin), nonsteroidal antiinflammatory drugs, and many drugs used in cardiovascular indications. In patients treated with dabigatran, rivaroxaban or apixaban, changes in the INR (international normalised ratio) and activated partial thromboplastin time (aPTT) do not correlate with the dose. In early 2013, there is still no routine coagulation test suitable for monitoring these patients; specific tests are only available in specialised laboratories. In early 2013 there is no antidote for dabigatran, rivaroxaban or apixaban, nor any specific treatment with proven efficacy for severe bleeding linked to these drugs. Recommendations on the management of bleeding in this setting are based mainly on pharmacological parameters and on scarce experimen-Haemodialysis reduces the plasma concentration of dabigatran, while rivaroxaban and apixaban cannot be eliminated by dialysis. Prothrombin complex concentrates and recombinant activated factor VII seem to have little or no efficacy, and they carry a poorly documented risk of thrombosis. For patients undergoing surgery or other invasive procedures, clinical practice guidelines are primarily based on pharmacokinetic parameters and on extrapolation of data on vitamin K antagonists. The decision on whether or not to discontinue anticoagulation before the procedure mainly depends on the likely risk of bleeding. In patients at high risk of thrombosis, heparin can be proposed when the anticoagulant is withdrawn. In early 2013, difficulties in the management of bleeding and of situations in which there is a risk of bleeding weigh heavily in the balance of potential harm versus potential benefit of dabigatran, rivaroxaban and apixaban. When an oral anticoagulant is required, it is best to choose warfarin, a vitamin K antagonist, and the drug with which we have the most experience, except in those rare situations in which the INR cannot be maintained within the therapeutic range.
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OBJECTIVES: This study sought to perform an indirect comparison analysis of dabigatran etexilate (2 doses), rivaroxaban, and apixaban for their relative efficacy and safety against each other.BACKGROUND: Data for warfarin compared against the new oral anticoagulants (OACs) in large phase III clinical trials of stroke prevention in atrial fibrillation (AF) are now available for the oral direct thrombin inhibitor, dabigatran etexilate, in 2 doses (150 mg twice daily [BID], 110 mg BID), and the oral Factor Xa inhibitors, rivaroxaban and apixaban. A "head-to-head" direct comparison of drugs is the standard method for comparing different treatments, but in the absence of such head-to-head direct comparisons, another alternative to assess the relative effect of different treatment interventions would be to perform indirect comparisons, using a common comparator. Nonetheless, any inter-trial comparison is always fraught with major difficulties, and an indirect comparison analysis has many limitations, especially with the inter-trial population differences and thus, should not be overinterpreted.METHODS: Indirect comparison analysis was performed using data from the published trials.RESULTS: There was a significantly lower risk of stroke and systemic embolism (by 26%) for dabigatran (150 mg BID) compared with rivaroxaban, as well as hemorrhagic stroke and nondisabling stroke. There were no significant differences for apixaban versus dabigatran (both doses) or rivaroxaban; or rivaroxaban versus dabigatran 110 mg BID in preventing stroke and systemic embolism. For ischemic stroke, there were no significant differences between the new OACs. Major bleeding was significantly lower with apixaban compared with dabigatran 150 mg BID (by 26%) and rivaroxaban (by 34%), but not significantly different from dabigatran 110 mg BID. There were no significant differences between apixaban and dabigatran 110 mg BID in safety endpoints. Apixaban also had lower major or clinically relevant bleeding (by 34%) compared with rivaroxaban. When compared with rivaroxaban, dabigatran 110 mg BID was associated with less major bleeding (by 23%) and intracranial bleeding (by 54%). There were no significant differences in myocardial infarction events between the dabigatran (both doses) and apixaban.CONCLUSIONS: Notwithstanding the limitations of an indirect comparison study, we found no profound significant differences in efficacy between apixaban and dabigatran etexilate (both doses) or rivaroxaban. Dabigatran 150 mg BID was superior to rivaroxaban for some efficacy endpoints, whereas major bleeding was significantly lower with dabigatran 110 mg BID or apixaban. Only a head-to-head direct comparison of the different new OACs would fully answer the question of efficacy/safety differences between the new drugs for stroke prevention in AF.Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. PMID: 22575324
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Within the past 5 years, the oral anticoagulants rivaroxaban, apixaban, and dabigatran etexilate have been approved for the prevention of venous thromboembolism in adult patients after elective hip or knee arthroplasty in the European Union and many other countries worldwide. These agents differ from the previously available anticoagulants because they selectively and directly inhibit a single factor in the coagulation cascade—rivaroxaban and apixaban inhibit Factor Xa, and dabigatran inhibits Factor IIa (thrombin)—potentially enhancing the predictability of their anticoagulant effect. Currently, although some guidelines provide recommendations for the use of rivaroxaban, dabigatran etexilate, and apixaban in clinical practice, there are still questions regarding the optimal practical management of patients receiving these agents. This article briefly reviews the practical limitations associated with conventional anticoagulants, discusses potential issues with the practical management of the newer oral anticoagulants, and provides clinical experience from a single institution where rivaroxaban and dabigatran etexilate have been used within their approved indications.
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