23
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Expanding use of new oral anticoagulants

      review-article
      F1000Prime Reports
      Faculty of 1000 Ltd

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Related collections

          Most cited references25

          • Record: found
          • Abstract: found
          • Article: not found

          Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

          VTE is a serious, but decreasing complication following major orthopedic surgery. This guideline focuses on optimal prophylaxis to reduce postoperative pulmonary embolism and DVT. The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. In patients undergoing major orthopedic surgery, we recommend the use of one of the following rather than no antithrombotic prophylaxis: low-molecular-weight heparin; fondaparinux; dabigatran, apixaban, rivaroxaban (total hip arthroplasty or total knee arthroplasty but not hip fracture surgery); low-dose unfractionated heparin; adjusted-dose vitamin K antagonist; aspirin (all Grade 1B); or an intermittent pneumatic compression device (IPCD) (Grade 1C) for a minimum of 10 to 14 days. We suggest the use of low-molecular-weight heparin in preference to the other agents we have recommended as alternatives (Grade 2C/2B), and in patients receiving pharmacologic prophylaxis, we suggest adding an IPCD during the hospital stay (Grade 2C). We suggest extending thromboprophylaxis for up to 35 days (Grade 2B). In patients at increased bleeding risk, we suggest an IPCD or no prophylaxis (Grade 2C). In patients who decline injections, we recommend using apixaban or dabigatran (all Grade 1B). We suggest against using inferior vena cava filter placement for primary prevention in patients with contraindications to both pharmacologic and mechanical thromboprophylaxis (Grade 2C). We recommend against Doppler (or duplex) ultrasonography screening before hospital discharge (Grade 1B). For patients with isolated lower-extremity injuries requiring leg immobilization, we suggest no thromboprophylaxis (Grade 2B). For patients undergoing knee arthroscopy without a history of VTE, we suggest no thromboprophylaxis (Grade 2B). Optimal strategies for thromboprophylaxis after major orthopedic surgery include pharmacologic and mechanical approaches.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Natural history of venous thromboembolism.

            Most deep vein thromboses (DVTs) start in the calf, and most probably resolve spontaneously. Thrombi that remain confined to the calf rarely cause leg symptoms or symptomatic pulmonary embolism (PE). The probability that calf DVT will extend to involve the proximal veins and subsequently cause PE increases with the severity of the initiating prothrombotic stimulus. Although acute venous thromboembolism (VTE) usually presents with either leg or pulmonary symptoms, most patients have thrombosis at both sites at the time of diagnosis. Proximal DVTs resolve slowly during treatment with anticoagulants, and thrombi remain detectable in half of the patients after a year. Resolution of DVT is less likely in patients with a large initial thrombus or cancer. About 10% of patients with symptomatic DVTs develop severe post-thrombotic syndrome within 5 years, and recurrent ipsilateral DVT increases this risk. About 10% of PEs are rapidly fatal, and an additional 5% cause death later, despite diagnosis and treatment. About 50% of diagnosed PEs are associated with right ventricular dysfunction, which is associated with a approximately 5-fold greater in-hospital mortality. There is approximately 50% resolution of PE after 1 month of treatment, and perfusion eventually returns to normal in two thirds of patients. About 5% of treated patients with PE develop pulmonary hypertension as a result of poor resolution. After a course of treatment, the risk of recurrent thrombosis is higher (ie, approximately 10% per patient-year) in patients without reversible risk factors, in those with cancer, and in those with prothrombotic biochemical abnormalities such as antiphospholipid antibodies and homozygous factor V Leiden.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa.

              Inhibitors of coagulation factor Xa (fXa) have emerged as a new class of antithrombotics but lack effective antidotes for patients experiencing serious bleeding. We designed and expressed a modified form of fXa as an antidote for fXa inhibitors. This recombinant protein (r-Antidote, PRT064445) is catalytically inactive and lacks the membrane-binding γ-carboxyglutamic acid domain of native fXa but retains the ability of native fXa to bind direct fXa inhibitors as well as low molecular weight heparin-activated antithrombin III (ATIII). r-Antidote dose-dependently reversed the inhibition of fXa by direct fXa inhibitors and corrected the prolongation of ex vivo clotting times by such inhibitors. In rabbits treated with the direct fXa inhibitor rivaroxaban, r-Antidote restored hemostasis in a liver laceration model. The effect of r-Antidote was mediated by reducing plasma anti-fXa activity and the non-protein bound fraction of the fXa inhibitor in plasma. In rats, r-Antidote administration dose-dependently and completely corrected increases in blood loss resulting from ATIII-dependent anticoagulation by enoxaparin or fondaparinux. r-Antidote has the potential to be used as a universal antidote for a broad range of fXa inhibitors.
                Bookmark

                Author and article information

                Contributors
                Journal
                F1000Prime Rep
                F1000Prime Rep
                F1000Prime Reports
                Faculty of 1000 Ltd
                2051-7599
                01 October 2014
                2014
                : 6
                : 93
                Affiliations
                Departments of Medicine and Biochemistry and Biomedical Sciences, McMaster University and the Thrombosis and Atherosclerosis Research Institute 237 Barton Street East, Hamilton, ON, L8L 2X2Canada
                Article
                93
                10.12703/P6-93
                4191267
                69fcf21b-77e0-41f0-b246-9b28b94d4b9d
                © 2014 Faculty of 1000 Ltd

                All F1000Prime Reports articles are distributed under the terms of the Creative Commons Attribution-Non Commercial License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Review Article

                Comments

                Comment on this article