Blog
About

  • Record: found
  • Abstract: found
  • Article: found
Is Open Access

DOACs – advances and limitations in real world

Thrombosis Journal

BioMed Central

The 9th Congress of the Asian-Pacific Society on Thrombosis and Hemostasis (2016 APSTH)

6-9 October 2016

Oral anticoagulation, Atrial fibrillation, Stroke, Venous thromboembolism, Bleeding

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

      The group of new oral anticoagulants or NOACs, now termed direct oral anticoagulants or DOACs, with their favourable results from large scale phase III clinical trials, represent a major advancement and expanded armamentarium in antithrombotic therapy. Dabigatran, rivaroxaban, apixaban and edoxaban are now in clinical routine use for prevention and treatment of arterial and venous thrombotic diseases as addressed in their clinical trials. Usage of the DOACs is expected to increase as clinicians gain more experience and reassurance with data from the real world studies which are generally consistent with that from clinical trials. Development of specific antidotes in management of bleeding complications and development of coagulation assays for their plasma levels will further boost the confidence in the DOACs. Nonetheless, there are still limitations associated with the DOACs. Many patients in need of anticoagulant therapy for indications not studied in the clinical trials will not be eligible for treatment with a DOAC. Conditions where more data is required include DOACs use in the paediatric age group, patients with atrial fibrillation and valvular heart disease, thrombosis associated with the anti-phospholipid syndrome and cancer associated thrombosis. The affordability and access to these drugs may pose an issue for many patients under healthcare systems not providing for these medications. With four new anticoagulants coming onboard very quickly, the focus has shifted to the practical approach and management in real life as many clinicians are not yet familiar with the DOACs. Clinicians need to be educated on how to manage this new class for drugs, from choosing the appropriate drug to prevention and managing bleeding complications as a lack of knowledge and understanding in these drugs will lead to inappropriate use and compromise on patient safety.

      Related collections

      Most cited references 61

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

      Dabigatran versus warfarin in patients with atrial fibrillation.

      Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use. Dabigatran is a new oral direct thrombin inhibitor. In this noninferiority trial, we randomly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive, in a blinded fashion, fixed doses of dabigatran--110 mg or 150 mg twice daily--or, in an unblinded fashion, adjusted-dose warfarin. The median duration of the follow-up period was 2.0 years. The primary outcome was stroke or systemic embolism. Rates of the primary outcome were 1.69% per year in the warfarin group, as compared with 1.53% per year in the group that received 110 mg of dabigatran (relative risk with dabigatran, 0.91; 95% confidence interval [CI], 0.74 to 1.11; P<0.001 for noninferiority) and 1.11% per year in the group that received 150 mg of dabigatran (relative risk, 0.66; 95% CI, 0.53 to 0.82; P<0.001 for superiority). The rate of major bleeding was 3.36% per year in the warfarin group, as compared with 2.71% per year in the group receiving 110 mg of dabigatran (P=0.003) and 3.11% per year in the group receiving 150 mg of dabigatran (P=0.31). The rate of hemorrhagic stroke was 0.38% per year in the warfarin group, as compared with 0.12% per year with 110 mg of dabigatran (P<0.001) and 0.10% per year with 150 mg of dabigatran (P<0.001). The mortality rate was 4.13% per year in the warfarin group, as compared with 3.75% per year with 110 mg of dabigatran (P=0.13) and 3.64% per year with 150 mg of dabigatran (P=0.051). In patients with atrial fibrillation, dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of major hemorrhage. Dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage. (ClinicalTrials.gov number, NCT00262600.) 2009 Massachusetts Medical Society
        Bookmark
        • Record: found
        • Abstract: found
        • Article: not found

        Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.

        The use of warfarin reduces the rate of ischemic stroke in patients with atrial fibrillation but requires frequent monitoring and dose adjustment. Rivaroxaban, an oral factor Xa inhibitor, may provide more consistent and predictable anticoagulation than warfarin. In a double-blind trial, we randomly assigned 14,264 patients with nonvalvular atrial fibrillation who were at increased risk for stroke to receive either rivaroxaban (at a daily dose of 20 mg) or dose-adjusted warfarin. The per-protocol, as-treated primary analysis was designed to determine whether rivaroxaban was noninferior to warfarin for the primary end point of stroke or systemic embolism. In the primary analysis, the primary end point occurred in 188 patients in the rivaroxaban group (1.7% per year) and in 241 in the warfarin group (2.2% per year) (hazard ratio in the rivaroxaban group, 0.79; 95% confidence interval [CI], 0.66 to 0.96; P<0.001 for noninferiority). In the intention-to-treat analysis, the primary end point occurred in 269 patients in the rivaroxaban group (2.1% per year) and in 306 patients in the warfarin group (2.4% per year) (hazard ratio, 0.88; 95% CI, 0.74 to 1.03; P<0.001 for noninferiority; P=0.12 for superiority). Major and nonmajor clinically relevant bleeding occurred in 1475 patients in the rivaroxaban group (14.9% per year) and in 1449 in the warfarin group (14.5% per year) (hazard ratio, 1.03; 95% CI, 0.96 to 1.11; P=0.44), with significant reductions in intracranial hemorrhage (0.5% vs. 0.7%, P=0.02) and fatal bleeding (0.2% vs. 0.5%, P=0.003) in the rivaroxaban group. In patients with atrial fibrillation, rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism. There was no significant between-group difference in the risk of major bleeding, although intracranial and fatal bleeding occurred less frequently in the rivaroxaban group. (Funded by Johnson & Johnson and Bayer; ROCKET AF ClinicalTrials.gov number, NCT00403767.).
          Bookmark
          • Record: found
          • Abstract: found
          • Article: not found

          Apixaban versus warfarin in patients with atrial fibrillation.

          Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin. In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic embolism. The trial was designed to test for noninferiority, with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause. The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.27% per year in the apixaban group, as compared with 1.60% per year in the warfarin group (hazard ratio with apixaban, 0.79; 95% confidence interval [CI], 0.66 to 0.95; P<0.001 for noninferiority; P=0.01 for superiority). The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P<0.001), and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99; P=0.047). The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47% per year in the warfarin group (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P<0.001), and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P=0.42). In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality. (Funded by Bristol-Myers Squibb and Pfizer; ARISTOTLE ClinicalTrials.gov number, NCT00412984.).
            Bookmark

            Author and article information

            Affiliations
            Department of Haematology, Singapore General Hospital, 20, College Road, Academia Level 3, Singapore, 169856 Singapore
            Contributors
            Lee.lai.heng@singhealth.com.sg
            Conference
            Thromb J
            Thromb J
            Thrombosis Journal
            BioMed Central (London )
            1477-9560
            4 October 2016
            4 October 2016
            2016
            : 14
            Issue : Suppl 1 Issue sponsor : Publication of this supplement was funded by APSTH 2016. The articles have undergone the journal's standard peer review process for supplements. The Supplement Editors declare that they have no competing interests.
            5056491
            111
            10.1186/s12959-016-0111-3
            © The Author(s). 2016

            Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

            The 9th Congress of the Asian-Pacific Society on Thrombosis and Hemostasis
            2016 APSTH
            Taipei, Taiwan
            6-9 October 2016
            Categories
            Review
            Custom metadata
            © The Author(s) 2016

            Comments

            Comment on this article