Thromb Haemost 2015; 113(06): 1370-1377
DOI: 10.1160/TH14-10-0859
Atherosclerosis and Ischaemic Disease
Schattauer GmbH

Safety and efficacy of well managed warfarin

A report from the Swedish quality register Auricula
Vilhelm Sjögren
1   Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
,
Bartosz Grzymala-Lubanski
1   Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
,
Henrik Renlund
2   Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
,
Leif Friberg
3   Karolinska Institute and Department of Cardiology, Danderyd University Hospital, Stockholm, Sweden
,
Gregory Y. H. Lip
4   University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK
5   Aalborg Thrombosis Research Unit, department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark
,
Peter J. Svensson
6   Department for Coagulation Disorders, University of Lund, Malmö, Sweden
,
Anders Själander
1   Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
› Author Affiliations
Financial support: This study was supported by the Department of Public Health and Clinical Medicine, Umeå University and the Department of Research and Development, County Council of Vasternorrland [LVNFOU216571, 310871, 385111].
Further Information

Publication History

Received: 15 October 2014

Accepted after major revision: 10 January 2015

Publication Date:
29 November 2017 (online)

Summary

The safety and efficacy of warfarin in a large, unselected cohort of warfarin-treated patients with high quality of care is comparable to that reported for non-vitamin K antagonists. Warfarin is commonly used for stroke prevention in atrial fibrillation, as well as for treatment and prevention of venous thromboembolism. While reducing risk of thrombotic/embolic incidents, warfarin increases the risk of bleeding. The aim of this study was to elucidate risks of bleeding and thromboembolism for patients on warfarin treatment in a large, unselected cohort with rigorously controlled treatment. This was a retrospective, registry-based study, covering all patients treated with warfarin in the Swedish national anticoagulation register Auricula, which records both primary and specialised care. The study included 77,423 unselected patients with 100,952 treatment periods of warfarin, constituting 217,804 treatment years. Study period was January 1, 2006 to December 31, 2011. Atrial fibrillation was the most common indication (68%). The mean time in therapeutic range of the international normalised ratio (INR) 2.0-3.0 was 76.5%. The annual incidence of severe bleeding was 2.24% and of thromboembolism 2.65%. The incidence of intracranial bleeding was 0.37% per treatment year in the whole population, and 0.38% among patients with atrial fibrillation. In conclusion, warfarin treatment where patients spend a high proportion of time in the therapeutic range is safe and effective, and will continue to be a valid treatment option in the era of newer oral anticoagulants.

Note: The review process for this paper was fully handled by Christian Weber, Editor in Chief.

 
  • References

  • 1 De Caterina R, Husted S, Wallentin L. et al. Vitamin K antagonists in heart disease: current status and perspectives (Section III). Position paper of the ESC Working Group on Thrombosis--Task Force on Anticoagulants in Heart Disease. Thromb Haemost 2013; 110: 1087-1107.
  • 2 Sjalander A, Engstrom G, Berntorp E. et al. Risk of haemorrhagic stroke in patients with oral anticoagulation compared with the general population. J Intern Med 2003; 254: 434-438.
  • 3 Schulman S, Beyth RJ, Kearon C. et al. Hemorrhagic complications of anticoagulant and thrombolytic treatment: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133 (Suppl. 06) 257S-298S.
  • 4 Wallentin L, Yusuf S, Ezekowitz MD. et al. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet 2010; 376: 975-983.
  • 5 Wallentin L, Lopes RD, Hanna M. et al. Efficacy and safety of apixaban compared with warfarin at different levels of predicted international normalized ratio control for stroke prevention in atrial fibrillation. Circulation 2013; 127: 2166-2176.
  • 6 Gallego P, Roldan V, Marin F. et al. Cessation of oral anticoagulation in relation to mortality and the risk of thrombotic events in patients with atrial fibrillation. Thromb Haemost 2013; 110: 1189-1198.
  • 7 Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007; 146: 857-867.
  • 8 Wan Y, Heneghan C, Perera R. et al. Anticoagulation control and prediction of adverse events in patients with atrial fibrillation: a systematic review. Circulation Cardiovasc Qualit Outcom 2008; 01: 84-91.
  • 9 Gallagher AM, Setakis E, Plumb JM. et al. Risks of stroke and mortality associated with suboptimal anticoagulation in atrial fibrillation patients. Thromb Haemost 2011; 106: 968-977.
  • 10 Rosendaal FR, Cannegieter SC, van der Meer FJ. et al. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost 1993; 69: 236-239.
  • 11 Husted S, de Caterina R, Andreotti F. et al. Non-vitamin K antagonist oral anticoagulants (NOACs): No longer new or novel. Thromb Haemost 2014; 111: 781-782.
  • 12 Ruff CT, Giugliano RP, Braunwald E. et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014; 383: 955-962.
  • 13 Miller CS, Grandi SM, Shimony A. et al. Meta-analysis of efficacy and safety of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus warfarin in patients with atrial fibrillation. Am J Cardiol 2012; 110: 453-460.
  • 14 Connolly SJ, Ezekowitz MD, Yusuf S. et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139-1151.
  • 15 Patel MR, Mahaffey KW, Garg J. et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365: 883-891.
  • 16 Granger CB, Alexander JH, McMurray JJ. et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365: 981-992.
  • 17 Wieloch M, Själander A, Frykman V. et al. Anticoagulation control in Sweden: reports of time in therapeutic range, major bleeding, and thrombo-embolic complications from the national quality registry AuriculA. Eur Heart J 2011; 32: 2282-2289.
  • 18 Ericson L, Bergfeldt L, Björholt I. Atrial fibrillation: the cost of illness in Sweden. Eur J Health Econ 2011; 12: 479-487.
  • 19 Yearly Report Auricula. 2011
  • 20 Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 03: 692-694.
  • 21 Friberg L, Rosenqvist M, Lip GY. Net clinical benefit of warfarin in patients with atrial fibrillation: a report from the Swedish atrial fibrillation cohort study. Circulation 2012; 125: 2298-2307.
  • 22 Ludvigsson JF, Andersson E, Ekbom A. et al. External review and validation of the Swedish national inpatient register. BMC public Health 2011; 11: 450.