Selection, management, and outcome of vitamin K antagonist-treated patients with atrial fibrillation not switched to novel oral anticoagulants

Franziska Michalski; Luise Tittl; Sebastian Werth; Ulrike Hänsel; Sven Pannach; Kurtulus Sahin; Norbert Weiss; Jan Beyer-Westendorf

doi:10.1160/TH15-02-0116

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2015; 114(05): 1076-1084
DOI: 10.1160/TH15-02-0116

Stroke, Systemic or Venous Thromboembolism

Schattauer GmbH

Selection, management, and outcome of vitamin K antagonist-treated patients with atrial fibrillation not switched to novel oral anticoagulants

Results from the Dresden NOAC registry

Authors

Franziska Michalski

¹Center for Vascular Medicine and Department of Medicine III, Division of Angiology, University Hospital “Carl Gustav Carus”, Technische Universität Dresden, Dresden, Germany
Luise Tittl

¹Center for Vascular Medicine and Department of Medicine III, Division of Angiology, University Hospital “Carl Gustav Carus”, Technische Universität Dresden, Dresden, Germany
Sebastian Werth

¹Center for Vascular Medicine and Department of Medicine III, Division of Angiology, University Hospital “Carl Gustav Carus”, Technische Universität Dresden, Dresden, Germany
Ulrike Hänsel

¹Center for Vascular Medicine and Department of Medicine III, Division of Angiology, University Hospital “Carl Gustav Carus”, Technische Universität Dresden, Dresden, Germany
Sven Pannach

²Division Gastroenterology, Department of Medicine I, University Hospital “Carl Gustav Carus” Dresden, Dresden, Germany
Kurtulus Sahin

³ClinStat GmbH, Institute for Clinical Research and Statistics, Cologne, Germany
Norbert Weiss

¹Center for Vascular Medicine and Department of Medicine III, Division of Angiology, University Hospital “Carl Gustav Carus”, Technische Universität Dresden, Dresden, Germany
Jan Beyer-Westendorf

¹Center for Vascular Medicine and Department of Medicine III, Division of Angiology, University Hospital “Carl Gustav Carus”, Technische Universität Dresden, Dresden, Germany

Abstract

Summary

Atrial fibrillation (AF) patients treated with well-controlled vitamin K antagonists (VKAs) may benefit less from non-vitamin K antagonist oral anticoagulants (NOACs) because they are supposed to be at low risk of thromboembolic and bleeding complications. However, little is known about the selection, management, and outcome of such “stable” VKA patients in current practice. We assessed characteristics, VKA persistence and 12 months' outcome of AF patients selected for VKA continuation. On March 1, 2013, the Dresden NOAC registry opened recruitment of patients continuing on VKA for sites that had been actively recruiting AF patients treated with NOACs in the prior 18 months. Patient characteristics were compared with those of NOAC patients from the same sites. Four hundred twenty-seven VKA patients had a significantly lower bleeding risk profile compared with 706 patients selected for NOAC treatment. For VKA, international normalised ratio time-in-therapeutic range before enrolment was 71% and increased to 75% during a mean follow-up of 15 months. Rates of stroke/transient ischaemic attack/systemic embolism were 1.3/100 patient-years (intention-to-treat) and 0.94/100 patient-years (as-treated). On-treatment rate of ISTH major bleeding was 4.15/100 patient-years (95% CI 2.60–6.29) with a case-fatality rate of 16.3% (all-cause mortality at day 90 after major bleeding). In conclusion, in daily care, AF patients selected for VKA therapy are healthier than those treated with NOAC, demonstrate a high quality of anticoagulant control and very low stroke rates. However, despite adequate patient selection and INR control, the risk of major VKA bleeding is unacceptably high and bleeding outcome is poor.

Keywords

Anticoagulants - atrial fibrillation - bleeding - outcome - vitamin K antagonists

Full Text

References

References
1 van Walraven C, Jennings A, Oake N. et al. Effect of study setting on anticoagulation control: a systematic review and metaregression. Chest 2006; 129: 1155-1166.
2 Beyth RJ, Quinn LM, Landefeld CS. Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin. Am J Med 1998; 105: 91-99.
3 Gitter MJ, Jaeger TM, Petterson TM. et al. Bleeding and thromboembolism during anticoagulant therapy: a population-based study in Rochester, Minnesota. Mayo Clin Proc 1995; 70: 725-733.
4 Steffensen FH, Kristensen K, Ejlersen E. et al. Major haemorrhagic complications during oral anticoagulant therapy in a Danish population-based cohort. J Intern Med 1997; 242: 497-503.
5 Willey VJ, Bullano MF, Hauch O. et al. Management patterns and outcomes of patients with venous thromboembolism in the usual community practice setting. Clin Ther 2004; 26: 1149-1159.
6 Gomes T, Mamdani MM, Holbrook AM. et al. Rates of hemorrhage during warfarin therapy for atrial fibrillation. Cmaj 2013; 185: E121-127.
7 Linkins LA, Choi PT, Douketis JD. Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. Ann Intern Med 2003; 139: 893-900.
8 Halbritter K, Beyer-Westendorf J, Nowotny J. et al. Hospitalization for Vitamin-K-Antagonist-related bleeding – treatment patterns and outcome. J Thromb Haemost 2013; 11: 651-659.
9 Patel MR, Mahaffey KW, Garg J. et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365: 883-891.
10 Bauersachs R, Berkowitz SD, Brenner B. et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363: 2499-2510.
11 Buller HR, Prins MH, Lensin AW. et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012; 366: 1287-1297.
12 Prins MH, Lensing AW, Bauersachs R. et al. Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies. Thromb J 2013; 11: 21.
13 Stollberger C, Finsterer J. Contra: “New oral anticoagulants should not be used as 1st choice for secondary stroke prevention in atrial fibrillation”. Thromb Haemost 2013; 110: 496-500.
14 Beyer-Westendorf J, Gelbricht V, Forster K. et al. Safety of switching from Vitamin-K antagonists to dabigatran or rivaroxaban in daily care – results from the Dresden NOAC registry. Br J Clin Pharmacol. 2014 in press.
15 Beyer-Westendorf J, Gelbricht V, Forster K. et al. Peri-interventional management of novel oral anticoagulants in daily care: results from the prospective Dresden NOAC registry. Eur Heart J 2014; 35: 1888-1896.
16 Beyer-Westendorf J, Forster K, Pannach S. et al. Rates, management, and outcome of rivaroxaban bleeding in daily care: results from the Dresden NOAC registry. Blood 2014; 124: 955-962.
17 Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3: 692-694.
18 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.
19 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.
20 Piccini JP, Hellkamp AS, Lokhnygina Y. et al. Relationship between time in therapeutic range and comparative treatment effect of rivaroxaban and warfarin: results from the ROCKET AF trial. J Am Heart Assoc 2014; 3: e000521.
21 Beyer-Westendorf J, Ebertz F, Forster K. et al. Effectiveness and safety of dabigatran therapy in daily-care patients with atrial fibrillation. Results from the Dresden NOAC Registry. Thromb Haemost 2015; 113: 1247-1257.
22 Amin A, Deitelzweig S, Jing Y. et al. Estimation of the impact of warfarin's time-in-therapeutic range on stroke and major bleeding rates and its influence on the medical cost avoidance associated with novel oral anticoagulant use-learnings from ARISTOTLE, ROCKET-AF, and RE-LY trials. J Thromb Thrombolysis 2014; 38: 150-159.
23 Graham DJ, Reichman ME, Wernecke M. et al. Cardiovascular, Bleeding, and Mortality Risks in Elderly Medicare Patients Treated with Dabigatran or Warfarin for Non-Valvular Atrial Fibrillation. Circulation. 2014 Epub ahead of print.
24 Camm AJ, Lip GY, De Caterina R. et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 2012; 33: 2719-2747.
25 Gallagher AM, Rietbrock S, Plumb J. et al. Initiation and persistence of warfarin or aspirin in patients with chronic atrial fibrillation in general practice: do the appropriate patients receive stroke prophylaxis?. J Thromb Haemost 2008; 6: 1500-1506.
26 Fang MC, Go AS, Chang Y. et al. Death and disability from warfarin-associated intracranial and extracranial hemorrhages. Am J Med 2007; 120: 700-705.
27 Gomes T, Mamdani MM, Holbrook AM. et al. Persistence with therapy among patients treated with warfarin for atrial fibrillation. Arch Intern Med 2012; 172: 1687-1689.
28 Hylek EM, Evans-Molina C, Shea C. et al. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007; 115: 2689-2696.