Skip to main content
Top
Published in: Clinical Research in Cardiology 12/2014

01-12-2014 | Original Paper

Adherence to warfarin treatment among patients with atrial fibrillation

Authors: Mika Skeppholm, Leif Friberg

Published in: Clinical Research in Cardiology | Issue 12/2014

Login to get access

Abstract

Background

Treatment with warfarin greatly reduces the risk of stroke related to atrial fibrillation, but will not be effective unless patients adhere to treatment. Lack of fixed dosing makes it difficult to objectively estimate adherence to treatment from prescription data.

Objective

To evaluate two methods that assess adherence to warfarin from prescription data.

Design

Retrospective study of Swedish health care registers.

Patients and methods

Age- and sex-specific dose requirements were determined from approx. 1 million blood tests and dosing instructions. By applying these dosages to 163,785 warfarin-treated patients with atrial fibrillation, we calculated the quantity of warfarin that was needed to keep these patients on effective treatment during a mean follow-up of 3.9 years and compared that with the dispensed quantities. The ratio of available drug/time at risk constitutes a measure of adherence on group level. In addition, time intervals between refills were used to assess discontinuation.

Results

Both methods showed that 45 % of the patients did not have enough warfarin to last 80 % of the time at risk. Between 16 and 21 % of the patients discontinued within the first year, followed by 8–9 % annually during the following years. Patients with high bleeding risk and patients with low embolic risk showed lower endurance.

Conclusions

Adherence to treatment with warfarin can be estimated on group level from prescription data and may be useful for comparison of adherence with warfarin and new oral anticoagulants. When applied to a large warfarin-treated cohort with atrial fibrillation, we found that adherence is low and that measures aiming for improvements are needed .
Appendix
Available only for authorised users
Literature
1.
go back to reference Camm AJ, Lip GY, De Caterina R et al (2012) 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. Europace 14:1385–1413PubMedCrossRef Camm AJ, Lip GY, De Caterina R et al (2012) 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. Europace 14:1385–1413PubMedCrossRef
2.
go back to reference Aguilar MI, Hart R (2005) Oral anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks. Cochrane Database Syst Rev 3:CD001927PubMed Aguilar MI, Hart R (2005) Oral anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks. Cochrane Database Syst Rev 3:CD001927PubMed
3.
go back to reference Rosendaal FR, Cannegieter SC, van der Meer FJ et al (1993) A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost 69:236–239PubMed Rosendaal FR, Cannegieter SC, van der Meer FJ et al (1993) A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost 69:236–239PubMed
4.
go back to reference Connolly SJ, Pogue J, Eikelboom J et al (2008) Benefit of oral anticoagulant over antiplatelet therapy in atrial fibrillation depends on the quality of international normalized ratio control achieved by centers and countries as measured by time in therapeutic range. Circulation 118:2029–2037PubMedCrossRef Connolly SJ, Pogue J, Eikelboom J et al (2008) Benefit of oral anticoagulant over antiplatelet therapy in atrial fibrillation depends on the quality of international normalized ratio control achieved by centers and countries as measured by time in therapeutic range. Circulation 118:2029–2037PubMedCrossRef
5.
go back to reference Morgan CL, McEwan P, Tukiendorf A et al (2009) Warfarin treatment in patients with atrial fibrillation: observing outcomes associated with varying levels of INR control. Thromb Res 124:37–41PubMedCrossRef Morgan CL, McEwan P, Tukiendorf A et al (2009) Warfarin treatment in patients with atrial fibrillation: observing outcomes associated with varying levels of INR control. Thromb Res 124:37–41PubMedCrossRef
6.
go back to reference Wallentin L, Yusuf S, Ezekowitz MD et al (2010) 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 376:975–983PubMedCrossRef Wallentin L, Yusuf S, Ezekowitz MD et al (2010) 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 376:975–983PubMedCrossRef
7.
go back to reference Patel MR, Mahaffey KW, Garg J et al (2011) Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. New Eng J Med 365:883–891PubMedCrossRef Patel MR, Mahaffey KW, Garg J et al (2011) Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. New Eng J Med 365:883–891PubMedCrossRef
8.
go back to reference Connolly SJ, Ezekowitz MD, Yusuf S et al (2009) Dabigatran versus warfarin in patients with atrial fibrillation. New Eng J Med 361:1139–1151PubMedCrossRef Connolly SJ, Ezekowitz MD, Yusuf S et al (2009) Dabigatran versus warfarin in patients with atrial fibrillation. New Eng J Med 361:1139–1151PubMedCrossRef
9.
go back to reference Granger CB, Alexander JH, McMurray JJ et al (2011) Apixaban versus warfarin in patients with atrial fibrillation. New Eng J Med 365:981–992PubMedCrossRef Granger CB, Alexander JH, McMurray JJ et al (2011) Apixaban versus warfarin in patients with atrial fibrillation. New Eng J Med 365:981–992PubMedCrossRef
10.
go back to reference Jorgensen AL, Hughes DA, Hanson A et al (2013) Adherence and variability in warfarin dose requirements: assessment in a prospective cohort. Pharmacogenomics 14:151–163PubMedCrossRef Jorgensen AL, Hughes DA, Hanson A et al (2013) Adherence and variability in warfarin dose requirements: assessment in a prospective cohort. Pharmacogenomics 14:151–163PubMedCrossRef
11.
go back to reference Sappok T, Faulstich A, Stuckert E et al (2001) Compliance with secondary prevention of ischemic stroke: a prospective evaluation. Stroke 32:1884–1889PubMedCrossRef Sappok T, Faulstich A, Stuckert E et al (2001) Compliance with secondary prevention of ischemic stroke: a prospective evaluation. Stroke 32:1884–1889PubMedCrossRef
12.
go back to reference Hamann GF, Weimar C, Glahn J et al (2003) Adherence to secondary stroke prevention strategies–results from the german stroke data bank. Cerebrovasc Dis 15:282–288PubMedCrossRef Hamann GF, Weimar C, Glahn J et al (2003) Adherence to secondary stroke prevention strategies–results from the german stroke data bank. Cerebrovasc Dis 15:282–288PubMedCrossRef
13.
go back to reference De Schryver EL, van Gijn J, Kappelle LJ et al (2005) Non-adherence to aspirin or oral anticoagulants in secondary prevention after ischaemic stroke. J Neurol 252:1316–1321PubMedCrossRef De Schryver EL, van Gijn J, Kappelle LJ et al (2005) Non-adherence to aspirin or oral anticoagulants in secondary prevention after ischaemic stroke. J Neurol 252:1316–1321PubMedCrossRef
14.
go back to reference Gomes T, Mamdani MM, Holbrook AM et al (2012) Persistence with therapy among patients treated with warfarin for atrial fibrillation. Arch Intern Med 172:1687–1689PubMedCrossRef Gomes T, Mamdani MM, Holbrook AM et al (2012) Persistence with therapy among patients treated with warfarin for atrial fibrillation. Arch Intern Med 172:1687–1689PubMedCrossRef
15.
go back to reference Maxwell W, Bennett CL (2012) Will newer anticoagulants improve therapy persistence? Arch Intern Med 172:1689–1690PubMedCrossRef Maxwell W, Bennett CL (2012) Will newer anticoagulants improve therapy persistence? Arch Intern Med 172:1689–1690PubMedCrossRef
16.
go back to reference Wang Y, Kong MC, Ko Y (2013) Comparison of three medication adherence measures in patients taking warfarin. J Thromb Thrombol 36:416–421CrossRef Wang Y, Kong MC, Ko Y (2013) Comparison of three medication adherence measures in patients taking warfarin. J Thromb Thrombol 36:416–421CrossRef
18.
go back to reference Mattson ME, Friedman LM (1984) Issues in medication adherence assessment in clinical trials of the national heart, lung, and blood institute. Controll Clin Trial 5:488–496CrossRef Mattson ME, Friedman LM (1984) Issues in medication adherence assessment in clinical trials of the national heart, lung, and blood institute. Controll Clin Trial 5:488–496CrossRef
19.
go back to reference Kimmel SE, Chen Z, Price M et al (2007) The influence of patient adherence on anticoagulation control with warfarin: results from the international normalized ratio adherence and genetics (in-range) study. Arch Intern Med 167:229–235PubMedCrossRef Kimmel SE, Chen Z, Price M et al (2007) The influence of patient adherence on anticoagulation control with warfarin: results from the international normalized ratio adherence and genetics (in-range) study. Arch Intern Med 167:229–235PubMedCrossRef
20.
go back to reference Yeaw J, Benner JS, Walt JG et al (2009) Comparing adherence and persistence across 6 chronic medication classes. J Manag Care Pharm 15:728–740PubMed Yeaw J, Benner JS, Walt JG et al (2009) Comparing adherence and persistence across 6 chronic medication classes. J Manag Care Pharm 15:728–740PubMed
21.
go back to reference Ewen S, Rettig-Ewen V, Mahfoud F et al (2014) Drug adherence in patients taking oral anticoagulation therapy. Clin Res Cardiol 103:173–182PubMedCrossRef Ewen S, Rettig-Ewen V, Mahfoud F et al (2014) Drug adherence in patients taking oral anticoagulation therapy. Clin Res Cardiol 103:173–182PubMedCrossRef
22.
go back to reference Hylek EM, Evans-Molina C, Shea C et al (2007) Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 115:2689–2696PubMedCrossRef Hylek EM, Evans-Molina C, Shea C et al (2007) Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 115:2689–2696PubMedCrossRef
23.
go back to reference Glader EL, Sjölander M, Eriksson M et al (2010) Persistent use of secondary preventive drugs declines rapidly during the first 2 years after stroke. Stroke 41:397–401PubMedCrossRef Glader EL, Sjölander M, Eriksson M et al (2010) Persistent use of secondary preventive drugs declines rapidly during the first 2 years after stroke. Stroke 41:397–401PubMedCrossRef
24.
go back to reference White HD, Gruber M, Feyzi J et al (2007) Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control: results from SPORTIF III and V. Arch Intern Med 167:239–245PubMedCrossRef White HD, Gruber M, Feyzi J et al (2007) Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control: results from SPORTIF III and V. Arch Intern Med 167:239–245PubMedCrossRef
25.
go back to reference Nieuwlaat R, Connolly BJ, Hubers LM, ACTIVE Investigators et al (2012) Quality of individual INR control and the risk of stroke and bleeding events in atrial fibrillation patients: a nested case control analysis of the ACTIVE W study. Thromb Res 129:715–719PubMedCrossRef Nieuwlaat R, Connolly BJ, Hubers LM, ACTIVE Investigators et al (2012) Quality of individual INR control and the risk of stroke and bleeding events in atrial fibrillation patients: a nested case control analysis of the ACTIVE W study. Thromb Res 129:715–719PubMedCrossRef
26.
go back to reference Casciano JP, Dotiwala ZJ, Martin BC et al (2013) The costs of warfarin underuse and nonadherence in patients with atrial fibrillation: a commercial insurer perspective. J Manag Care Pharm 19:302–316PubMed Casciano JP, Dotiwala ZJ, Martin BC et al (2013) The costs of warfarin underuse and nonadherence in patients with atrial fibrillation: a commercial insurer perspective. J Manag Care Pharm 19:302–316PubMed
Metadata
Title
Adherence to warfarin treatment among patients with atrial fibrillation
Authors
Mika Skeppholm
Leif Friberg
Publication date
01-12-2014
Publisher
Springer Berlin Heidelberg
Published in
Clinical Research in Cardiology / Issue 12/2014
Print ISSN: 1861-0684
Electronic ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-014-0742-y

Other articles of this Issue 12/2014

Clinical Research in Cardiology 12/2014 Go to the issue