Author + information
- Received February 22, 2018
- Revision received June 24, 2018
- Accepted June 25, 2018
- Published online September 10, 2018.
- Anders Nissen Bonde, MDa,∗ (, )@uni_copenhagen@unibirmingham,
- Laila Staerk, MDa,
- Christina J-Y. Lee, MDa,b,
- Naja Emborg Vinding, MBc,
- Casper N. Bang, MD, PhDd,e,
- Christian Torp-Pedersen, MD, DMSca,b,
- Gunnar Gislason, MD, PhDa,e,
- Gregory Y.H. Lip, MDf,g,∗ and
- Jonas Bjerring Olesen, MD, PhDa,∗
- aCopenhagen University Hospital Herlev and Gentofte, Hellerup, Denmark
- bDepartment of Health Science and Technology, Aalborg University, Aalborg University Hospital, Aalborg, Denmark
- cCopenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- dDepartment of Cardiology, Zealand University Hospital Roskilde, Roskilde, Denmark
- eDepartment of Cardiovascular Epidemiology and Research, The Danish Heart Foundation, Copenhagen, Denmark
- fInstitute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom
- gAalborg Thrombosis Research Unit, Aalborg University, Aalborg, Denmark
- ↵∗Address for correspondence:
Dr. Anders Nissen Bonde, Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Post 635, Kildegaardsvej 28, 2900 Hellerup, Denmark.
Background Atrial fibrillation (AF) patients on a vitamin K antagonist (VKA) with time in therapeutic range (TTR) ≥70% are not recommended to switch to a direct oral anticoagulant according to guidelines.
Objectives This study sought to assess future TTR and risk of stroke/thromboembolism and major bleeding among AF patients on VKA with TTR ≥70%.
Methods The authors used Danish nationwide registries to identify AF patients on VKA from 1997 to 2011 with available international normalized ratio values. Patients were included 6 months after VKA initiation, divided according to TTR, and followed for 12 months after inclusion. Cox proportional hazard models estimated hazard ratios (HRs). TTR was examined both as a baseline variable and as a time-dependent covariate in the Cox models.
Results Of the 4,772 included AF patients still on VKA 6 months after initiation, 1,691 (35.4%) had a TTR ≥70%, and 3,081 (65.6%) had a TTR <70%. Among patients with prior TTR ≥70% still on treatment 12 months after inclusion, only 513 (55.7%) still had a TTR ≥70%. Compared with prior TTR ≥70%, prior TTR <70% was not associated with a higher risk of stroke/thromboembolism (HR: 1.14; 95% confidence interval [CI]: 0.77 to 1.70) or major bleeding (HR: 1.12; 95% CI: 0.84 to 1.49). When the authors estimated TTR time-dependently during follow-up, TTR <70% was associated with an increased risk of stroke/thromboembolism (HR: 1.91; 95% CI: 1.30 to 2.82) and major bleeding (HR: 1.34; 95% CI: 1.02 to 1.76).
Conclusions Among AF patients on VKA, almost one-half of patients with prior TTR ≥70% had TTR <70% during the following year. Prior TTR ≥70% per se had limited long-term prognostic value.
- atrial fibrillation
- international normalized ratio
- time in therapeutic range
- vitamin K antagonist
↵∗ Drs. Lip and Olesen contributed equally to this work and are joint senior authors.
This study was funded by an unrestricted grant from the Capital Region of Denmark, Foundation for Health Research. Dr. Staerk has received funding for research from Boehringer Ingelheim. Dr. Bang has received funding for research from the Danish Heart Foundation, Maersk, and Spies. Dr. Torp-Pedersen has received research grants from Bayer and Biotronic; and speaker fees from Bayer. Prof. Gislason has received research grants from Bristol-Myers Squibb, Pfizer, Boehringer Ingelheim, Bayer, and AstraZeneca. Dr. Lip has been a consultant for Bayer/Janssen, Bristol-Myers Squibb/Pfizer, Biotronik, Medtronic, Boehringer Ingelheim, Novartis, Verseon, and Daiichi-Sankyo; and has received speaker fees from Bayer, Bristol-Myers Squibb/Pfizer, Medtronic, Boehringer Ingelheim, and Daiichi-Sankyo. Dr. Olesen has received speaker fees from Bristol-Myers Squibb, Boehringer Ingelheim, Bayer, and AstraZeneca; has received research funding the Lundbeck Foundation, Bristol-Myers Squibb, and the Capital Region of Denmark, Foundation for Health Research; has been a consultant for Bristol-Myers Squibb, Boehringer Ingelheim, and Novo Nordisk; and has been an advisory board member for Novo Nordisk. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received February 22, 2018.
- Revision received June 24, 2018.
- Accepted June 25, 2018.
- 2018 American College of Cardiology Foundation
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