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Thromb Haemost. 2017 Dec;117(12):2291-2299. doi: 10.1160/TH17-03-0198. Epub 2017 Dec 6.

Renal Function, Time in Therapeutic Range and Outcomes in Warfarin-Treated Atrial Fibrillation Patients: A Retrospective Analysis of Nationwide Registries.

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Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark.
Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom.
Department of Nephrology, Copenhagen University Hospital Rigshospitalet, Righshospitalet, Denmark.
Institute of Health, Science and Technology, Aalborg University, Aalborg, Denmark.
The Danish Heart Foundation, Copenhagen, Denmark.
The National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark.


Patients with severely reduced renal function have been excluded from randomized controlled trials of oral anticoagulation in atrial fibrillation (AF). Warfarin treatment in this population is controversial and data on anticoagulation control and the impact on adverse outcomes are needed. By individual-level linkage of nationwide registries, we identified all patients discharged from hospitals with AF in Denmark between 1997 and 2011. Patients with available serum creatinine tests were categorized according to the estimated glomerular filtration rate (eGFR). Time in therapeutic range (TTR) was calculated using the Rosendaal method. The risk of stroke and bleeding was estimated using multivariable Cox regression analyses with eGFR and TTR estimated time dependently throughout follow-up. We identified 10,423 warfarin-treated AF patients with available international normalized ratio and creatinine tests; 5,527 with eGFR > 60 mL/min/1.73 m2, 4,524 with eGFR 30–60 mL/min/1.73 m2 and 372 with eGFR < 30 mL/min/1.73 m2. Median TTR was 66.7, 61.2 and 49.7% in patients with eGFR > 60, 30–59 and <30 mL/min/1.73 m2, respectively. A TTR < 70% was associated with a higher risk of stroke/thromboembolism (hazard ratio [HR]: 1.39; 95% confidence interval [CI]: 1.20–1.60) and bleeding (HR: 1.22; 95% CI: 1.05–1.42) among patients with eGFR of 30 to 59 and a trend towards higher risk of stroke/thromboembolism (HR: 1.24; 95% CI: 0.86–1.80) and bleeding (HR: 1.17; 95% CI: 0.83–1.65) among patients with eGFR < 30 mL/min/1.73 m2. In conclusion, warfarin-treated AF patients with reduced renal function have suboptimal anticoagulation control which was related to the risk of adverse outcomes.


Conflict of interest statement

Conflict of Interest: Dr. Bonde (none); Dr. Lip (Consultant for Bayer/Janssen, BMS/Pfizer, Biotronik, Medtronic, Boehringer Ingelheim, Microlife and Daiichi-Sankyo; Speaker for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim, Microlife, Roche and Daiichi-Sankyo, outside the submitted work); Kamper (personal fees from Boehringer Ingelheim outside the submitted work); Stærk (grants from Boehringer Ingelheim, outside the submitted work); Torp-Pedersen (grants and personal fees from Cardiome Merck, Sanofi, Daiichi, and grants from BMS, outside the submitted work); Gislason (grants from Bayer, Boehringer Ingelheim, Pfizer, AstraZeneca, Bristol-Myers Squibb, during the conduct of the study); Olesen (grants from the Capital Region of Denmark, Foundation for Health Research, during the conduct of the study; grants and other from Bristol-Myers Squibb, and other from Boehringer Ingelheim, outside the submitted work).

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