Time-in-therapeutic-range defined warfarin and direct oral anticoagulants in atrial fibrillation: a Nationwide Cohort Study

• Published in: Annals of medicine (Helsinki) Vol. 56; no. 1; p. 2364825
• Main Authors: Lehto, Mika, Luojus, Alex, Halminen, Olli, Haukka, Jari, Putaala, Jukka, Linna, Miika, Mustonen, Pirjo, Kinnunen, Janne, Lehtonen, Ossi, Teppo, Konsta, Tiili, Paula, Kouki, Elis, Itäinen-Strömberg, Saga, Niemi, Mikko, Aro, Aapo L, Hartikainen, Juha, Airaksinen, K E Juhani
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01-12-2024; Taylor & Francis Group
• Subjects: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants - administration & dosage; Anticoagulants - adverse effects; Atrial fibrillation; Atrial Fibrillation - complications; Atrial Fibrillation - drug therapy; Cardiology & Cardiovascular Disorders; Cohort Studies; Dabigatran - administration & dosage; Dabigatran - adverse effects; direct oral anticoagulant; Female; Finland - epidemiology; Humans; International Normalized Ratio; Intracranial Hemorrhages - chemically induced; Intracranial Hemorrhages - epidemiology; Ischemic Stroke - epidemiology; Ischemic Stroke - etiology; Ischemic Stroke - prevention & control; Male; Middle Aged; oral anticoagulation; Pyrazoles - administration & dosage; Pyrazoles - adverse effects; Pyridones - administration & dosage; Pyridones - adverse effects; Pyridones - therapeutic use; real world data; Rivaroxaban - administration & dosage; Rivaroxaban - adverse effects; stroke; Stroke - epidemiology; Stroke - etiology; Stroke - prevention & control; Treatment Outcome; warfarin; Warfarin - administration & dosage; Warfarin - adverse effects; Finland; real world data; oral anticoagulation; stroke; Atrial fibrillation; direct oral anticoagulant; warfarin
• ISSN: 0785-3890; 1365-2060
• DOI: 10.1080/07853890.2024.2364825

Little is known how individual time-in-therapeutic-range (TTR) impacts the effectiveness and safety of warfarin therapy compared to direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF).
To compare the effectiveness and safety of standard dose DOACs to warfarin in patients with AF, while categorizing warfarin treated patients into quartiles based on their individual TTR.
We conducted a nationwide study including all patients with new-onset AF between 2011 and 2018 in Finland. Hazard ratios (HR) were calculated using Cox regression analysis with the inverse probability of treatment weighted method to assess the risks of ischaemic stroke (IS), intracranial haemorrhage (ICH) and mortality for users of apixaban (
 = 12,426), dabigatran (
 = 4545), rivaroxaban (
 = 12,950) and warfarin (
 = 43,548).
The median TTR for warfarin users was 72%. Compared to the second best TTR quartile (reference), the risk of IS was higher in the two poorest TTR quartiles, and lower in the best TTR quartile and on rivaroxaban [2.35 (95% confidence interval, 1.85-2.85), 1.44 (1.18-1.75), 0.60 (0.47-0.77) and 0.72 (0.56-0.92)]. These differences were non-significant for apixaban and dabigatran. HR of ICH was 6.38 (4.88-8.35) and 1.87 (1.41-2.49) in the two poorest TTR groups, 1.44 (1.02-1.93) on rivaroxaban, and 0.58 (0.40-0.85) in the best TTR group compared to the reference group. Mortality was higher in the two poorest TTR groups and lowest in the best TTR group.
The outcome was unsatisfactory in the two lowest TTR quartiles - in half of the patients treated with warfarin. The differences between the high TTR groups and standard dose DOACs were absent or modest.