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Published on: February 28, 2012
Time-in-therapeutic-range defined warfarin and direct oral anticoagulants in atrial fibrillation: a Nationwide Cohort
Mika Lehto1,2, Alex Luojus2, Olli Halminen3
1Department of Internal Medicine, Jorvi Hospital, HUS Helsinki University Hospital, Helsinki, Finland.
Insights
Warfarin therapy for atrial fibrillation (AF) showed poorer outcomes with lower time-in-therapeutic-range (TTR). Higher TTR in warfarin users approached direct oral anticoagulant (DOAC) effectiveness and safety.
Area of Science:
- Cardiology
- Pharmacology
- Public Health
Background:
- Individual time-in-therapeutic-range (TTR) impact on warfarin effectiveness and safety in atrial fibrillation (AF) is not well understood compared to direct oral anticoagulants (DOACs).
- Understanding TTR's role is crucial for optimizing anticoagulation strategies in AF patients.
Purpose of the Study:
- To compare the effectiveness and safety of standard dose DOACs against warfarin in AF patients.
- To analyze warfarin effectiveness and safety based on patient-specific TTR quartiles.
Main Methods:
- Nationwide cohort study of new-onset AF patients in Finland (2011-2018).
- Cox regression with inverse probability of treatment weighting to assess risks of ischemic stroke (IS), intracranial hemorrhage (ICH), and mortality.
- Comparison of apixaban, dabigatran, rivaroxaban, and warfarin users.
Main Results:
- Median TTR for warfarin was 72%.
- Poorer TTR quartiles on warfarin showed significantly higher risks of IS and ICH compared to the reference quartile.
- The best TTR quartile on warfarin and rivaroxaban showed reduced IS and ICH risks.
- Mortality was lowest in the best TTR group.
Conclusions:
- Outcomes were unsatisfactory in the lowest TTR quartiles for warfarin users.
- High TTR warfarin groups demonstrated comparable effectiveness and safety to standard dose DOACs.
- Optimizing TTR is vital for warfarin therapy in AF.
Background:
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).
Objective:
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.
Materials And Methods:
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 (n = 12,426), dabigatran (n = 4545), rivaroxaban (n = 12,950) and warfarin (n = 43,548).
Results:
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.
Conclusions:
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.
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