Efficacy and Safety of Apixaban Compared With Warfarin at Different Levels of Predicted International Normalized Ratio Control for Stroke Prevention in Atrial Fibrillation
Why the study?
Does apixaban reduce stroke or systemic embolism, major bleeding, and mortality compared to warfarin across different levels of predicted INR control in patients with atrial fibrillation?
Population
18,201 patients with atrial fibrillation
Comparison
Apixaban 5 mg twice daily for at least 12 months vs Warfarin for at least 12 months
Design
RCT, randomized
Follow-up
at least 12 months
Authors
Discussion
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Implication
Apixaban benefits persist across TTR levels; reinforces consistent advantages over warfarin in AF irrespective of center INR control.
Key Points
- To evaluate the efficacy and safety of apixaban compared with warfarin across different predicted levels of international normalized ratio (INR) time in therapeutic range (TTR) in patients with atrial fibrillation.
- Secondary analysis of the ARISTOTLE randomized trial evaluating 18,201 patients with atrial fibrillation assigned to apixaban (5 mg twice daily) or warfarin for at least 12 months.
- Predicted center-average TTR and individual-patient TTR using linear mixed models incorporating clinical characteristics, center random effects, and country fixed effects.
- Median center average TTR was 66% (interquartile range, 61% to 71%).
- Apixaban reduced stroke or systemic embolism across lowest and highest center average TTR quartiles (HR 0.73, 95% CI 0.53–1.00 vs HR 0.88, 95% CI 0.57–1.35; Pinteraction = 0.078) and showed identical mortality reductions across both quartiles (HR 0.91, 95% CI 0.74–1.13 vs HR 0.91, 95% CI 0.71–1.16; Pinteraction = 0.34).
- Major bleeding was lower with apixaban across lowest and highest center average TTR quartiles (HR 0.50, 95% CI 0.36–0.70 vs HR 0.75, 95% CI 0.58–0.97; Pinteraction = 0.095), with consistent patterns observed across individual TTR quartiles.
Structured PICO
Does apixaban reduce stroke or systemic embolism, major bleeding, and mortality compared to warfarin across different levels of predicted INR control in patients with atrial fibrillation?
P
Population
18,201 patients with atrial fibrillation
I
Intervention
Apixaban 5 mg twice daily for at least 12 months
C
Comparator
Warfarin for at least 12 months
O
Outcome
Stroke or systemic embolismhard clinical
Apixaban provides consistent benefits over warfarin for stroke prevention, bleeding reduction, and mortality in atrial fibrillation, regardless of the predicted quality of INR control at the center or patient level.
Cite This Study
Wallentin et al. (2013) studied this question.