Key result
Reduced-dose DOACs show similar ischemic stroke risk compared to well-managed warfarin.
Why the study?
Reduced dose DOACs are the first choice for stroke prevention in AF patients with high bleeding risk or renal insufficiency, but their outcomes compared with warfarin needed evaluation.
Do reduced dose DOACs prevent ischemic stroke as effectively and safely as warfarin in patients with new-onset atrial fibrillation?
Cohort (n=52,384)
Yes
Do reduced dose DOACs prevent ischemic stroke as effectively and safely as warfarin in patients with new-onset atrial fibrillation?
Effect estimate: Apixaban HR 0.76, Rivaroxaban HR 1.00, Dabigatran HR 1.08 (vs 3rd TTR warfarin quartile)
Reduced dose DOACs offer safe and efficient stroke prevention similar to well-controlled warfarin, though warfarin with excellent long-term control maintains the lowest risk of adverse events.
Reduced-dose DOACs may support stroke prevention comparable to good-TTR warfarin in new-onset AF; leaves open whether excellent TTR warfarin yields lowest bleeding and mortality.
Aims: Direct oral anticoagulants (DOACs) at reduced dosage regimens are the first choice of ischaemic stroke (IS) prevention for patients with atrial fibrillation (AF) and elevated bleeding risk or renal insufficiency. We compared the outcomes of reduced dose DOACs and warfarin. Methods and results: = 43 548). Patients on warfarin were grouped into quartiles by their individual time-in-therapeutic range (TTR), with the second best TTR quartile as a reference group for comparisons. Risk of IS was highest in the low TTR quartiles of warfarin, lowest in the best TTR quartile (0.65 95% confidence interval, 0.51-0.83), and did not differ for dabigatran, rivaroxaban, and apixaban compared with the second best TTR quartile. Risk of ICH was highest in low TTR quartiles of warfarin (HRs 7.20, 5.48-9.46 and 1.91, 1.44-2.55), and was not different in patients on dabigatran, rivaroxaban, and apixaban. Risk of all-cause death and bleeding were lowest in the two best TTR quartiles, and highest in the poorest TTR group. Mortality was higher for dabigatran, rivaroxaban, and apixaban, compared with the second best TTR quartile of warfarin. Conclusion: DOACs with reduced doses are efficient and safe stroke prevention therapy in high-risk patients with AF when compared with warfarin therapy of sufficient TTR. In this comparison, warfarin therapy of excellent TTR-quality was associated with the lowest risk of bleeding and mortality.
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Luojus et al. (2025) conducted a cohort in New-onset non-valvular atrial fibrillation (n=52,384). Reduced dose direct oral anticoagulants (dabigatran, rivaroxaban, apixaban) vs. Warfarin (categorized by time-in-therapeutic range quartiles) was evaluated on Ischemic stroke (Apixaban HR 0.76, Rivaroxaban HR 1.00, Dabigatran HR 1.08 (vs 3rd TTR warfarin quartile)). Reduced dose DOACs resulted in a similar risk of ischemic stroke compared with warfarin therapy of good time-in-therapeutic range, though excellent TTR warfarin was associated with the lowest overall risk of bleeding and mortality.
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