Key result
Low-dose dabigatran did not significantly reduce the risk of ischemic stroke or systemic embolism compared to warfarin in patients with atrial fibrillation (HR 0.85).
Why the study?
Many AF patients receive DOAC doses lower than tested in clinical trials, creating a need to evaluate the comparative effectiveness and safety of low-dose DOACs versus warfarin or other DOACs.
Do low-dose DOACs reduce ischemic stroke or systemic embolism compared to warfarin or other DOACs in patients with atrial fibrillation?
Cohort (n=22,969)
Do low-dose DOACs reduce ischemic stroke or systemic embolism compared to warfarin or other DOACs in patients with atrial fibrillation?
Hazard Ratio: 0.85 (95% CI 0.51–1.4)
In older patients with atrial fibrillation, low-dose apixaban demonstrated a better safety profile than warfarin and other low-dose DOACs, while low-dose dabigatran showed a better effectiveness composite than warfarin but a worse safety profile than apixaban.
Low-dose dabigatran was associated with better effectiveness than warfarin in AF; leaves open whether findings extend to other low-dose DOACs or warrant practice change.
Aims: Observational studies of various dose levels of direct oral anticoagulants (DOACs) for patients with atrial fibrillation (AF) found that a high proportion of patients received a dose lower than the target dose tested in randomized controlled trials. There is a need to compare low-dose DOACs with warfarin or other DOACs on effectiveness and safety. Methods: Using administrative data from Quebec province, Canada, we built a cohort of new warfarin or DOAC users discharged from hospital between 2011 and 2017. We determined CHA 2 DS 2 -VASc and HAS-BLED scores, and comorbidities for 3-year prior cohort entry. The primary effectiveness endpoint was a composite of ischemic stroke/systemic embolism (SE), and secondary outcomes included a safety composite of major bleeding (MB) events and effectiveness composite (stroke/SE, death) at 1-year follow-up. We contrasted each low-dose DOAC with warfarin or other DOACs as references using inverse probability of treatment weighting to estimate marginal Cox hazard ratios (HRs). Results: The cohort comprised 22,969 patients (mean age: 80–86). We did not find a significant risk reduction for the stroke/SE primary effectiveness endpoint for DOACs vs. warfarin; however, we observed a significantly lower risk for low-dose dabigatran vs. warfarin (HR [95%CI]: 0.59 [0.42–0.81]) for effectiveness composite, mainly due to a lower death rate. The differences in effectiveness and safety composites between low-dose rivaroxaban vs. warfarin were not significant. However, low-dose apixaban had a better safety composite (HR: 0.68 [0.53–0.88]) vs. warfarin. Comparisons of dabigatran vs. apixaban showed a lower risk of stroke/SE (HR: 0.53 [0.30–0.93]) and a 2-fold higher risk of MB. The MB risk was higher for rivaroxaban than for apixaban (HR: 1.58 [1.09–2.29]). Conclusions: The results of this population-based study suggest that low-dose dabigatran has a better effective composite than warfarin. Compared with apixaban, low-dose dabigatran had a better effectiveness composite but a worse safety profile. Low-dose apixaban had a better safety composite than warfarin and other low-dose DOACs. Given that the comparative effectiveness and safety seem to vary from one DOAC to another, pharmacokinetic data for specific populations are now warranted.
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Perreault et al. (2022) conducted a cohort in Atrial Fibrillation (n=22,969). Low-dose dabigatran vs. Warfarin was evaluated on Composite of ischemic stroke or systemic embolism (SE) (HR 0.85, 95% CI 0.51-1.40). Low-dose dabigatran did not significantly reduce the risk of ischemic stroke or systemic embolism compared to warfarin in patients with atrial fibrillation (HR 0.85).
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