Key result
Standard-dose apixaban cuts stroke or systemic embolism ~41% vs. VKAs in advanced CKD.
Why the study?
The optimal apixaban dose for patients with AF and advanced CKD remains uncertain because randomized trials largely excluded this population and dose-specific evidence is limited.
Does standard- or reduced-dose apixaban improve stroke/systemic embolism and major bleeding in patients with atrial fibrillation and advanced chronic kidney disease compared to vitamin K antagonists?
Meta-Analysis (n=65,976)
Yes
Does standard- or reduced-dose apixaban improve stroke/systemic embolism and major bleeding in patients with atrial fibrillation and advanced chronic kidney disease compared to vitamin K antagonists?
Hazard Ratio: 0.59 (95% CI 0.39–0.89)
In patients with AF and advanced CKD (CrCl < 30 mL/min), both standard and reduced doses of apixaban offer superior efficacy and safety profiles compared to VKAs, with standard-dose apixaban possibly conferring an additional all-cause mortality benefit.
May support standard-dose apixaban over VKAs in AF with advanced CKD; extends excluded-population data but low-certainty evidence leaves practice change open.
Background: The optimal apixaban dose for patients with atrial fibrillation (AF) and advanced chronic kidney disease (CKD; CrCl < 30 mL/min) remains uncertain because randomized trials largely excluded this population, and dose-specific evidence is limited. Objectives: This study aimed to compare the efficacy and safety of standard- versus reduced-dose apixaban and to evaluate each regimen against vitamin K antagonists (VKAs). Methods: We conducted a systematic review (SR) and network meta-analysis (NMA) that complied with PRISMA 2020. PubMed, Scopus, ScienceDirect, Cochrane Library, and EBSCO Open Dissertations were searched through 10 January 2026. Randomized trials and cohort studies enrolling adults with AF and CrCl < 30 mL/min were included. Primary outcomes were stroke/systemic embolism (SE) and major bleeding; secondary outcomes were any bleeding and all-cause mortality. A frequentist random-effects NMA was conducted using a consistency model. Treatment effects were estimated as hazard ratios (HRs) with 95% confidence intervals (CIs). Pairwise meta-analyses were also performed for direct comparisons. Results: Nine studies involving 65,976 patients were included. In the NMA, standard-dose apixaban did not significantly differ from reduced-dose apixaban for stroke/SE, major bleeding, or any bleeding, but was associated with lower all-cause mortality (HR 0.73, 95% CI 0.62–0.87). Compared with VKAs, both standard- and reduced-dose apixaban were associated with lower risks of stroke/SE, major bleeding, any bleeding, and all-cause mortality. Conclusions: In AF patients with advanced CKD, both standard- and reduced-dose apixaban were associated with more favorable outcomes than VKAs, although the certainty of evidence was generally low.
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Sapapsap et al. (2026) conducted a meta-analysis in Atrial Fibrillation and Advanced Chronic Kidney Disease (CrCl < 30 mL/min) (n=65,976). Apixaban vs. Vitamin K antagonists (VKAs) was evaluated on Stroke or systemic embolism (SE) (HR 0.59, 95% CI 0.39-0.89). Standard-dose apixaban significantly reduced the risk of stroke or systemic embolism by 41% (HR 0.59) compared with vitamin K antagonists in patients with atrial fibrillation and advanced chronic kidney disease.
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