Key result
In patients with non-valvular atrial fibrillation on oral anticoagulants, moderately impaired renal function (CrCl 30 to <50 mL/min) was associated with a significantly increased risk of ischemic events (HR 1.70) compared to preserved renal function.
Why the study?
Renal function influences oral anticoagulant pharmacokinetics in AF, but its differential impact across specific agents remains unclear.
Do different oral anticoagulants prevent ischemic events without excessive bleeding in patients with non-valvular atrial fibrillation across varying levels of renal function?
Cohort (n=7,239)
Yes
Do different oral anticoagulants prevent ischemic events without excessive bleeding in patients with non-valvular atrial fibrillation across varying levels of renal function?
In patients with atrial fibrillation on oral anticoagulants, worsening renal function increases the risk of both ischemic and bleeding events, though apixaban uniquely demonstrated no significant risk increase across declining creatinine clearance levels.
Answers are grounded in this paper and cite their sources.
Moderately impaired renal function signals higher ischemic risk on OACs in AF; hypothesis-generating for differential effects by CrCl and leaves optimal agent open.
BACKGROUND: Renal function influences the pharmacokinetics of oral anticoagulants in atrial fibrillation (AF), potentially affecting both efficacy and bleeding risk. However, its differential impact across specific agents remains unclear. In this study, we aimed to evaluate the association between renal function and ischemic and bleeding risks in patients with AF, with analyses stratified by anticoagulant type. METHODS: We analyzed 7239 patients with non-valvular AF from the DIRECT-Extend registry, a pooled dataset of three large-scale registries. Creatinine clearance (CrCl) was calculated using the Cockcroft-Gault formula and categorized into ≥50, 30 to <50, and 15 to <30 mL/min. The primary ischemic endpoint was stroke or systemic embolism, and the primary bleeding endpoint was major bleeding. Cox proportional hazard models and restricted cubic spline analyses assessed associations between CrCl and outcomes, with subgroup analyses by anticoagulant type. RESULTS: Lower CrCl was associated with older age, female sex, and greater comorbidity burden. Impaired renal function was significantly associated with higher ischemic and bleeding risks. Spline analysis demonstrated a continuous increase in both risks with declining CrCl, with a nonlinear relationship for bleeding. Subgroup analyses revealed significant associations between reduced CrCl and ischemic risk in patients on dabigatran, rivaroxaban, edoxaban, and warfarin. Increased bleeding risk was evident for edoxaban and warfarin at lower CrCl levels. No significant association was observed between CrCl and either endpoint in patients receiving apixaban. CONCLUSION: In this large real-world cohort, declining renal function was associated with increased ischemic and bleeding risks, highlighting the importance of renal function-based risk assessment in the management of anticoagulation therapy.
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Matsuoka et al. (2025) conducted a cohort in Non-valvular atrial fibrillation (n=7,239). Impaired renal function (CrCl 30 to <50 mL/min) vs. Preserved renal function (CrCl ≥50 mL/min) was evaluated on Primary ischemic endpoint (composite of any stroke and systemic embolism) (HR 1.70, 95% CI 1.32-2.19, p=<0.001). In patients with non-valvular atrial fibrillation on oral anticoagulants, moderately impaired renal function (CrCl 30 to <50 mL/min) was associated with a significantly increased risk of ischemic events (HR 1.70) compared to preserved renal function.
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