What is the clinical evidence from this study?

Study design: Cohort. Population: atrial fibrillation (n=14865). Intervention: Inappropriate NOAC dosing (potential overdosing or underdosing) vs. Appropriate NOAC dosing. Primary outcome: major bleeding (HR 2.19, 95% CI 1.07 to 4.46).

What question did this study set out to answer?

This study aims to analyze the dosing patterns of non-vitamin K antagonist oral anticoagulants and their related outcomes in patients with atrial fibrillation and renal dysfunction.

June 30, 2026

Non–Vitamin K Antagonist Oral Anticoagulant Dosing in Patients With Atrial Fibrillation and Renal Dysfunction

Key Result

Potential overdosing of NOACs in patients with a renal indication was associated with a higher risk of major bleeding (HR 2.19; 95% CI 1.07-4.46), while underdosing apixaban increased stroke risk.

Key Points

This study aims to analyze the dosing patterns of non-vitamin K antagonist oral anticoagulants and their related outcomes in patients with atrial fibrillation and renal dysfunction.
Analyzed a large U.S. database of 14,865 patients with atrial fibrillation
Examined dosing patterns of apixaban, dabigatran, and rivaroxaban regarding renal indications
Utilized Cox proportional hazards regression on propensity score-matched cohorts for outcome investigation.
43.0% of patients with a renal indication for dose reduction were potentially overdosed, leading to increased major bleeding risk (HR: 2.19; 95% CI: 1.07-4.46)
13.3% of patients without renal indication were underdosed, resulting in higher stroke risk (HR: 4.87; 95% CI: 1.30-18.26)
No significant bleeding differences in underdosed apixaban-treated patients without renal indication observed.

Study Design

Type

Cohort (n=14,865)

Multicenter

Yes

Structured PICO

Does off-label NOAC dosing based on renal function increase the risk of stroke or major bleeding in patients with atrial fibrillation?

Population

14,865 patients with atrial fibrillation initiating apixaban, dabigatran, or rivaroxaban identified from a large U.S. administrative database.

Exposure

Off-label NOAC dosing (standard dose when renal indication for reduction is present [potential overdosing], or reduced dose when no renal indication is present [potential underdosing])

Comparator

On-label NOAC dosing (reduced dose when renal indication is present, or standard dose when no renal indication is present)

Outcome

Stroke (ischemic stroke and systemic embolism) and major bleedinghard clinical

In routine clinical practice, inappropriate NOAC dosing based on renal function is common and associated with increased risks of major bleeding (when overdosed) and stroke (when underdosed with apixaban).

Main Result

Hazard Ratio: 2.19 (95% CI 1.07–4.46)

Abstract

BACKGROUND: Dose reduction of non-vitamin K antagonist oral anticoagulants (NOACs) is indicated in patients with atrial fibrillation (AF) with renal impairment. Failure to reduce the dose in patients with severe kidney disease may increase bleeding risk, whereas dose reductions without a firm indication may decrease the effectiveness of stroke prevention. OBJECTIVES: The goal of this study was to investigate NOAC dosing patterns and associated outcomes, i.e., stroke (ischemic stroke and systemic embolism) and major bleeding in patients treated in routine clinical practice. METHODS: Using a large U.S. administrative database, 14,865 patients with AF were identified who initiated apixaban, dabigatran, or rivaroxaban between October 1, 2010, and September 30, 2015. We examined use of a standard dose in patients with a renal indication for dose reduction (potential overdosing) and use of a reduced dose when the renal indication is not present (potential underdosing). Cox proportional hazards regression was performed in propensity score-matched cohorts to investigate the outcomes. RESULTS: Among the 1,473 patients with a renal indication for dose reduction, 43.0% were potentially overdosed, which was associated with a higher risk of major bleeding (hazard ratio: 2.19; 95% confidence interval: 1.07 to 4.46) but no statistically significant difference in stroke (3 NOACs pooled). Among the 13,392 patients with no renal indication for dose reduction, 13.3% were potentially underdosed. This underdosing was associated with a higher risk of stroke (hazard ratio: 4.87; 95% confidence interval: 1.30 to 18.26) but no statistically significant difference in major bleeding in apixaban-treated patients. There were no statistically significant relationships in dabigatran- or rivaroxaban-treated patients without a renal indication. CONCLUSIONS: In routine clinical practice, prescribed NOAC doses are often inconsistent with drug labeling. These prescribing patterns may be associated with worse safety with no benefit in effectiveness in patients with severe kidney disease and worse effectiveness with no benefit in safety in apixaban-treated patients with normal or mildly impaired renal function.

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