Comparison of Acute Kidney Injury Risks Between Direct Oral Anticoagulants in Nonvalvular Atrial Fibrillation: A Propensity Score-weighted Retrospective Observational Cohort Study

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Nonvalvular atrial fibrillation (n=492). Intervention: Apixaban or Rivaroxaban vs. Edoxaban (reference). Primary outcome: Cumulative incidence of acute kidney injury (AKI) within 1 year of treatment initiation (defined as serum creatinine increase >=1.5-fold from baseline) (HR 2.12 (apixaban vs edoxaban); HR 2.92 (rivaroxaban vs edoxaban), 95% CI 1.12-4.02, p=0.021).

Q: What does this research mean for the field?

In patients with nonvalvular atrial fibrillation, edoxaban is associated with a significantly lower one-year incidence and risk of acute kidney injury compared to apixaban and rivaroxaban. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Tomohiro Aigami; Tomoyuki Ishigo; Yuta Ibe; Satoshi Fujii; Masahide Fukudo; Takaki Toda

doi:10.21203/rs.3.rs-10901432/v1

October 6, 2026Open Access

Comparison of Acute Kidney Injury Risks Between Direct Oral Anticoagulants in Nonvalvular Atrial Fibrillation: A Propensity Score-weighted Retrospective Observational Cohort Study

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Why the study?

Anticoagulant use can cause anticoagulant-related nephropathy characterized by acute kidney injury, and the incidence and severity of AKI associated with direct oral anticoagulants in nonvalvular atrial fibrillation remained unclear.

Does edoxaban reduce the cumulative incidence of acute kidney injury within 1 year compared with apixaban and rivaroxaban in patients with nonvalvular atrial fibrillation?

Key Points

To compare the incidence of acute kidney injury among patients with nonvalvular atrial fibrillation treated with different direct oral anticoagulants.
Single-center, retrospective observational cohort study of 492 patients with nonvalvular atrial fibrillation who initiated edoxaban (N=307), apixaban (N=112), or rivaroxaban (N=73) between January 2015 and December 2023.
Primary outcome was the cumulative incidence of acute kidney injury within the first year of treatment.
Inverse probability of treatment weighting (IPTW) was applied to adjust for baseline confounders, followed by multivariable outcome regression in a weighted Cox proportional hazards model.
The cumulative incidence of acute kidney injury within 1 year was 10.8% for edoxaban, 23.3% for apixaban, and 25.0% for rivaroxaban (IPTW-adjusted p < 0.001).
In multivariable Cox regression with IPTW adjustment, apixaban (adjusted HR, 2.12; 95% CI, 1.12–4.02; p = 0.021) and rivaroxaban (adjusted HR, 2.92; 95% CI, 1.44–5.92; p = 0.003) demonstrated significantly higher risks of acute kidney injury compared with edoxaban.
In patients with baseline eGFR < 60 mL/min/1.73 m2, rivaroxaban was significantly associated with acute kidney injury compared with edoxaban (adjusted HR, 5.92; 95% CI, 1.82–19.2; p = 0.003), whereas apixaban was not (adjusted HR, 2.59; 95% CI, 0.72–9.36; p = 0.145).

Study Design

Type

Cohort (n=492)

Multicenter

No

Structured PICO

Does edoxaban reduce the cumulative incidence of acute kidney injury within 1 year compared with apixaban and rivaroxaban in patients with nonvalvular atrial fibrillation?

P

Population

492 adult patients (median age 72 years, 38.0% female) with nonvalvular atrial fibrillation newly initiated on edoxaban, apixaban, or rivaroxaban at a single center in Japan, followed for up to 1 year.

E

Exposure

Edoxaban, apixaban, or rivaroxaban (newly initiated oral factor Xa inhibitor therapy)

C

Comparator

Head-to-head comparison among the three direct oral anticoagulants, with edoxaban serving as the primary reference group against apixaban and rivaroxaban

O

Outcome

Cumulative incidence of acute kidney injury (AKI), defined by KDIGO criteria as a serum creatinine increase ≥1.5-fold from baseline (assessed as a surrogate marker for anticoagulant-related nephropathy), within 1 year of anticoagulant treatment initiationsafety

Main Result

Hazard Ratio: 2.12 (95% CI 1.12–4.02)

Absolute Event Rate: 23.3% vs 10.8%

p-value: p=0.021

Limitations

Single-center retrospective design with a relatively small sample size, susceptible to selection bias and differential loss to follow-up
Medications prescribed at other institutions were not captured
Possibility of residual unmeasured confounding despite IPTW adjustment and E-value calculation
Urine output was not accounted for in the AKI definition due to inclusion of outpatients, potentially underestimating AKI incidence
Use of CHADS2 score rather than CHA2DS2-VA score to assess ischemic stroke risk
Focused solely on renal safety without evaluating the clinical efficacy of DOACs
Single-center retrospective design and small sample size, potentially introducing selection bias and differential losses to follow-up
Medications prescribed at other institutions were not captured, leaving the possibility of unrecorded prescriptions
Possibility of residual unmeasured confounding factors despite IPTW and E-value calculations
Inability to account for urine output in the AKI definition due to inclusion of outpatients, which may have led to underestimation of AKI incidence
Use of the CHADS2 score rather than the CHA2DS2-VA score, and focus solely on renal safety without evaluating DOAC efficacy

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Implication

In this propensity score-weighted retrospective cohort study of patients with nonvalvular atrial fibrillation, edoxaban was associated with a significantly lower 1-year risk of acute kidney injury compared with apixaban and rivaroxaban.

Abstract

Background Anticoagulant use can cause anticoagulant-related nephropathy (ARN), primarily characterized by acute kidney injury (AKI). The incidence and severity of AKI associated with the use of direct oral anticoagulants (DOACs) remain unclear. Methods This study aimed to examine the incidence of AKI in patients with nonvalvular atrial fibrillation (NVAF) receiving DOACs. This single-center, retrospective cohort study enrolled patients with NVAF who received edoxaban, apixaban, or rivaroxaban between January 2015 and December 2023. The primary outcome was the cumulative incidence of AKI within the first year of treatment. Inverse probability of treatment weighting (IPTW) was applied to adjust for imbalances in the measured confounders between treatment groups. Additionally, outcome regression was conducted including covariates in the weighted Cox proportional hazards model. Results Of the 492 enrolled patients, 307, 112, and 73 received edoxaban, apixaban, and rivaroxaban, respectively. The cumulative incidence of AKI within 1 year of the administration for each of these drugs was 10.8%, 23.3%, and 25.0%, respectively (IPTW-adjusted p < 0.001). In multivariable Cox regression analysis with IPTW adjustment, compared with edoxaban, apixaban and rivaroxaban showed adjusted hazard ratios of 2.12 (95% confidence intervals (CI), 1.12–4.02, p = 0.021) and 2.92 (95% CI, 1.44–5.92, p = 0.003), respectively. Conclusion Edoxaban was associated with a lower risk of AKI than other factor Xa inhibitors.

Discussion

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Cite This Study

Aigami et al. (2026) conducted a cohort in Nonvalvular atrial fibrillation (n=492). Apixaban or Rivaroxaban vs. Edoxaban (reference) was evaluated on Cumulative incidence of acute kidney injury (AKI) within 1 year of treatment initiation (defined as serum creatinine increase >=1.5-fold from baseline) (HR 2.12 (apixaban vs edoxaban); HR 2.92 (rivaroxaban vs edoxaban), 95% CI 1.12-4.02, p=0.021).

synapsesocial.com/papers/6ae28f48cbadf70daf6c44b9 https://doi.org/10.21203/rs.3.rs-10901432/v1

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Comparison of Acute Kidney Injury Risks Between Direct Oral Anticoagulants in Nonvalvular Atrial Fibrillation: A Propensity Score-weighted Retrospective Observational Cohort Study

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Comparison of Acute Kidney Injury Risks Between Direct Oral Anticoagulants in Nonvalvular Atrial Fibrillation: A Propensity Score-weighted Retrospective Observational Cohort Study

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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