Association between rivaroxaban use and acute kidney injury in patients over 65 years: A large-scale analysis of spontaneous reporting system data

BACKGROUND: Given that long-term anticoagulant therapy is required in many clinical scenarios, continuous safety monitoring of direct factor Xa inhibitors is of great importance. To date, the renal safety of these agents remains a subject of debate. OBJECTIVES: The aim of this study was to assess the association between direct factor Xa inhibitors and acute kidney injury (AKI) using data from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). MATERIAL AND METHODS: The study period extended from the first quarter of 2014 to the last quarter of 2024, and reports of adverse events (AEs) related to rivaroxaban and apixaban were extracted separately from FAERS. The association between direct factor Xa inhibitors and AKI was evaluated using disproportionality analysis methods. RESULTS: Rivaroxaban-associated AKI was more common in men, and the risk was higher among patients older than 65 years. Rivaroxaban showed a significant positive signal for AKI in patients older than 65 years, with a reported reporting odds ratio (ROR) of 3.82 (95% confidence interval (95% CI): 3.65-4.01), proportional reporting ratio (PRR) of 3.78, EBGM05 of 3.68, and IC025 of 1.88. In comparison, apixaban showed no significant risk signal, with an ROR of 0.86 (95% CI: 0.79-0.94), PRR of 0.86, EBGM05 of 0.86, and IC025 of -0.34. Acute kidney injury typically occurred at a median of 109 days after treatment initiation, with approx. 50% of cases occurring within the first 3 months. The main outcomes of AKI were hospitalization (56.06%) and death (37.67%). CONCLUSIONS: Our findings suggest a significant association between rivaroxaban use and AKI in elderly patients. Clinical monitoring of renal function should be intensified in elderly patients receiving rivaroxaban. However, it should be emphasized that this study presents only disproportionality analysis results and cannot establish a causal relationship between rivaroxaban and AKI. Therefore, the findings should be interpreted with caution.