2025 Southeastern Residency Conference

Title:Evaluation of Safety and Efficacy of Rivaroxaban for Peripheral 
Artery Disease in Patients with Renal Dysfunction


Authors: Persia S. Nelson,  Laura Leigh Stoudenmire


Background: Rivaroxaban, a renally-cleared direct-acting oral anticoagulant (DOAC), has obtained FDA approval for patients with stable PAD. Guidelines for the Management of Lower Extremity PAD recommend rivaroxaban 2.5 mg twice a day combined with low-dose aspirin to prevent major adverse cardiovascular events and major adverse limb events in patients with PAD who are not at an increased risk for bleeding. While patients who are at an increased risk of bleeding are not clearly defined in the guidelines, the safety and efficacy of rivaroxaban in patients with renal dysfunction remains an area of clinical concern. The COMPASS and VOYAGER PAD trials, which assessed the use of rivaroxaban for the treatment of PAD, excluded patients with severe kidney impairment. Related trials discussing DOAC use in patients with chronic kidney disease (CKD) showed increased risk of clotting and bleeding in patients with renal dysfunction. Similar trials have also historically excluded patients with severe kidney impairment. Additionally, drug information resources have advised against the use of rivaroxaban in patients indicated for PAD with CrCl < 15 mL/min as the risk benefit associated with rivaroxaban use in patients with CrCl < 15 mL/min is uncertain.   


Methods: The purpose of this study was to assess the safety and efficacy of rivaroxaban in patients with renal dysfunction. This retrospective cohort study consisted of patients receiving rivaroxaban 2.5 mg BID with a diagnosis of PAD. Patients were eligible for inclusion if they were adults age 18 and older with a diagnosis of PAD and received rivaroxaban 2.5 mg twice daily from January 1, 2019 to June 30, 2024. Exclusion criteria consisted of pregnant patients, patients with a past medical history of hemorrhagic or ischemic cerebral infarction, active peptic ulcer disease with recent bleeding, and active bleeding prior to initiation of rivaroxaban 2.5 mg BID for PAD. Patients were divided into two groups being CrCl < 15 mL/min and CrCl > 15 mL/min. The primary endpoint was major bleeding events which was defined as a > 2 g/dL decrease in hemoglobin, documented transfusion > 2 units of packed red blood cells, or bleeding of a critical anatomical site (e.g intracranial, spinal, ocular) within 90 days post discharge with rivaroxaban. The secondary endpoint included efficacy and was assessed by evaluating the onset of myocardial infarction, ischemic stroke, acute limb ischemia, major amputation, or cardiovascular death within 90 days post discharge. Additionally, the secondary outcome included bleeding readmission within 90 days.


Results: The primary and secondary composite outcomes were not statistically significant between the CrCl < 15 mL/min group and CrCl > 15 mL/min. In reference to the primary outcome, bleeding events had a composite P-value of 0.69. Regarding the secondary outcomes, bleeding readmission had a composite P-value of 0.1 while major adverse cardiac events had a composite P-value of 0.37.    


Conclusion: Despite the lack of statistical significance between the groups, further research is necessary to evaluate the safety and efficacy of rivaroxaban in patients with reduced renal function.