Title: Evaluation of apixaban dosing strategies for venous thromboembolism in patients receiving hemodialysis
Authors: Hayden Caldwell, Blake Sloan, Ryan Tilton, Ryan Imel, Grace Barr, Caitlin Hastings, & Brittney Bright
Background: Venous thromboembolism (VTE) is categorized as deep venous thromboembolism (DVT) or pulmonary embolism (PE) caused by the formation of a thrombus in the veins of the lower extremities or pulmonary arteries. Apixaban is a factor Xa inhibitor approved for the indication of VTE treatment. Apixaban is mainly metabolized by CYP3A4 with other CYP enzymes contributing to minor metabolism. Apixaban is 87% protein bound and approximately 27% renally eliminated. However, patients with end stage renal disease (ESRD) receiving hemodialysis were not included in initial trials which established dosing. Existing literature is limited regarding whether to omit or include the loading dose of apixaban (10mg twice daily for 7 days) in this patient population. Given that a percentage of apixaban is renally cleared, there is concern regarding an increased bleed risk in patients with ESRD on HD receiving the standard loading dose. Current clinical practice varies and may be influenced by provider preference.
Methods: This study evaluated the safety and efficacy of the apixaban loading dose versus no loading dose in patients with ESRD on hemodialysis receiving treatment for VTE. We conducted a multi-center, retrospective cohort study at North Carolina Baptist Hospital and Atrium Health High Point Medical Center. Eligible patients included adults who have ESRD receiving hemodialysis and developed a VTE treated with apixaban from April 2024 to October 2025. Patients were excluded if they had antiphospholipid syndrome, received concurrent CYP3A4 inducers/inhibitors, received continuous renal replacement therapy, received apixaban 2.5mg, or received greater than or equal to seven days of parenteral anticoagulation prior to starting apixaban. The primary outcome was the incidence of recurrent VTE or progression of DVT to PE within 90 days after apixaban initiation. Secondary outcomes were the occurrence of major bleeding and clinically relevant non-major bleeding within 14 days of apixaban initiation defined by the International Society on Thrombosis and Haemostasis . Statistical analyses included descriptive statistics using t-test for continuous variables, Fischer’s exact test for categorical variables, and mean and interquartile range for various characteristics.
Results: There were 30 patients included in this study, 18 patients in the apixaban load group, and 12 patients in the apixaban no-load group. The most common reason for not being included in this study was receipt of parenteral agents for greater than seven days and chronic VTE. There were more patients in the apixaban load group with liver disease with seven in the load group and one in the no load group. Overall, comorbidities were similar between the two groups except there were more patients in the load group that had liver disease with seven patients in the load group and one patient in the no load group. The primary outcome was incidence of recurrent VTE or progression of DVT to PE, which occurred in one (5.6%) patient in the apixaban load group and zero (0.0%) in the apixaban no-load group. The secondary outcome of occurrence of major bleeding within 14 days occurred in two (11.1%) patients in the apixaban load group and zero (0.0%) in the apixaban no load group. The other secondary outcome of clinically relevant non-major bleeding within 14 days occurred in one (5.6%) patient in the apixaban load group and one (8.3%) patient in the no load group.
Conclusion: The results of this study were inconclusive due to the small sample size and low incidence of outcomes. The overall low sample size limited the ability to perform appropriate statistical analysis. The observed data showed a possible increased incidence of major bleeding events, but statistical significance is indeterminant. Further studies with larger sample sizes are needed to determine any changes needed in clinical practice.
