Utilization of Apixaban Pharmacokinetics for Dose Optimization in High-Risk Elderly Patients

Background and Objective: Direct oral anticoagulants have largely replaced vitamin K antagonists, for example, warfarin, because of their favorable safety profile and predictable pharmacokinetics, with apixaban being the most widely used direct oral anticoagulant. Although routine therapeutic drug monitoring is not required, measuring apixaban plasma concentrations may be useful in high-risk clinical scenarios. This aim of this study was to evaluate the impact of a repeat apixaban concentration measurement combined with a pharmacokinetic analysis and dose adjustment on drug concentrations and clinical outcomes. Methods: We conducted a retrospective observational cohort study at Hadassah Mount Scopus Hospital, including elderly patients hospitalized between January 2020 and September 2024 with prescriptions for apixaban. Patients with two appropriately timed, maximum apixaban plasma concentrations within 90 days were analyzed. Results: A total of 127 patients were included (median age 79 years, maximum age 97 years; 51% female). At baseline, 16% had subtherapeutic apixaban plasma concentrations and 20% had supratherapeutic concentrations. Female sex was associated with subtherapeutic concentrations while a standard dose (10 mg/day) of apixaban was associated with supratherapeutic plasma concentrations. Dose adjustment was more common in patients with standard dose therapy and in patients with an out-of-range baseline apixaban measurement with adjusted odds ratio of 6.1 and 95% confidence interval of 2.2–16.9 and 4.9 (95% confidence interval 1.9–12.7), respectively. In patients who had undergone repeated apixaban maximum plasma concentration measurements, we found 24 bleeding events and six thrombotic or embolic events within a 1-year follow-up from the second maximum plasma concentration measurement. Bleeding events were more common in patients whose maximum plasma concentration was out of the therapeutic range (28% vs 15%), Conclusions: Dose adjustment based on apixaban plasma concentration monitoring increased the proportion of patients who have apixaban concentrations within the therapeutic range. In high-risk elderly patients, an apixaban concentration measurement coupled with active intervention (e.g., dose adjustment) is likely to be clinically beneficial in avoiding bleeding and thromboembolic events.