Clinical Patterns and Appropriateness of Apixaban Dosing in Patients With Atrial Fibrillation

BACKGROUND: Apixaban is a direct oral anticoagulant for stroke prevention in patients with atrial fibrillation (AF) or atrial flutter (AFL), with dose reduction being recommended based on age, body weight, and creatinine. OBJECTIVES: The objective of the study was to describe the use and appropriateness of reduced-dose apixaban. METHODS: Using electronic health record data from PCORnet health systems in the United States, patients with AF/AFL treated with apixaban between 2015 and 2019 were identified. Patients were categorized by dose and appropriateness of dose reduction. Exploratory outcomes included death, ischemic stroke, hemorrhagic stroke, intracranial hemorrhage, and major bleeding. RESULTS: Among 280,709 patients with AF/AFL, 45,947 (16.4%) received apixaban (84.6% full-dose; 15.4% reduced-dose). Among reduced-dose recipients, 61.0% did not meet the criteria for dose reduction. Over a median follow-up of 2.2 years, reduced-dose patients had higher unadjusted event rates than full-dose patients, including death, ischemic stroke, and major bleeding. Compared with those on appropriate full-dose apixaban as the reference group, inappropriate low-dose apixaban was associated with higher mortality (adjusted HR: 1.77; 95% CI: 1.66-1.88), whereas differences in ischemic stroke (adjusted HR: 1.05; 95% CI: 0.90-1.23), intracranial hemorrhage (adjusted HR: 0.95; 95% CI: 0.71-1.28), and major bleeding (adjusted HR: 1.02; 95% CI: 0.89-1.17) were attenuated. CONCLUSIONS: In clinical practice, reduced-dose apixaban accounts for approximately 15% of prescriptions, with the majority (61%) prescribed in individuals who do not meet the labeling criteria for dose reduction.