Dosing challenges with direct oral anticoagulants in the elderly: a retrospective analysis

Direct oral anticoagulants (DOACs) provide patients with attractive options for anticoagulation in atrial fibrillation (AF). However, dosing these agents in the elderly can be challenging due to factors such as drug interactions, reduced renal function, and less frequent monitoring. This study addressed this challenge by reviewing the dosing of three commonly used DOACs (i.e. apixaban, dabigatran, and rivaroxaban) in elderly patients managed at a pharmacist-run anticoagulation clinic.

This was a single-center, retrospective cohort study. A total of 98 cases of DOAC therapy in patients with AF aged 75 years or older receiving care at a large urban healthcare center were identified via chart review. Dosing of each DOAC was assessed at therapy initiation and throughout treatment whenever a serum creatinine was reported, using the Cockcroft-Gault equation to estimate creatinine clearance (CrCl). Dose excursions (defined as instances where patients were exposed to non-Food and Drug Administration (FDA)-approved doses) were documented in each case. Rationales for dose excursions were determined by study investigators via review of progress notes and categorized using clinical judgement.

Upon therapy initiation apixaban was dosed in accordance with FDA recommendations in 92.9% of patient cases, dabigatran in 91.2% of cases, and rivaroxaban in 86.1% of cases (p = 0.70). FDA-recommended dosing was maintained throughout treatment at the highest rates with dabigatran (88.2% versus 78.6% with apixaban and 58.3% with rivaroxaban; p = 0.01, p = 0.005 for dabigatran versus rivaroxaban). The most common rationales for dose excursion were fluctuation in estimated CrCl near the dosing cutoff, and recommendations from nonpharmacist providers co-managing the patient.

Prescribing and maintaining FDA-recommended doses of DOAC agents in the elderly is more challenging than initially perceived. Fluctuations in renal function, comorbidities, and concomitant antiplatelet use may necessitate more individualized dosing strategies with these agents.