Effect of Renal Function on Dosing of Non–Vitamin K Antagonist Direct Oral Anticoagulants Among Patients With Nonvalvular Atrial Fibrillation

Background: Non–vitamin K antagonist direct oral anticoagulants (DOACs) are fixed-dose regimens indicated for stroke prevention in nonvalvular atrial fibrillation (NVAF) patients. Dose adjustment is necessary among patients with renal insufficiency to optimize efficacy and safety. Objective: To assess DOAC dosing appropriateness and its effect on clinical outcomes in NVAF patients. Methods: Adult NVAF patients with ≥1 DOAC pharmacy claim (January 1, 2013, to December 31, 2014), continuous enrollment for ≥12 months post–index DOAC claim, and documented creatinine clearance within 3 months preindex date in the Optum/Humedica SmartFile database were eligible. DOAC dosage was classified as inappropriate or appropriate by level of renal function, age, and body weight per US prescription information. Cox proportional models were used to assess the risks of bleeding and stroke associated with inappropriate DOAC dosage. Results: Of the 388 eligible patients, 69 (17.8%) were inappropriately dosed, and rivaroxaban had the highest inappropriate dosing rate. Most inappropriately dosed patients were underdosed. Inappropriately dosed patients were more likely to be older, female, and have a body weight of ≤60 kg; they also had higher mean CHA₂DS₂-VASc and Charlson comorbidity index scores (all P < 0.05). Overtreated patients had a higher risk of bleeding (hazard ratio [HR] = 5.4; P = 0.006) than undertreated patients (HR = 3.1; P = 0.025) relative to appropriately dosed patients. However, no significant difference in stroke risk was observed, most likely because very few stroke events were observed in the study. Conclusions: Inappropriate dosing occurred among patients with normal and insufficient renal function. The consideration of clinical factors beyond renal function is necessary to reduce bleeding risk associated with DOAC therapy.