17-06: Reduced Dose Dabigatran, Rivaroxaban, and Apixaban in Patients without Severe Renal Impairment: Effectiveness and Safety

Purpose of the study: The introduction of non-vitamin K antagonist oral anticoagulants (NOACs) has been a major advance for stroke prevention in atrial fibrillation. Because NOACs have significant renal clearance, dose reduction is needed in patients with severe kidney disease. However, some physicians may prescribe reduced-dose NOACs to patients with relatively good renal function due to the concerns over bleeding risk. We sought to investigate the use and clinical outcomes of reduced-dose NOACs in patients without severe renal impairment. Methods: We performed a retrospective cohort analysis using a large U.S. commercial insurance database, OptumLabs Data Warehouse. Patients receiving reduced- and standard-dose NOACs were matched on socio-demographic characteristics, comorbidities, prior warfarin use and the use of concomitant P-gp and CYP3A4 inhibitors. Cox proportional hazard regression was used to compare the risk of stroke and major bleeding between patients received reduced- and standard-dose NOACs. Results: We identified 12,593 patients with nonvalvular atrial fibrillation who received NOACs but did not have any renal indication for dose adjustment. We defined a renal indication for dose reduction as: dabigatran users with GFR <30 mL/min/1.73m2, rivaroxaban users with GFR <50 mL/min/1.73m2, and apixaban users with creatinine ≥1.5 mg/dL. Approximately 1 in 8 patients who did not have a renal indication for dose reduction received a low-dose NOAC (dabigatran: 8.2%; rivaroxaban: 14.9 %; apixaban: 15.4%). Older patients, females, and patients with higher stroke and bleeding risk at baseline were more likely to receive a reduced dose. In patients receiving dabigatran and apixaban, a reduced dose was associated with an increased risk of stroke (Hazard ratio [HR] 2.64 [1.01–6.89]), but little change in the risk of major bleeding (HR: 1.22 [0.67–2.23]). In patients receiving rivaroxaban, no relationship was observed between doses and the risk of stroke or major bleeding. Conclusions: Reducing dabigatran and apixaban doses in patients without severe renal impairment may be related to reduced effectiveness without any improvement in safety. Unnecessary dose reduction may lead to excessive avoidable strokes.