Abstract 15192: Effectiveness and Safety of Reduced Dose of Dabigatran for High Bleeding Risk Patient Subgroups With Atrial Fibrillation

Abstract

Off-label reduced dosing of direct oral anticoagulants is common among patients at high bleeding risk with atrial fibrillation (AF), however, outcomes data of reduced dosing are limited. We evaluated the effectiveness and safety of reduced dose of dabigatran [110 mg twice daily (BID)] vs. standard dose [150 mg BID] in high bleeding risk subgroups with AF. We identified adult patients with AF who initiated dabigatran (index date) with creatinine clearance (CrCl) ≥30 mL/min between 2012-2018 from Kaiser Permanente Southern California. Three high bleeding risk subgroups were identified: 1) patients aged ≥80 years; 2) patients with moderate renal impairment (CrCl 30-49 mL/min) regardless of age; or 3) patients with bleeding within 12 months prior to the index date or HAS-BLED score ≥3. Patients were followed through December 2018 for stroke or systemic embolism, major bleeding requiring hospitalization, and all-cause mortality. Cause-specific hazard regression models were used to investigate associations between dabigatran dose and clinical outcomes adjusting for covariates and considering competing risks of death. Among high bleeding risk patients with AF [3,749 aged ≥80 years; 1,716 with moderate renal impairment; 3,051 with recent bleed or high HAS-BLED score], 34% received reduced dose of dabigatran. Patients who received reduced dose were older, had reduced renal function, and had more comorbidities. Compared with standard dose, reduced dose of dabigatran was not associated with an increased risk of stroke or systemic embolism but was associated with lower risk of major bleed in patients aged ≥80 years ( Table ). Reduced dose of dabigatran was also associated with lower risk of mortality among patients aged ≥80 years and patients with moderate renal impairment. A lower risk of bleeds and mortality associated with reduced vs standard dose of dabigatran in high-risk patients with AF suggest a better dosing strategy for these risk groups.