Effectiveness and safety of Dabigatran 110 mg versus 150 mg for Stroke Prevention in Patients with Atrial Fibrillation at High Bleeding Risk.

Purpose: The effectiveness and tolerability of a reduced dose (110 mg) of dabigatran versus the standard dose (150 mg) were evaluated in subgroups of patients with atrial fibrillation (AF) at high bleeding risk.

Methods: Eligible patients were adults with AF and a creatinine clearance rate ≥30 mL/min who were initiated on treatment with dabigatran (index) between 2016 and 2018. High-bleeding-risk subgroups were identified: (1) age ≥80 years; (2) moderate renal impairment (creatinine clearance rate 30-<50 mL/min); and (3) recent bleeding or a HAS-BLED score of ≥3. Fine-Gray subdistribution hazard regression models with inverse probability of treatment weights were used to investigate associations between dabigatran dose and three outcomes: stroke or systemic embolism, major bleeding requiring hospitalization, and all-cause mortality.

Findings: Among 7858 patients with AF and a high bleeding risk (age ≥80 years, 3472; moderate renal impairment, 1574; recent bleeding or HAS-BLED score ≥3, 2812), 32.3% received reduced-dose dabigatran. Compared with the standard dose, use of the reduced dose of dabigatran was not associated with an increased risk for stroke or systemic embolism but was associated with a lower risk for major bleeding (HR = 0.65; 95% CI, 0.44-0.95) and all-cause mortality (HR = 0.78; 95% CI, 0.65-0.92) in patients aged ≥80 years. The use of reduced-dose dabigatran was associated with a lower risk for major bleeding (HR = 0.54; 95% CI, 0.30-0.95) and all-cause mortality among patients with moderate renal impairment (HR = 0.53; 95% CI, 0.40-0.71).

Implications: Lower risks for bleed and mortality associated with reduced- versus standard-dose dabigatran in patients with AF and a high bleeding risk suggest a better dosing strategy.