L-shaped association between gamma-glutamyl transferase-to-albumin ratio and dabigatran-related bleeding in non-valvular atrial fibrillation patients: a multicenter cohort study.

Background: The correlation between the gamma-glutamyl transferase-to-albumin ratio (GAR) and the risk of bleeding in patients with non-valvular atrial fibrillation (NVAF) undergoing treatment with the dabigatran anticoagulant is poorly understood. This study aims to explore whether GAR is associated with bleeding events among patients with NVAF receiving dabigatran anticoagulant therapy.

Methods: We conducted a multicenter, observational cohort study in 12 Chinese hospitals from six provinces, including Beijing, Shanghai and Guangzhou, to evaluate the effectiveness and safety of dabigatran (110 mg) treatment in NVAF patients who were consecutively enrolled during February 2015 and December 2017. All patients had completed a 3-month follow-up period. The baseline variable of interest was the GAR, and the outcome variable was the occurrence of bleeding events. Both univariate and multivariate Cox proportional hazard models were used to evaluate the relationship between GAR and bleeding outcome.

Results: This prospective cohort study included a total of 834 patients (mean age 65.6±11.1 years; 56.8% male). Overall, 82 subjects experienced bleeding. The patients were categorized based on the tertiles of the GAR. Participants in tertile 2 (0.59-1.03) [hazard ratio (HR): 0.28; 95% confidence interval (CI): 0.14-0.55; P<0.001] and tertile 3 (≥1.04) (HR: 0.47; 95% CI: 0.25-0.89; P=0.02) exhibited a lower rate of bleeding compared to the reference group (T1: ≤0.58). Multivariable models with restricted cubic splines demonstrated a nonlinear relationship between GAR and bleeding outcome, with a GAR inflection point of 0.68. The HR (95% CI) was 0.05 (0.01-0.31) (P=0.002) for GAR values <0.68 and 0.96 (0.70-1.31) (P=0.78) for GAR values ≥0.68. Moreover, the correlation between decreased GAR and an increase in bleeding events remained consistent across various subgroups.

Conclusions: GAR is a prevalent, independent predictor of dabigatran-related bleeding in NVAF patients. Moreover, a significant L-shaped association between GAR and bleeding events has been observed.