Association Between the Change in Total Bilirubin and Risk of Bleeding Among Patients With Nonvalvular Atrial Fibrillation Taking Dabigatran

There is still a lack of effective biomarkers for the prediction of the risk of bleeding events among patients with nonvalvular atrial fibrillation (NVAF) taking dabigatran. This study aimed to investigate the association between change in total bilirubin (CTBIL) and risk of bleeding among patients with NVAF taking dabigatran. The CTBIL was the difference in serum total bilirubin at out of follow-up from baseline serum total bilirubin. A total of 486 patients with NVAF treated with dabigatran (110 mg twice daily) were recruited from 12 centers in China from February 2015 to December 2017. All patients were followed for 3 months. Cox proportional hazards regression analysis was used to evaluate the association between the CTBIL and bleeding. Moreover, a Cox proportional hazards regression with cubic spline functions and smooth curve fitting (the penalized spline method) and 2 piecewise Cox proportional hazards models were used to address the nonlinearity between CTBIL and bleeding. The mean (SD) follow-up duration was 81.2 (20.2) days. In all, 67 patients experienced bleeding events. A U-shaped association was observed between the CTBIL and bleeding, with increased hazard ratios (HRs) in relation to either low or high CTBIL levels. For CTBIL <6.63 µmol/L, the HR (95% confidence interval [CI]) was 0.90 (0.84-0.96), and for CTBIL ≥6.63 µmol/L, the HR (95% CI) was 1.35 (1.14-1.60). Our findings showed a U-shaped relationship between CTBIL and bleeding. Both low and high levels of CTBIL were associated with a higher risk of bleeding.