Background: Dabigatran etexilate (DE) has similar stroke prevention efficacy in patients with and without diabetes mellitus (DM). However, the benefit of reducing major bleeding was not seen in diabetics. Thus, this study investigated anticoagulant responses to DE and the biological predictors of this response in a DM model.
Methods: Experiments were performed in six control (C), eight DE-treated control (CD), five diabetic (D), and eight DE-treated diabetic (DD) rats. Dabigatran etexilate (50 mg/kg/day) was administered in chow for 12 weeks. At the end of the study, plasma glucose, triglycerides, total cholesterol (TC), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), and plasma creatinine were measured. Correlations were ascertained with the diluted thrombin time (dTT).
Results: When corrected for similar DE intake, dTT was significantly higher in DD than CD rats (P < 0.001). There was a significant negative correlation between creatinine clearance (CCr) and dTT (r = -0.91, P < 0.01) in DD rats. In addition, dTT was positively correlated with TC (r = 0.96, P < 0.01), LDL-C (r = 0.75, P = 0.04), and glucose (r = 0.83, P = 0.02). In multiple regression analysis, CCr (r = -0.81, P = 0.01), TC (r = 0.93, P < 0.001), and LDL-C (r = 0.74, P < 0.01) remained the only independent predictors of dTT.
Conclusions: The results show a significantly more intense DE-induced anticoagulation in diabetic rats that does not seem to be solely related to altered kidney function, and demonstrate that plasma cholesterol can significantly affect DE anticoagulation in this setting.
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