Effect of Renal Function for Excessive Anticoagulation with Warfarin in Patients with Atrial Fibrillation

OBJECTIVE To explore the relationship between the level of estimated glomerular filtration rate(eGFR) and excessive anticoagulation in atrial fibrillation patients treated with warfarin, and to evaluate its predictive value for excessive anticoagulation in atrial fibrillation patients treated with warfarin.

METHODS A total of 838 patients with atrial fibrillation who received warfarin treatment were retrospectively included. International normalized ratio(INR) was measured on the morning of the day following the 7th day of medication for all patients. They were divided into the over-anticoagulation group(173 cases) and the non-over-anticoagulation group(665 cases) based on whether INR was > 3.0 after 7 days of medication. General clinical data of the two groups were analyzed. The value of eGFR level in predicting over-anticoagulation in atrial fibrillation patients receiving warfarin treatment was evaluated using the receiver operating characteristic(ROC) curve. Logistic regression equation was used to analyze the related factors of over-anticoagulation in atrial fibrillation patients receiving warfarin treatment.

RESULTS Patients in the over-anticoagulation group had higher age, number of combined medications, and aspartate transaminase(AST) levels than those in the non-over-anticoagulation group(P<0.05); the proportion of abnormal transaminase and combined use of amiodarone was also higher in the over-anticoagulation group(P<0.05). The body weight, albumin, and eGFR levels of patients in the over-anticoagulation group were lower than those in the non-over-anticoagulation group(P<0.05), and the proportion of diabetes was lower in the over-anticoagulation group(P<0.05). The ROC curve showed that the AUC of eGFR for predicting over-anticoagulation with warfarin was 0.651(95%CI: 0.605−0.696, P<0.001), with a sensitivity of 57.80% and a specificity of 65.86%; at this time, the optimal cut-off value of eGFR for predicting over-anticoagulation was ≤ 70 mL·min^‒1·(1.73 m²)^‒1. Multivariate Logistic regression showed that eGFR ≤ 70 mL·min^‒1·(1.73 m²)^‒1(OR=2.445, 95%CI 1.709−3.498, P<0.001), abnormal transaminase(OR=1.693, 95%CI 1.148−2.496, P=0.008), initial dose of warfarin(OR=1.596, 95%CI 1.065−2.394, P=0.024), and combined use of amiodarone(OR=1.626, 95%CI 1.093−2.419, P=0.016) were independent risk factors for over-anticoagulation at the steady state of warfarin anticoagulation intensity, while diabetes(OR=0.333, 95%CI 0.171−0.694, P=0.003) was a protective factor for over-anticoagulation at the steady state of warfarin anticoagulation intensity.

CONCLUSION The eGFR level is closely related to the occurrence of excessive anticoagulation with warfarin in patients with atrial fibrillation and has certain predictive value for it. INR monitoring should be intensified in patients with eGFR≤70 mL·min^‒1·(1.73 m²)^‒1, abnormal transaminases, high initial dose of warfarin, and concomitant amiodarone to reduce the risk of excessive anticoagulation.