Improvement of HAS-BLED bleeding score predictive capability by changing the definition of renal dysfunction in Japanese atrial fibrillation patients on anticoagulation therapy

Abstract

Background and purpose: Severe chronic kidney disease (CKD) is a risk factor for hemorrhagic events in atrial fibrillation (AF) patients on anticoagulation therapy. We postulated that even moderate CKD may be a risk factor for hemorrhage and this recognition would improve predictive capabilities of hemorrhagic risk stratification models in Japanese patients.

Methods and subjects: In this prospective study, 231 non-valvular AF patients were divided into three groups according to estimated glomerular filtration rate (eGFR) and followed-up for a median of 7.1 years. The clinical endpoint was a major hemorrhagic event (MHE). HAS-BLED score was calculated for the cohort and the predictive capability of the original HAS-BLED score was compared with that in which renal dysfunction was redefined as eGFR<60mL/min/1.73m(2).

Results: Forty-four MHEs occurred during follow-up. Compared to no/mild CKD group (≥60mL/min/1.73m(2)), both moderate (30-59mL/min/1.73m(2)) and severe (<30mL/min/1.73m(2)) CKD groups had higher MHE risks (log rank: both p<0.001). MHE risk of patients with moderate CKD was more than threefold higher than the no/mild CKD group even after adjusting for other risk factors (hazard ratio 3.8, 95% confidence interval 1.7-8.7). The C-statistic in receiver-operating curve analysis was numerically but not significantly superior in modified HAS-BLED score compared to original HAS-BLED score (0.67 and 0.64, respectively; p=0.55). However, using modified HAS-BLED score was associated with significant improvement of net reclassification improvement (0.50, p=0.002) and integrated discrimination improvement (0.033, p=0.043).

Conclusions: Moderate CKD contributes to the risk of future major hemorrhagic events in AF patients. Modification of HAS-BLED score by changing the definition of renal failure markedly improved predictive capability.

Keywords: Anticoagulation; Atrial fibrillation; Chronic kidney disease; Hemorrhagic complication; Warfarin.