Abstract
Background This study aimed to analyse the role of the HAS-BLED score with the addition of genotype bins for bleeding risk prediction in warfarin-treated patients with atrial fibrillation (AF). Methods and Results Consecutive patients with AF on initial warfarin treatment were recruited. For each patient, CYP2C9∗3 and VKORC1-1639 A/G genotyping was performed to create 3 genotype functional bins. The predictive values of the HAS-BLED score with or without the addition of genotype bins were compared. According to the carrier status of the genotype bins, the numbers of normal, sensitive, and highly sensitive responders among 526 patients were 64 (12.17%), 422 (80.23%), and 40 (7.60%), respectively. A highly sensitive response was independently associated with clinically relevant bleeding (HR: 3.85, 95% CI: 1.88–7.91, P=0.001) and major bleeding (HR:3.75, 95% CI: 1.17–11.97, P=0.03). With the addition of genotype bins, the performance of the HAS-BLED score for bleeding risk prediction was significantly improved (c-statistic from 0.60 to 0.64 for clinically relevant bleeding and from 0.64 to 0.70 for major bleeding, P < 0.01). Using the integrated discriminatory, net reclassification improvement, and decision curve analysis, the HAS-BLED score plus genotype bins could perform better in predicting any clinically relevant bleeding than the HAS-BLED score alone. Conclusions Genotypes have an incremental predictive value when combined with the HAS-BLED score for the prediction of clinically relevant bleeding in warfarin-treated patients with AF.
Highlights
Patients with atrial fibrillation (AF) are at a high risk for stroke and systemic embolism, which could be substantially reduced with the administration of oral anticoagulants, including vitamin K antagonists and nonvitamin K antagonist oral anticoagulants (NOACs) [1,2,3]
A total of 526 patients with AF who were on warfarin were recruited; among them, 290 (55.13%) were male, and the mean age was 60.63 ± 11.05 years. e average stable therapeutic dose of warfarin was 2.89 ± 1.06, and 143 (27.18%) patients had a therapeutic range (TTR) of
After multiple logistic regression analysis, both highly sensitive responders and the HASBLED score were independent risk factors for major bleeding (HR: 3.75, 95% CI: 1.17–11.97, P 0.001; HR:3.93, 95% CI: 1.52–10.16, P 0.005) and any clinically relevant bleeding (HR: 3.85, 95% CI: 1.88–7.91, P 0.001; HR:2.75, 95% CI: 1.60–4.74, P 0.001) (Table 3)
Summary
Patients with atrial fibrillation (AF) are at a high risk for stroke and systemic embolism, which could be substantially reduced with the administration of oral anticoagulants, including vitamin K antagonists and nonvitamin K antagonist oral anticoagulants (NOACs) [1,2,3]. Erefore, early prediction of the poor control of warfarin anticoagulation is vital for personalized selection between warfarin and NOACs in AF patients who need anticoagulation treatment [9]. E HAS-BLED bleeding risk score (hypertension (systolic blood pressure >160 mmHg), abnormal liver/renal function (creatinine ≥200 μmol/L), stroke, bleeding history or predisposition, labile international normalized ratio (INR) (INR in Cardiology Research and Practice range 65), and concomitant drugs/alcohol) [10, 11] is the most widely validated model in AF and non-AF populations [12]. Further validation studies have confirmed that the HAS-BLED score is an effective predictor of bleeding in warfarin-naive patients and in those administered warfarin plus aspirin or nonwarfarin treatment [14, 15]. The predictive capacity of the HAS-BLED score for bleeding risk in warfarinanticoagulated patients remains modest even with the incorporation of the labile INR [14, 19]
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