Dataset Information

Incremental Value of Genotype Bins over the HAS-BLED Score for the Prediction of Bleeding Risk in Warfarin-Treated Patients with Atrial Fibrillation.

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.

SUBMITTER: Liu J

PROVIDER: S-EPMC8632379 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Several bleeding risk assessment models have been developed in atrial fibrillation (AF) patients with oral anticoagulants, but the most appropriate tool for predicting bleeding remains uncertain. Therefore, we aimed to assess the diagnostic accuracy of the Hypertension, Abnormal liver/renal function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly, Drugs/alcohol concomitantly (HAS-BLED) score compared with other risk scores in anticoagulated patients with AF. Methods: We comprehensively searched the PubMed and Embase databases until July 2021 to identify relevant pieces of literature. The predictive abilities of risk scores were fully assessed by the C-statistic, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) values, calibration data, and decision curve analyses. Results: A total of 39 studies met the inclusion criteria. The C-statistic of the HAS-BLED score for predicting major bleeding was 0.63 (0.61-0.65) in anticoagulated patients regardless of vitamin k antagonists [0.63 (0.61-0.65)] and direct oral anticoagulants [0.63 (0.59-0.67)]. The HAS-BLED had the similar C-statistic to the Hepatic or renal disease, Ethanol abuse, Malignancy, Older, Reduced platelet count or function, Re-bleeding risk, Hypertension (uncontrolled), Anemia, Genetic factors, Excessive fall risk, Stroke (HEMORR2HAGES), the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA), the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT), the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF), or the Age, Biomarkers, Clinical History (ABC) scores, but significantly higher C-statistic than the Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, Stroke/transient ischemic attack history (CHADS2) or the Congestive heart failure/left ventricular ejection fraction ≤ 40%, Hypertension, Age ≥75 years, Diabetes mellitus, Stroke/transient ischemic attack/thromboembolism history, Vascular disease, Age 65-74 years, Sex (female) (CHA2DS2-VASc) scores. NRI and IDI values suggested that the HAS-BLED score performed better than the CHADS2 or the CHA2DS2-VASc scores and had similar or superior predictive ability compared with the HEMORR2HAGES, the ATRIA, the ORBIT, or the GARFIELD-AF scores. Calibration and decision curve analyses of the HAS-BLED score compared with other scores required further assessment due to the limited evidence. Conclusion: The HAS-BLED score has moderate predictive abilities for bleeding risks in patients with AF regardless of type of oral anticoagulants. Current evidence support that the HAS-BLED score is at least non-inferior to the HEMORR2HAGES, the ATRIA, the ORBIT, the GARFIELD-AF, the CHADS2, the CHA2DS2-VASc, or the ABC scores.

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