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

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.

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P4748HASBLED score, frailty index or comorbidity index for bleeding risk assessment in patients with atrial fibrillation?

European Heart Journal ◽

10.1093/eurheartj/ehz745.1124 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

L Fauchier ◽

A Bisson ◽

A Bodin ◽

N Clementy ◽

B Pierre ◽

...

Keyword(s):

Atrial Fibrillation ◽

Elderly Patients ◽

Major Bleeding ◽

Frailty Index ◽

Bleeding Risk ◽

Risk Scores ◽

P Value ◽

Bleeding Events ◽

Predictive Values ◽

Comorbidity Index

Abstract Background Charlson comorbidity index (CCI) is a tool to measure comorbid disease status and a strong estimator of mortality. The quantifiable frailty phenotype has also been validated as predictive of mortality and disability. Claims data can be used to classify individuals as frail and non-frail using the Claims-based Frailty Index (CFI). We evaluated whether these tools may help to predict the risk of bleeding in patients with atrial fibrillation (AF). Methods All patients with AF seen in an academic institution were identified and followed up for mortality, stroke and bleeding events. HAS-BLED, HEMORR2HAGES, ATRIA and ORBIT scores, CCI and CFI were calculated for each patient. Hazard ratios were calculated and predictive abilities of the scores were compared using the c-statistic in the whole population and then separately in elderly patients (>75 yo). Results Among 8962 patients with AF, 274 major bleeding events were recorded during a follow-up of 874±1054 days. Bleeding occurred more commonly in patients with higher bleeding risk scores, CCI and CFI. The 4 bleeding risk scores significantly had lower c-statistics than CCI and CFI for predicting major bleeding (table). Results were similar whether patients were treated with OAC or no OAC. In elderly patients, the c-statistics were all lower and were not significantly different for the 4 scores, CCI and CFI scores (0.594, 0,572, 0.595, 0.594, 0.616 and 0.591 for HAS-BLED, HEMORR2HAGES, ATRIA, ORBIT, CCI and CFI, respectively). Predictive values for major bleeding ROC Area 95% Conf. Interval P value vs CCI/CFI HASBLED 0.588 0.555–0.621 0.002/0.003 HEMORR2HAGES 0.564 0.531–0.598 <0.0001/<0.0001 ATRIA 0.559 0.522–0.595 <0.0001/<0.0001 ORBIT 0.577 0.542–0.612 0.0002/0.0003 Charlson, CCI 0.652 0.619–0.684 –/0.58 Frailty index, CFI 0.648 0.615–0.681 0.58/– Conclusion Comorbidities and frailty, respectively assessed with CCI and CFI, demonstrated statistically better performances in predicting major bleeding than the 4 established bleeding risk scores in AF, although all c-indexes were broadly similar. The 4 bleeding risk scores, CCI and CFI showed lower performance in predicting bleeding within elderly patients in whom they all performed equally to predict bleeding events. Given their simplicity and similar performances, the user-friendly bleeding risk scores remain attractive tools for the estimation of bleeding risk in elderly patients with AF.

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Use of Simplified HAS-BLED Score for Predicting Bleeding Events in Anticoagulated Patients with Atrial Fibrillation

Journal of the Medical Association of Thailand ◽

10.35755/jmedassocthai.2021.05.12142 ◽

2021 ◽

Vol 104 (5) ◽

pp. 802-806

Keyword(s):

Atrial Fibrillation ◽

Risk Prediction ◽

Major Bleeding ◽

Predictive Value ◽

Statistical Significance ◽

Bleeding Risk ◽

Minor Bleeding ◽

Bleeding Events ◽

Sensitivity Specificity ◽

Anticoagulated Patients

Objective: To demonstrate bleeding risk prediction of simplified HAS-BLED (sHAS-BLED) score in anticoagulated patients with atrial fibrillation (AF). Materials and Methods: AF patients receiving warfarin were retrospectively recruited in Central Chest Institute of Thailand between October 2012 and December 2017. The main outcome was total bleeding including major bleeding, clinically relevant non-major bleeding or minor bleeding. The chi-square test or Fisher’s exact test was used to compare the main outcome between sHAS-BLED and conventional HAS-BLED (cHAS-BLED) scores. A sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of sHAS-BLED were calculated. The discrimination performances of sHAS-BLED and cHAS-BLED scores were demonstrated with c-statistics. Results: One hundred ten patients were recruited. The mean age was 70.53±9.58 years. The average sHAS-BLED and cHAS-BLED scores were 2.23±0.79 and 1.95±0.83, respectively. The patients with sHAS-BLED score of 3 or more had 15 total bleeding events (37.50%) while those with score of less than 3 had 13 total bleeding events (18.57%). Those with sHAS-BLED score of 3 or more had more total bleeding than those with score of less than 3 with statistical significance (odds ratio 2.63; 95% CI 1.09 to 6.25; p=0.049). A sensitivity, specificity, PPV, and NPV of sHAS-BLED score were 53.57%, 69.51%, 37.50%, and 81.43%, respectively. The discrimination performances of sHAS-BLED and cHAS-BLED scores were demonstrated with c-statistics of 0.65 and 0.67, respectively. Conclusion: The sHAS-BLED score can be used for bleeding risk prediction in anticoagulated AF patients compared with cHAS-BLED score. Keywords: Simplified HAS-BLED, Atrial fibrillation, Anticoagulant, Bleeding, SAMe-TT₂R₂

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Composite risk scores and composite endpoints in the risk prediction of outcomes in anticoagulated patients with atrial fibrillation

Thrombosis and Haemostasis ◽

10.1160/th13-12-1033 ◽

2014 ◽

Vol 111 (03) ◽

pp. 549-556 ◽

Cited By ~ 16

Author(s):

Amitava Banerjee ◽

Laurent Fauchier ◽

Anne Bernard-Brunet ◽

Nicolas Clementy ◽

Gregory Y. H. Lip

Keyword(s):

Atrial Fibrillation ◽

Risk Prediction ◽

Major Bleeding ◽

Predictive Value ◽

Risk Scores ◽

Chads2 Score ◽

Net Reclassification Improvement ◽

Composite Endpoints ◽

Composite Risk ◽

Anticoagulated Patients

SummarySeveral validated risk stratification schemes for prediction of ischaemic stroke (IS)/thromboembolism (TE) and major bleeding are available for patients with non-valvular atrial fibrillation (NVAF). On the basis for multiple common risk factors for IS/TE and bleeding, it has been suggested that composite risk prediction scores may be more practical and user-friendly than separate scores for bleeding and IS/TE. In a long-term prospective hospital registry of anticoagulated patients with newly diagnosed AF, we compared the predictive value of existing risk prediction scores as well as composite risk scores, and also compared these risk scoring systems using composite endpoints. Endpoint 1 was the simple composite of IS and major bleeds. Endpoint 2 was based on a composite of IS plus intracerebral haemorrhage (ICH). Endpoint 3 was based on weighted coefficients for IS/TE and ICH. Endpoint 4 was a composite of stroke, cardiovascular death, TE and major bleeding. The incremental predictive value of these scores over CHADS2 (as reference) for composite endpoints was assessed using c-statistic, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Of 8,962 eligible individuals, 3,607 (40.2%) had NVAF and were on OAC at baseline. There were no statistically significant differences between the c-statistics of the various risk scores, compared with the CHADS2 score, regardless of the endpoint. For the various risk scores and various endpoints, NRI and IDI did not show significant improvement (≥1%), compared with the CHADS2 score. In conclusion, composite risk scores did not significantly improve risk prediction of endpoints in patients with NVAF, regardless of how endpoints were defined. This would support individualised prediction of IS/TE and bleeding separately using different separate risk prediction tools, and not the use of composite scores or endpoints for everyday ‘real world’ clinical practice, to guide decisions on thromboprophylaxis.Note: The review process for this paper was fully handled by Christian Weber, Editor in Chief.

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Major bleeding and intracranial hemorrhage risk prediction in patients with atrial fibrillation: Attention to modifiable bleeding risk factors or use of a bleeding risk stratification score? A nationwide cohort study

International Journal of Cardiology ◽

10.1016/j.ijcard.2017.11.025 ◽

2018 ◽

Vol 254 ◽

pp. 157-161 ◽

Cited By ~ 30

Author(s):

Tze-Fan Chao ◽

Gregory Y.H. Lip ◽

Yenn-Jiang Lin ◽

Shih-Lin Chang ◽

Li-Wei Lo ◽

...

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Cohort Study ◽

Risk Stratification ◽

Risk Prediction ◽

Intracranial Hemorrhage ◽

Major Bleeding ◽

Bleeding Risk ◽

Hemorrhage Risk ◽

Risk Stratification Score

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230 Machine Learning Models for Predicting Ischemic Stroke and Major Bleeding Risk in Patients with Atrial Fibrillation

Heart Lung and Circulation ◽

10.1016/j.hlc.2020.09.237 ◽

2020 ◽

Vol 29 ◽

pp. S137-S138

Author(s):

J. Lu ◽

G. Dwivedi ◽

F. Sanfilippo ◽

M. Bennamoun ◽

J. Hung ◽

...

Keyword(s):

Machine Learning ◽

Atrial Fibrillation ◽

Ischemic Stroke ◽

Major Bleeding ◽

Bleeding Risk ◽

Learning Models ◽

Machine Learning Models

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REAL-WORLD COMPARISON OF MAJOR BLEEDING RISK AMONG UNTREATED NON-VALVULAR ATRIAL FIBRILLATION PATIENTS AND THOSE INITIATING APIXABAN, DABIGATRAN, RIVAROXABAN, OR WARFARIN

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(16)30669-6 ◽

2016 ◽

Vol 67 (13) ◽

pp. 668 ◽

Cited By ~ 1

Author(s):

Alpesh Amin ◽

Allison Keshishian ◽

Lin Xie ◽

Onur Baser ◽

Kwanza Price ◽

...

Keyword(s):

Atrial Fibrillation ◽

Major Bleeding ◽

Real World ◽

Bleeding Risk

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Abstract 140: Comparison of Major Complication of Oral Anticoagulants in Non-Valvular Atrial Fibrillation: Systematic Review and Meta-Analyses

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.37.suppl_1.140 ◽

2017 ◽

Vol 37 (suppl_1) ◽

Author(s):

Hong Seok Lee

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Major Bleeding ◽

Oral Anticoagulant ◽

Stroke Risk ◽

Oral Anticoagulants ◽

Bleeding Risk ◽

Gi Bleeding ◽

Ischemic Stroke Risk ◽

Meta Analyses

Background: Oral anticoagulants known as a novel oral anticoagulant have been used for the management of non -valvular atrial fibrillation. There was no enough study regarding the efficacy and safety of three major new oral anticoagulants. We assessed major three oral anticoagulants in terms of major bleeding complication and stroke prevention by meta-analyses studies comparing those drugs. Method: Relevant studies were identified through electronic literature searches of MEDLINE, EMBASE, Cochrane library, and clinicaltrials.gov (from inception to February 24, 2016). RevMan and ITC software were used for direct comparisons, respectively. Results: Apixaban (N=6020), versus dabigatran(N=12038), apixaban versus rivaroxaban(N=8503) and rivaroxaban versus dabigatran were analyzed directly. There was significantly higher major bleeding risks in apixaban compared to dabigatran (both 110mg and 150mg) after adjusting baseline bleeding risk (Relative risk 3.41, 95% confidence interval(2.61 to 4.47) in 110mg, (5.62, 4.83 to 6.54) in 150mg. Intracranial bleeding risk in apixaban was significantly higher than in dabigatran (10.5, 6.10 to18.01). However, apixaban had less GI bleeding risk compared to dabigatran (0.80 , 0.65 to 0.98) and also had less ischemic stroke risk (0.31,0.22 to 0.42). Rivaroxaban showed higher major bleeding risk than dabigatran 110mg (2.34 , 1.81 to 3.03), however, Rivaroxaban had less bleeding risk compared to dabigatran 150mg (0.41, 0.35 to 0.46). Dabigatran 110mg and 150mg had less GI bleeding risk compared to rivaroxaban (0.31 , 0.24 to 0.39) and (0.23,0.17 to 0.29) respectively. Ischemic stroke risk was also decreased in dabigatran110mg (0.46, 0.38 to 0.57). and 150mg (0.66 ,0.52 to 0.83). Conclusion: Observed oral anticoagulants were associated with various complications. Overall, apixaban had higher intracranial bleeding risk than dabigatran. The highest GI bleeding risk in rivaroxaban compared to apixaban and dabigatran. Ischemic stroke risk was the highest in dabigatran. In conclusion, we may use those oral anticoagulant based on risks rates, however, a larger study with longer follow-up is needed to corroborate findings.

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GARFIELD-AF model for prediction of stroke and major bleeding in atrial fibrillation: a Danish nationwide validation study

BMJ Open ◽

10.1136/bmjopen-2019-033283 ◽

2019 ◽

Vol 9 (11) ◽

pp. e033283 ◽

Cited By ~ 3

Author(s):

Frederik Dalgaard ◽

Karen Pieper ◽

Freek Verheugt ◽

A John Camm ◽

Keith AA Fox ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischaemic Stroke ◽

Major Bleeding ◽

Risk Model ◽

Oral Anticoagulants ◽

External Validation ◽

Bleeding Risk ◽

Risk Scores ◽

Secondary Outcome

ObjectivesTo externally validate the accuracy of the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) model against existing risk scores for stroke and major bleeding risk in patients with non-valvular AF in a population-based cohort.DesignRetrospective cohort study.SettingDanish nationwide registries.Participants90 693 patients with newly diagnosed non-valvular AF were included between 2010 and 2016, with follow-up censored at 1 year.Primary and secondary outcome measuresExternal validation was performed using discrimination and calibration plots. C-statistics were compared with CHA2DS2VASc score for ischaemic stroke/systemic embolism (SE) and HAS-BLED score for major bleeding/haemorrhagic stroke outcomes.ResultsOf the 90 693 included, 51 180 patients received oral anticoagulants (OAC). Overall median age (Q1, Q3) were 75 (66–83) years and 48 486 (53.5%) were male. At 1-year follow-up, a total of 2094 (2.3%) strokes/SE, 2642 (2.9%) major bleedings and 10 915 (12.0%) deaths occurred. The GARFIELD-AF model was well calibrated with the predicted risk for stroke/SE and major bleeding. The discriminatory value of GARFIELD-AF risk model was superior to CHA2DS2VASc for predicting stroke in the overall cohort (C-index: 0.71, 95% CI: 0.70 to 0.72 vs C-index: 0.67, 95% CI: 0.66 to 0.68, p<0.001) as well as in low-risk patients (C-index: 0.64, 95% CI: 0.59 to 0.69 vs C-index: 0.57, 95% CI: 0.53 to 0.61, p=0.007). The GARFIELD-AF model was comparable to HAS-BLED in predicting the risk of major bleeding in patients on OAC therapy (C-index: 0.64, 95% CI: 0.63 to 0.66 vs C-index: 0.64, 95% CI: 0.63 to 0.65, p=0.60).ConclusionIn a nationwide Danish cohort with non-valvular AF, the GARFIELD-AF model adequately predicted the risk of ischaemic stroke/SE and major bleeding. Our external validation confirms that the GARFIELD-AF model was superior to CHA2DS2VASc in predicting stroke/SE and comparable with HAS-BLED for predicting major bleeding.

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Rivaroxaban Versus Warfarin for Management of Obese African Americans With Non-Valvular Atrial Fibrillation or Venous Thromboembolism: A Retrospective Cohort Analysis

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029620954910 ◽

2020 ◽

Vol 26 ◽

pp. 107602962095491

Author(s):

Olivia S. Costa ◽

Jan Beyer-Westendorf ◽

Veronica Ashton ◽

Dejan Milentijevic ◽

Kenneth Todd Moore ◽

...

Keyword(s):

Atrial Fibrillation ◽

Venous Thromboembolism ◽

African Americans ◽

Major Bleeding ◽

Cox Regression ◽

Cohort Analysis ◽

Bleeding Risk ◽

Nonvalvular Atrial Fibrillation ◽

Thrombotic Risk ◽

Hazard Ratios

African Americans (AAs) and obese individuals have increased thrombotic risk. This study evaluated the effectiveness and safety of rivaroxaban versus warfarin in obese, AAs with nonvalvular atrial fibrillation (NVAF) or venous thromboembolism (VTE). Optum® De-Identified Electronic Health Record (EHR) data was used to perform separate propensity-score matched analyses of adult, oral anticoagulant (OAC)-naïve AAs with NVAF or acute VTE, respectively; who had a body mass index≥30kg/m2 and ≥12-months EHR activity with ≥1-encounter before OAC initiation. Cox regression was performed and reported as hazard ratios (HRs) with 95% confidence intervals (CIs). For the NVAF analysis, 1,969 rivaroxaban- and 1,969 warfarin-users were matched. Rivaroxaban was not associated with a difference in stroke/systemic embolism versus warfarin (HR = 0.88, 95%CI = 0.60-1.28), but less major bleeding (HR = 0.68, 95%CI = 0.50-0.94) was observed. Among 683 rivaroxaban-users with VTE, 1:1 matched to warfarin-users, rivaroxaban did not alter recurrent VTE (HR = 1.36, 95%CI = 0.79-2.34) or major bleeding (HR = 0.80, 95%CI = 0.37-1.71) risk versus warfarin at 6-months (similar findings observed at 3- and 12-months). Rivaroxaban appeared to be associated with similar thrombotic, and similar or lower major bleeding risk versus warfarin in these obese, AA cohorts.

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