Comparison of the CHADS2, CHA2DS2-VASc and HAS-BLED scores for the prediction of clinically relevant bleeding in anticoagulated patients with atrial fibrillation: the AMADEUS trial.

Apostolakis S ，Lane DA ，Buller H ，Lip GY ... -  《-》

The HAS-BLED score has better prediction accuracy for major bleeding than CHADS2 or CHA2DS2-VASc scores in anticoagulated patients with atrial fibrillation.

The aim of this study was to test the hypothesis that a specific bleeding risk score, HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly), was better at predicting major bleeding compared with CHADS2 (congestive heart failure, hypertension, 75 years of age or older, diabetes mellitus, and previous stroke or transient ischemic attack) and CHA2DS2-VASc (congestive heart failure, hypertension, 75 years of age and older, diabetes mellitus, previous stroke or transient ischemic attack, vascular disease, 65 to 74 years of age, female) in anticoagulated atrial fibrillation (AF) patients. The CHADS2 and CHA2DS2-VASc scores are well-validated stroke risk prediction scores for AF, but are also associated with increased bleeding and mortality. We recruited 1,370 consecutive AF patients (49% male; median age, 76 years) receiving oral anticoagulation therapy from our outpatient anticoagulation clinic, all of whom were receiving acenocoumarol and had an international normalized ratio between 2.0 and 3.0 during the preceding 6 months. During follow-up, major bleeding events were identified by the 2005 International Society on Thrombosis and Haemostasis criteria. Model performance was evaluated by calculating the C-statistic, and the improvement in predictive accuracy was evaluated by calculating the net reclassification improvement and integrated discrimination improvement. After a median follow-up of 996 (range, 802 to 1,254) days, 114 patients (3.0%/year) presented with a major bleeding event; 31 of these events were intracranial hemorrhages (0.8%/year). Based on the C-statistic, HAS-BLED had a model performance superior to that of both CHADS2 and CHA2DS2-VASc (both p < 0.001). Both net reclassification improvement and integrated discrimination improvement analyses also show that HAS-BLED was more accurately associated with major bleeding compared with CHADS2 and CHA2DS2-VASc scores. In anticoagulated AF patients, a validated specific bleeding risk score, HAS-BLED, should be used for assessing major bleeding. The practice of using CHADS2 and CHA2DS2-VASc as a measure of high bleeding risk should be discouraged, given its inferior predictive performance compared with the HAS-BLED score.

Roldán V ，Marín F ，Manzano-Fernández S ，Gallego P ，Vílchez JA ，Valdés M ，Vicente V ，Lip GY ... -  《-》

The predictive ability of the CHADS2 and CHA2DS2-VASc scores for bleeding risk in atrial fibrillation: the MAQI(2) experience.

Guidelines recommend the assessment of stroke and bleeding risk before initiating warfarin anticoagulation in patients with atrial fibrillation. Many of the elements used to predict stroke also overlap with bleeding risk in atrial fibrillation patients and it is tempting to use stroke risk scores to efficiently estimate bleeding risk. Comparison of stroke risk scores to bleeding risk scores to predict bleeding has not been thoroughly assessed. 2600 patients followed at seven anticoagulation clinics were followed from October 2009-May 2013. Five risk models (CHADS2, CHA2DS2-VASc, HEMORR2HAGES, HAS-BLED and ATRIA) were retrospectively applied to each patient. The primary outcome was the first major bleeding event. Area under the ROC curves were compared with C statistic and net reclassification improvement (NRI) analysis was performed. 110 patients experienced a major bleeding event in 2581.6 patient-years (4.5%/year). Mean follow up was 1.0±0.8years. All of the formal bleeding risk scores had a modest predictive value for first major bleeding events (C statistic 0.66-0.69), performing better than CHADS2 and CHA2DS2-VASc scores (C statistic difference 0.10 - 0.16). NRI analysis demonstrated a 52-69% and 47-64% improvement of the formal bleeding risk scores over the CHADS2 score and CHA2DS2-VASc score, respectively. The CHADS2 and CHA2DS2-VASc scores did not perform as well as formal bleeding risk scores for prediction of major bleeding in non-valvular atrial fibrillation patients treated with warfarin. All three bleeding risk scores (HAS-BLED, ATRIA and HEMORR2HAGES) performed moderately well.

Barnes GD ，Gu X ，Haymart B ，Kline-Rogers E ，Almany S ，Kozlowski J ，Besley D ，Krol GD ，Froehlich JB ，Kaatz S ... -  《-》

Performance of the HEMORR(2)HAGES, ATRIA, and HAS-BLED bleeding risk-prediction scores in patients with atrial fibrillation undergoing anticoagulation: the AMADEUS (evaluating the use of SR34006 compared to warfarin or acenocoumarol in patients with atria

The objective of this study was to compare the predictive performance of bleeding risk-estimation tools in a cohort of patients with atrial fibrillation (AF) undergoing anticoagulation. Three bleeding risk-prediction schemes have been derived for and validated in patients with AF: HEMORR(2)HAGES (Hepatic or Renal Disease, Ethanol Abuse, Malignancy, Older Age, Reduced Platelet Count or Function, Re-Bleeding, Hypertension, Anemia, Genetic Factors, Excessive Fall Risk and Stroke), ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation), and HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile International Normalized Ratio, Elderly, Drugs/Alcohol). Τhe relative predictive values of these bleeding scores have not previously been compared. We analyzed the dataset from the AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation) trial, a multicenter, randomized, open-label noninferiority study that compared fixed-dose idraparinux with adjustable-dose oral vitamin K antagonist therapy in patients with AF. The principal safety outcome was any clinically relevant bleeding event, which was a composite of major bleeding plus clinically relevant nonmajor bleeding. The HAS-BLED score performed best in predicting any clinically relevant bleeding, reflected both in net reclassification improvement (10.3% and 13% improvement compared with HEMORR(2)HAGES and ATRIA, respectively) and receiver-operating characteristic (ROC) analyses (c-indexes: 0.60 vs. 0.55 and 0.50 for HAS-BLED vs. HEMORR(2)AGES and ATRIA, respectively). Using decision-curve analysis, the HAS-BLED score demonstrated superior performance compared with ATRIA and HEMORR(2)HAGES at any threshold probability for clinically relevant bleeding. HAS-BLED was the only score that demonstrated a significant predictive performance for intracranial hemorrhage (c-index: 0.75; p = 0.03). An ATRIA score >3 was not significantly associated with the risk for any clinically relevant bleeding on Cox regression or on ROC analysis (c-index: 0.50; p = 0.87). All 3 tested bleeding risk-prediction scores demonstrated only modest performance in predicting any clinically relevant bleeding, although the HAS-BLED score performed better than the HEMORR(2)HAGES and ATRIA scores, as reflected by ROC analysis, reclassification analysis, and decision-curve analysis. Only HAS-BLED demonstrated a significant predictive performance for intracranial hemorrhage. Given its simplicity, the HAS-BLED score may be an attractive method for the estimation of oral anticoagulant-related bleeding risk for use in clinical practice, supporting recommendations in international guidelines.

Apostolakis S ，Lane DA ，Guo Y ，Buller H ，Lip GY ... -  《-》

Stroke and bleeding risk co-distribution in real-world patients with atrial fibrillation: the Euro Heart Survey.

The choice to recommend antithrombotic therapy to patients with atrial fibrillation should rely on cardioembolic and bleeding risk stratification. Sharing some risk factors, schemes to predict thrombotic and bleeding risk are expected not to be independent, yet the degree of their association has never been clearly quantified. We described the cardioembolic (Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack [CHADS2]/Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack, Vascular disease, Age 65-75, Sex category i.e. females [CHA2DS2-VASc]) and bleeding risk (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (>65 years), Drugs/alcohol concomitantly [HAS-BLED]) co-distribution among patients of the Euro Heart Survey on atrial fibrillation. We measured the within-patient correlation (Spearman) and concordance between the 2 types of score and score-based risk categorization (low, intermediate, high). The score-based predicted risk co-classification was then related to the observed 1-year stroke and bleeding occurrence. In 3920 patients, we found a between-scores correlation of 0.416 (P < .001) between HAS-BLED and CHADS2, and 0.512 (P < .001) between HAS-BLED and CHA2DS2-VASc. In 89% (CHADS2/HAS-BLED) and 97% (CHA2DS2-VASc/HAS-BLED) of patients, the bleeding risk category was equal to or lower than their cardioembolic risk category (P < .001 for symmetry test). A complete concordance between risk categories was found in 39.6% (CHADS2/HAS-BLED) and 21.7% (CHA2DS2-VASc/HAS-BLED) of patients; 4.4% (CHADS2/HAS-BLED) and 7.7% (CHA2DS2-VASc/HAS-BLED) of patients had high cardioembolic risk/low bleeding risk or vice versa. A tendency for an increasing frequency of stroke was observed for increasing bleeding risk within cardioembolic risk categories and vice versa. In a real-world population with atrial fibrillation, we confirmed that the cardioembolic and bleeding risk classifications are correlated but not exchangeable. It is then worth verifying the advantages of a strategy adopting a combined risk assessment over a strategy relying only on the cardioembolic risk evaluation.

Marcucci M ，Lip GY ，Nieuwlaat R ，Pisters R ，Crijns HJ ，Iorio A ... -  《-》