Relation of the HAS-BLED bleeding risk score to major bleeding, cardiovascular events, and mortality in anticoagulated patients with atrial fibrillation.

Gallego P ，Roldán V ，Torregrosa JM ，Gálvez J ，Valdés M ，Vicente V ，Marín F ，Lip GY ... -  《-》

Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drug

The purpose of this study was to investigate predictors of bleeding in a cohort of anticoagulated patients and to evaluate the predictive value of several bleeding risk stratification schemas. The risk of bleeding during antithrombotic therapy in patients with atrial fibrillation (AF) is not homogeneous, and several clinical risk factors have been incorporated into clinical bleeding risk stratification schemas. Current risk stratification schemas for bleeding during anticoagulation therapy have been based on complex scoring systems that are difficult to apply in clinical practice, and few have been derived and validated in AF cohorts. We investigated predictors of bleeding in a cohort of 7,329 patients with AF participating in the SPORTIF (Stroke Prevention Using an ORal Thrombin Inhibitor in Atrial Fibrillation) III and V clinical trials and evaluated the predictive value of several risk stratification schemas by multivariate analysis. Patients were anticoagulated orally with either adjusted-dose warfarin (target international normalized ratio 2 to 3) or fixed-dose ximelagatran 36 mg twice daily. Major bleeding was centrally adjudicated, and concurrent aspirin therapy was allowed in patients with clinical atherosclerosis. By multivariate analyses, significant predictors of bleeding were concurrent aspirin use (hazard ratio [HR]: 2.10; 95% confidence interval [CI]: 1.59 to 2.77; p < 0.001); renal impairment (HR: 1.98; 95% CI: 1.42 to 2.76; p < 0.001); age 75 years or older (HR: 1.63; 95% CI: 1.23 to 2.17; p = 0.0008); diabetes (HR: 1.47; 95% CI: 1.10 to 1.97; p = 0.009), and heart failure or left ventricular dysfunction (HR: 1.32; 95% CI: 1.01 to 1.73; p = 0.041). Of the tested schemas, the new HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score performed best, with a stepwise increase in rates of major bleeding with increasing HAS-BLED score (p(trend) <0.0001). The c statistic for bleeding varied between 0.50 and 0.67 in the overall entire cohort and 0.68 among patients naive to warfarin at baseline (n = 769). This analysis identifies diabetes and heart failure or left ventricular dysfunction as potential risk factors for bleeding in AF beyond those previously recognized. Of the contemporary bleeding risk stratification schemas, the new HAS-BLED scheme offers useful predictive capacity for bleeding over previously published schemas and may be simpler to apply.

Lip GY ，Frison L ，Halperin JL ，Lane DA ... -  《-》

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 ... -  《-》

Should we recommend oral anticoagulation therapy in patients with atrial fibrillation undergoing coronary artery stenting with a high HAS-BLED bleeding risk score?

Ruiz-Nodar JM ，Marín F ，Roldán V ，Valencia J ，Manzano-Fernández S ，Caballero L ，Hurtado JA ，Sogorb F ，Valdés M ，Lip GY ... -  《-》

Predictive value of the CHA2DS2-VASc score in atrial fibrillation patients at high risk for stroke despite oral anticoagulation.

The risk of stroke in atrial fibrillation is heterogeneous and depends upon underlying clinical conditions included in current risk stratification schemes. Recently, the CHA(2)DS(2)-VASc score has been included in guidelines to be more inclusive of common stroke risk factors seen in everyday clinical practice, and useful in defining "truly low risk" subjects. We aimed to assess the usefulness of CHA(2)DS(2)-VASc score to give us an additional prognostic perspective for adverse events and mortality among "real world" anticoagulated patients with atrial fibrillation who are often elderly with many comorbidities. Consecutive outpatients with permanent/paroxysmal nonvalvular atrial fibrillation with CHA(2)DS(2)-VASc≥2 and stabilized oral anticoagulation (international normalized ratio 2.0-3.0) for at least the preceding 6 months were recruited. Patients with CHA(2)DS(2)-VASc≥2 were selected. Adverse cardiovascular events including stroke, acute coronary syndrome, or heart failure; major bleeds; and mortality were recorded during more than 2.5-year-follow-up. Of 933 patients (93.5%) assessed, 432 were males, median age 76 (71-81) years. After a follow-up of 946 (782-1068) days, 109 patients (11.7%) had adverse cardiovascular events, 80 patients (8.6%) had major bleeds, 101 patients (10.8%) died, and 230 (24.6%) had major adverse events (composite end-point). Increasing CHA(2)DS(2)-VASc score by 1 point had a significant impact on the occurrence of cardiovascular events (hazard ratio=1.27; 95% confidence interval, 1.13-1.44; P<.001), mortality (hazard ratio=1.36; 95% confidence interval, 1.19-1.54; P<.001); and major adverse events (hazard ratio=1.23; 95% confidence interval, 1.13-1.34; P<.001). CHA(2)DS(2)-VASc score was not associated with major bleeding episodes. Among high risk atrial fibrillation patients on oral anticoagulation, CHA(2)DS(2)-VASc successfully predicts cardiovascular events and mortality, but not major bleeds.

Jover E ，Roldán V ，Gallego P ，Hernández-Romero D ，Valdés M ，Vicente V ，Lip GY ，Marín F ... -  《-》