Abstract/Text: BACKGROUND: Contemporary clinical risk stratification schemata for predicting stroke and thromboembolism (TE) in patients with atrial fibrillation (AF) are largely derived from risk factors identified from trial cohorts. Thus, many potential risk factors have not been included.
METHODS: We refined the 2006 Birmingham/National Institute for Health and Clinical Excellence (NICE) stroke risk stratification schema into a risk factor-based approach by reclassifying and/or incorporating additional new risk factors where relevant. This schema was then compared with existing stroke risk stratification schema in a real-world cohort of patients with AF (n = 1,084) from the Euro Heart Survey for AF.
RESULTS: Risk categorization differed widely between the different schemes compared. Patients classified as high risk ranged from 10.2% with the Framingham schema to 75.7% with the Birmingham 2009 schema. The classic CHADS(2) (Congestive heart failure, Hypertension, Age > 75, Diabetes, prior Stroke/transient ischemic attack) schema categorized the largest proportion (61.9%) into the intermediate-risk strata, whereas the Birmingham 2009 schema classified 15.1% into this category. The Birmingham 2009 schema classified only 9.2% as low risk, whereas the Framingham scheme categorized 48.3% as low risk. Calculated C-statistics suggested modest predictive value of all schema for TE. The Birmingham 2009 schema fared marginally better (C-statistic, 0.606) than CHADS(2). However, those classified as low risk by the Birmingham 2009 and NICE schema were truly low risk with no TE events recorded, whereas TE events occurred in 1.4% of low-risk CHADS(2) subjects. When expressed as a scoring system, the Birmingham 2009 schema (CHA(2)DS(2)-VASc acronym) showed an increase in TE rate with increasing scores (P value for trend = .003).
CONCLUSIONS: Our novel, simple stroke risk stratification schema, based on a risk factor approach, provides some improvement in predictive value for TE over the CHADS(2) schema, with low event rates in low-risk subjects and the classification of only a small proportion of subjects into the intermediate-risk category. This schema could improve our approach to stroke risk stratification in patients with AF.

Abstract/Text: CONTEXT: Patients who have atrial fibrillation (AF) have an increased risk of stroke, but their absolute rate of stroke depends on age and comorbid conditions.
OBJECTIVE: To assess the predictive value of classification schemes that estimate stroke risk in patients with AF.
DESIGN, SETTING, AND PATIENTS: Two existing classification schemes were combined into a new stroke-risk scheme, the CHADS( 2) index, and all 3 classification schemes were validated. The CHADS( 2) was formed by assigning 1 point each for the presence of congestive heart failure, hypertension, age 75 years or older, and diabetes mellitus and by assigning 2 points for history of stroke or transient ischemic attack. Data from peer review organizations representing 7 states were used to assemble a National Registry of AF (NRAF) consisting of 1733 Medicare beneficiaries aged 65 to 95 years who had nonrheumatic AF and were not prescribed warfarin at hospital discharge.
MAIN OUTCOME MEASURE: Hospitalization for ischemic stroke, determined by Medicare claims data.
RESULTS: During 2121 patient-years of follow-up, 94 patients were readmitted to the hospital for ischemic stroke (stroke rate, 4.4 per 100 patient-years). As indicated by a c statistic greater than 0.5, the 2 existing classification schemes predicted stroke better than chance: c of 0.68 (95% confidence interval [CI], 0.65-0.71) for the scheme developed by the Atrial Fibrillation Investigators (AFI) and c of 0.74 (95% CI, 0.71-0.76) for the Stroke Prevention in Atrial Fibrillation (SPAF) III scheme. However, with a c statistic of 0.82 (95% CI, 0.80-0.84), the CHADS( 2) index was the most accurate predictor of stroke. The stroke rate per 100 patient-years without antithrombotic therapy increased by a factor of 1.5 (95% CI, 1.3-1.7) for each 1-point increase in the CHADS( 2) score: 1.9 (95% CI, 1.2-3.0) for a score of 0; 2.8 (95% CI, 2.0-3.8) for 1; 4.0 (95% CI, 3.1-5.1) for 2; 5.9 (95% CI, 4.6-7.3) for 3; 8.5 (95% CI, 6.3-11.1) for 4; 12.5 (95% CI, 8.2-17.5) for 5; and 18.2 (95% CI, 10.5-27.4) for 6.
CONCLUSION: The 2 existing classification schemes and especially a new stroke risk index, CHADS( 2), can quantify risk of stroke for patients who have AF and may aid in selection of antithrombotic therapy.

Abstract/Text: BACKGROUND: Contemporary clinical risk stratification schemata for predicting stroke and thromboembolism (TE) in patients with atrial fibrillation (AF) are largely derived from risk factors identified from trial cohorts. Thus, many potential risk factors have not been included.
METHODS: We refined the 2006 Birmingham/National Institute for Health and Clinical Excellence (NICE) stroke risk stratification schema into a risk factor-based approach by reclassifying and/or incorporating additional new risk factors where relevant. This schema was then compared with existing stroke risk stratification schema in a real-world cohort of patients with AF (n = 1,084) from the Euro Heart Survey for AF.
RESULTS: Risk categorization differed widely between the different schemes compared. Patients classified as high risk ranged from 10.2% with the Framingham schema to 75.7% with the Birmingham 2009 schema. The classic CHADS(2) (Congestive heart failure, Hypertension, Age > 75, Diabetes, prior Stroke/transient ischemic attack) schema categorized the largest proportion (61.9%) into the intermediate-risk strata, whereas the Birmingham 2009 schema classified 15.1% into this category. The Birmingham 2009 schema classified only 9.2% as low risk, whereas the Framingham scheme categorized 48.3% as low risk. Calculated C-statistics suggested modest predictive value of all schema for TE. The Birmingham 2009 schema fared marginally better (C-statistic, 0.606) than CHADS(2). However, those classified as low risk by the Birmingham 2009 and NICE schema were truly low risk with no TE events recorded, whereas TE events occurred in 1.4% of low-risk CHADS(2) subjects. When expressed as a scoring system, the Birmingham 2009 schema (CHA(2)DS(2)-VASc acronym) showed an increase in TE rate with increasing scores (P value for trend = .003).
CONCLUSIONS: Our novel, simple stroke risk stratification schema, based on a risk factor approach, provides some improvement in predictive value for TE over the CHADS(2) schema, with low event rates in low-risk subjects and the classification of only a small proportion of subjects into the intermediate-risk category. This schema could improve our approach to stroke risk stratification in patients with AF.

Abstract/Text: BACKGROUND AND PURPOSE: The risk of stroke in patients with atrial fibrillation (AF) is not homogeneous, and various clinical risk factors have informed the development of stroke risk stratification schemes (RSS). Among anticoagulated cohorts, the emphasis should be on the identification of patients who remain at high risk for stroke despite anticoagulation.
METHODS: We investigated predictors of thromboembolism (TE) risk in an anticoagulated AF clinical trial cohort (n = 7329 subjects) and tested the predictive value of contemporary RSS in this cohort: CHADS₂, Framingham, NICE 2006, American College of Cardiology/American Heart Association/European Society of Cardiology 2006, the 8th American College of Chest Physicians guidelines and the CHA₂DS₂-VASc schemes.
RESULTS: On multivariate analysis, significant predictors of TE were stroke/TIA (hazard ratio [HR], 2.24; P < 0.001), age 75 years or older (HR, 1.77; P = 0.0002), coronary artery disease (HR, 1.52; P = 0.0047), and smoking (HR, 2.10; P = 0.0005), whereas reported alcohol use (HR, 0.70; P = 0.02) was protective. Comparison of contemporary RSS demonstrated variable classification of AF patients into risk strata, although c-statistics for TE were broadly similar among the RSS tested and varied between 0.575 (NICE 2006) and 0.647 (CHA₂DS₂-VASc). CHA₂DS₂-VASc classified 94.2% as being at high risk, whereas most other RSS categorized two-thirds as being at high risk. Of the 184 TE events, 181 (98.4%) occurred in patients identified as being at high risk by the CHA₂DS₂-VASc schema. There was a stepwise increase in TE with increasing CHA₂DS₂-VASc score (P (trend) < 0.0001), which had the highest HR (3.75) among the tested schemes. The negative predictive value (ie, the percent categorized as "not high risk" actually being free from TE) for CHA₂DS₂-VASc was 99.5%.
CONCLUSIONS: Coronary artery disease and smoking are additional risk factors for TE in anticoagulated AF patients, whereas alcohol use appears protective. Of the contemporary stroke RSS, the CHA₂DS₂-VASc scheme correctly identified the greatest proportion of AF patients at high risk, despite the similar predictive ability of most RSS evidenced by the c-statistic.

Abstract/Text: OBJECTIVE: Despite extensive use of oral anticoagulation (OAC) in patients with atrial fibrillation (AF) and the increased bleeding risk associated with such OAC use, no handy quantification tool for assessing this risk exists. We aimed to develop a practical risk score to estimate the 1-year risk for major bleeding (intracranial, hospitalization, hemoglobin decrease > 2 g/L, and/or transfusion) in a cohort of real-world patients with AF.
METHODS: Based on 3,978 patients in the Euro Heart Survey on AF with complete follow-up, all univariate bleeding risk factors in this cohort were used in a multivariate analysis along with historical bleeding risk factors. A new bleeding risk score termed HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (> 65 years), Drugs/alcohol concomitantly) was calculated, incorporating risk factors from the derivation cohort.
RESULTS: Fifty-three (1.5%) major bleeds occurred during 1-year follow-up. The annual bleeding rate increased with increasing risk factors. The predictive accuracy in the overall population using significant risk factors in the derivation cohort (C statistic 0.72) was consistent when applied in several subgroups. Application of the new bleeding risk score (HAS-BLED) gave similar C statistics except where patients were receiving antiplatelet agents alone or no antithrombotic therapy, with C statistics of 0.91 and 0.85, respectively.
CONCLUSION: This simple, novel bleeding risk score (HAS-BLED) provides a practical tool to assess the individual bleeding risk of real-world patients with AF, potentially supporting clinical decision making regarding antithrombotic therapy in patients with AF.

Abstract/Text: OBJECTIVE: Despite extensive use of oral anticoagulation (OAC) in patients with atrial fibrillation (AF) and the increased bleeding risk associated with such OAC use, no handy quantification tool for assessing this risk exists. We aimed to develop a practical risk score to estimate the 1-year risk for major bleeding (intracranial, hospitalization, hemoglobin decrease > 2 g/L, and/or transfusion) in a cohort of real-world patients with AF.
METHODS: Based on 3,978 patients in the Euro Heart Survey on AF with complete follow-up, all univariate bleeding risk factors in this cohort were used in a multivariate analysis along with historical bleeding risk factors. A new bleeding risk score termed HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (> 65 years), Drugs/alcohol concomitantly) was calculated, incorporating risk factors from the derivation cohort.
RESULTS: Fifty-three (1.5%) major bleeds occurred during 1-year follow-up. The annual bleeding rate increased with increasing risk factors. The predictive accuracy in the overall population using significant risk factors in the derivation cohort (C statistic 0.72) was consistent when applied in several subgroups. Application of the new bleeding risk score (HAS-BLED) gave similar C statistics except where patients were receiving antiplatelet agents alone or no antithrombotic therapy, with C statistics of 0.91 and 0.85, respectively.
CONCLUSION: This simple, novel bleeding risk score (HAS-BLED) provides a practical tool to assess the individual bleeding risk of real-world patients with AF, potentially supporting clinical decision making regarding antithrombotic therapy in patients with AF.

Abstract/Text: BACKGROUND: Recently, identification of independent risk factors for ischemic stroke in Japanese non-valvular atrial fibrillation (NVAF) patients was made by analyzing the 5 major Japanese registries: J-RHYTHM Registry, Fushimi AF Registry, Shinken Database, Keio interhospital Cardiovascular Studies, and the Hokuriku-Plus AF Registry.Methods and Results:The predictive value of the risk scheme in Japanese NVAF patients was assessed. Of 16,918 patients, 12,289 NVAF patients were analyzed (mean follow up, 649±181 days). Hazard ratios (HRs) of each significant, independent risk factor were determined by using adjusted Cox-hazard proportional analysis. Scoring system for ischemic stroke was created by transforming HR logarithmically and was estimated by c-statistic. During the 21,820 person-years follow up, 241 ischemic stroke events occurred. Significant risk factors were: being elderly (aged 75-84 years [E], HR=1.74), extreme elderly (≥85 years [EE], HR=2.41), having hypertension (H, HR=1.60), previous stroke (S, HR=2.75), type of AF (persistent/permanent) (T, HR=1.59), and low body mass index <18.5 kg/m2(L, HR=1.55) after adjusting for oral anticoagulant treatment. The score was assigned as follows: 1 point to H, E, L, and T, and 2 points to EE and S (HELT-E2S2score). The C-statistic, using this score, was 0.681 (95% confidence interval [CI]=0.647-0.714), which was significantly higher than those using CHADS2(0.647; 95% CI=0.614-0.681, P=0.027 for comparison) and CHA2DS2-VASc scores (0.641; 95% CI=0.608-0.673, P=0.008).
CONCLUSIONS: The HELT-E2S2score may be useful for identifying Japanese NVAF patients at risk of ischemic stroke.