Clinical Research
Heart Rhythm Disorder
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, Drugs/Alcohol Concomitantly) Score

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Objectives

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.

Background

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.

Methods

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.

Results

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 (ptrend <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).

Conclusions

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.

Key Words

anticoagulation
atrial fibrillation
bleeding risk stratification
risk factors

Abbreviations and Acronyms

AF
atrial fibrillation
CI
confidence interval
HR
hazard ratio
INR
international normalized ratio
LV
left ventricular
OAC
oral anticoagulation

Cited by (0)

The SPORTIF III and V studies were sponsored by AstraZeneca. Dr. Lip has received funding for research, educational symposia, consultancy, and lecturing from different manufacturers of drugs used for the treatment of atrial fibrillation and thrombosis, including AstraZeneca, Boehringer, Nayer, Pfizer/BMS, Biotronic, Astellas, Sanofi, Cardiome, and Merck; and is a clinical advisor to the UK NICE Guidelines on AF management, and a task force member of the 2010 ESC guidelines and ACCP9 writing committee. Dr. Frison is an employee of AstraZeneca. Dr. Halperin has received consulting fees from several pharmaceutical manufacturers involved in the development of novel oral anticoagulants for the prevention of thromboembolism in patients with atrial fibrillation, including AstraZeneca, the sponsor of the SPORTIF trials. Dr. Lane has received an investigator-initiated educational grant from Bayer Healthcare, and has received sponsorship to attend meetings from AstraZeneca.