Assessing Bleeding Risk in Atrial Fibrillation Patients: Comparing a Bleeding Risk Score Based Only on Modifiable Bleeding Risk Factors against the HAS-BLED Score. The AMADEUS Trial

Abstract

Background The HAS-BLED (hypertension, abnormal renal/liver function, previous stroke, bleeding history or predisposition, labile international normalized ratio [INR], elderly and drugs/alcohol consumption) score has been validated in several scenarios but the recent European guidelines does not recommend any clinical score to assess bleeding risk in atrial fibrillation (AF) patients and only focus on modifiable clinical factors.

Purpose The aim of this study was to test the hypothesis that the HAS-BLED score would perform at least similarly to an approach only based on modifiable bleeding risk factors (i.e. a ‘modifiable bleeding risk factors score’) for predicting bleeding events.

Methods We performed a comparison between the HAS-BLED score and the new ‘modifiable bleeding risk factors score’ in a post hoc analysis in 4,576 patients included in the AMADEUS trial.

Results After 347 (interquartile range, 186–457) days of follow-up, 597 patients (13.0%) experienced any clinically relevant bleeding event and 113 (2.5%) had a major bleeding. Only the HAS-BLED score was significantly associated with the risk of any clinically relevant bleeding (Cox's analysis for HAS-BLED ≥ 3: hazard ratio 1.38; 95% confidence interval [CI], 1.10–1.72; p = 0.005). The ‘modifiable bleeding risk factors score’ ≥ 2 were non-significantly associated with any clinical relevant bleeding. The two scores had modest ability in predicting bleeding events. The HAS-BLED score performed best in predicting any clinically relevant bleeding (c-indexes for HAS-BLED, 0.545 [95% CI, 0.530–0.559] vs. the ‘modifiable bleeding risk factors score’, 0.530 [95% CI, 0.515–0.544]; c-index difference 0.015, z-score = 2.063, p = 0.04). The HAS-BLED score with one, two and three modifiable factors performed significantly better than the ‘modifiable bleeding risk factors scores’ with one, two and three modifiable risk factors.

Conclusion When compared with an approach only based on modifiable bleeding risk factors proposed by European Society of Cardiology (ESC) AF guidelines, the HAS-BLED score performed significantly better in predicting any clinically relevant bleeding in this clinical trial cohort. While modifiable bleeding risk factors should be addressed in all AF patients, the use of a formal bleeding risk score (HAS-BLED) has better predictive value for bleeding risks, and would help decision-making in identifying ‘high risk’ patients for scheduling reviews and follow-up.

Keywords

atrial fibrillation - guideline - risk score - haemorrhage - vitamin k antagonist

• References

• 1 Wilson MR, Parakramawansha R, Quinn TJ, Tait RC. Quality and predictors of anticoagulant control with vitamin K antagonist for stroke prevention in atrial fibrillation. Thromb Haemost 2016; 116 (03) 578-580
• 2 Lip GYH, Lane DA. Bleeding risk assessment in atrial fibrillation: observations on the use and misuse of bleeding risk scores. J Thromb Haemost 2016; 14 (09) 1711-1714
• 3 Roldán V, Marín F. The importance of excellence in the quality of anticoagulation control whilst taking vitamin K antagonists. Thromb Haemost 2015; 113 (04) 671-673
• 4 Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJGM, Lip GYH. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 2010; 138 (05) 1093-1100
• 5 Proietti M, Senoo K, Lane DA, Lip GYH. Major bleeding in patients with non-valvular atrial fibrillation: impact of time in therapeutic range on contemporary bleeding risk scores. Sci Rep 2016; 6: 24376
• 6 Senoo K, Proietti M, Lane DA, Lip GYH. Evaluation of the HAS-BLED, ATRIA, and ORBIT bleeding risk scores in patients with atrial fibrillation taking warfarin. Am J Med 2016; 129 (06) 600-607
• 7 Apostolakis S, Lane DA, Guo Y, Buller H, Lip GYH. 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 atrial fibrillation) study. J Am Coll Cardiol 2012; 60 (09) 861-867
• 8 Kirchhof P, Benussi S, Kotecha D. , et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016; 37 (38) 2893-2962
• 9 Amadeus Investigators, Bousser MG, Bouthier J, Büller HR. , et al. Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial. Lancet 2008; 371: 315-321
• 10 Schulman S, Kearon C. ; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3 (04) 692-694
• 11 Roldan V, Marín F. Assessment of bleeding risk in acute ill medical patients. An essential part of venous thromboembolism prevention. Thromb Haemost 2016; 116 (03) 403-404
• 12 Sjögren V, Grzymala-Lubanski B, Renlund H. , et al. Safety and efficacy of well managed warfarin. A report from the Swedish quality register Auricula. Thromb Haemost 2015; 113 (06) 1370-1377
• 13 Raparelli V, Proietti M, Cangemi R, Lip GYH, Lane DA, Basili S. Adherence to oral anticoagulant therapy in patients with atrial fibrillation. Focus on non-vitamin K antagonist oral anticoagulants. Thromb Haemost 2017; 117 (02) 209-218
• 14 Lip GYH, Lane DA. Assessing bleeding risk in atrial fibrillation with the HAS-BLED and ORBIT scores: clinical application requires focus on the reversible bleeding risk factors. Eur Heart J 2015; 36 (46) 3265-3267
• 15 Senoo K, Lau YC, Lip GY. Updated NICE guideline: management of atrial fibrillation (2014). Expert Rev Cardiovasc Ther 2014; 12 (09) 1037-1040