It has been estimated that 2.2 million people in the United States and 4.5 million people in the European Union suffer from atrial fibrillation (AF).(1) The prevalence of AF is rapidly increasing as the population ages, with a rate of approximately 8% in individuals older than 80 years of age.(2) Thromboembolism, primarily ischemic stroke, is the most feared and devastating complication of AF.(3-7)
Vitamin K antagonists (VKAs), such as warfarin, have been the standard anticoagulant prescribed for prevention of stroke in patients with AF for over 55 years old. However warfarin has a number of limitations including slow onset of action, multiple food and drug interactions, genetic variability in metabolism, and frequent monitoring of international normalized ratio (INR) due to limited therapeutic index that complicate therapy.(8-12) It is estimated that less than half of warfarin-ligible AF patients are ultimately treated,13-15) and one of the main reasons cited by physicians and patients is the fear of iatrogenic bleeding.(16, 17)
The CHADS2 is a widely used and accepted clinical risk score for evaluating thromboembolic risk in patients with AF.(18) However, for individual patients we must balance the benefit of anticoagulation with the potential risk of serious bleeding. Various clinical factors have been associated with incremental bleeding risk. Numerous bleeding risk assessment strategies have been proposed but complicated scoring systems, varying predictive values and lack of consensus have limited their widespread adoption. We will review three current clinical prediction rules for bleeding in AF that have been developed.
HEMORR2HAGES
HAS-BLED
HAS-BLED was recently included in the European Society of Cardiology guidelines on treatment of patients with AF,(23) as well as the Canadian Cardiovascular Society AF guidelines.(24)
ATRIA
Considerations
All of these scores are easier to use than their predecessors with most risk factors readily available from the medical history or routinely tested in AF patients being evaluated for anticoagulation – this is particularly true for HAS-BLED and ATRIA which contain fewer variables and do not include genetic testing. HAS-BLED has been validated in several cohorts and has begun to be incorporated into national and regional guidelines. It is important to note, however, that HAS-BLED incorporates labile INR, which is a characteristic post-initiation of warfarin. ATRIA performs particularly well in categorizing high risk patients such that a significant proportion of bleeding events occur in that group compared to much smaller percentages in the other scores. A limitation of ATRIA, acknowledged by the developers, is that the database from which score was derived did not contain information on blood pressure or concomitant medications known to increase bleeding risk with warfarin (antiplatelet and nonsteroidal anti-inflammatory medications). ATRIA is also awaiting validation in a second dataset.
Conclusions
These simple clinical prediction scores for bleeding are important tools for accurately assessing the risks and benefits of anticoagulation in patients with AF. With the new factor Xa and IIa inhibitors offering the potential of effective and potentially safer anticoagulation we will likely see a paradigm shift where anticoagulation is recommended to a broader population currently thought to be “low risk” for stroke. These scores will need to be validated and potentially modified for these agents in addition to warfarin. Before widespread adoption of any bleeding prediction rule, further prospective studies need to be performed.
References
- Feinberg WM, Cornell ES, Nightingale SD, et al. Relationship between prothrombin activation fragment F1.2 and international normalized ratio in patients with atrial fibrillation. stroke prevention in atrial fibrillation investigators. Stroke. 1997; 28:1101-1106.
- Furberg CD, Psaty BM, Manolio TA, Gardin JM, Smith VE, Rautaharju PM. Prevalence of atrial fibrillation in elderly subjects (the cardiovascular health study). Am J Cardiol. 1994; 74:236-241.
- Fatkin D, Kelly RP, Feneley MP. Relations between left atrial appendage blood flow velocity, spontaneous echocardiographic contrast and thromboembolic risk in vivo. J Am Coll Cardiol. 1994; 23:961-969.
- Hwang JJ, Ko FN, Li YH, et al. Clinical implications and factors related to left atrial spontaneous echo contrast in chronic nonvalvular atrial fibrillation. Cardiology. 1994; 85:69-75.
- Pop GA, Meeder HJ, Roelandt JR, et al. Transthoracic echo/Doppler in the identification of patients with chronic non-valvular atrial fibrillation at risk for thromboembolic events. Eur Heart J. 1994; 15:1545-1551.
- Conway DS, Pearce LA, Chin BS, Hart RG, Lip GY. Plasma von willebrand factor and soluble p-selectin as indices of endothelial damage and platelet activation in 1321 patients with nonvalvular atrial fibrillation: Relationship to stroke risk factors. Circulation. 2002; 106:1962-1967.
- Conway DS, Pearce LA, Chin BS, Hart RG, Lip GY. Prognostic value of plasma von willebrand factor and soluble P-selectin as indices of endothelial damage and platelet activation in 994 patients with nonvalvular atrial fibrillation. Circulation. 2003; 107:3141-3145.
- Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E. The pharmacology and management of the vitamin K antagonists: The seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest. 2004; 126:204S-233S.
- Turpie AG. New oral anticoagulants in atrial fibrillation. Eur Heart J. 2008; 29:155-165.
- Aithal GP, Day CP, Kesteven PJ, Daly AK. Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet. 1999; 353:717-719.
- D'Andrea G, D'Ambrosio RL, Di Perna P, et al. A polymorphism in the VKORC1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin. Blood. 2005; 105:645-649.
- Marin F, Gonzalez-Conejero R, Capranzano P, Bass TA, Roldan V, Angiolillo DJ. Pharmacogenetics in cardiovascular antithrombotic therapy. J Am Coll Cardiol. 2009; 54:1041-1057.
- Jones M, McEwan P, Morgan CL, Peters JR, Goodfellow J, Currie CJ. Evaluation of the pattern of treatment, level of anticoagulation control, and outcome of treatment with warfarin in patients with non-valvar atrial fibrillation: A record linkage study in a large british population. Heart. 2005; 91:472-477.
- McCormick D, Gurwitz JH, Goldberg RJ, et al. Prevalence and quality of warfarin use for patients with atrial fibrillation in the long-term care setting. Arch Intern Med. 2001; 161:2458-2463.
- Fang MC, Stafford RS, Ruskin JN, Singer DE. National trends in antiarrhythmic and antithrombotic medication use in atrial fibrillation. Arch Intern Med. 2004; 164:55-60.
- Bungard TJ, Ghali WA, McAlister FA, et al. The relative importance of barriers to the prescription of warfarin for nonvalvular atrial fibrillation. Can J Cardiol. 2003; 19:280-284.
- Gross CP, Vogel EW, Dhond AJ, et al. Factors influencing physicians' reported use of anticoagulation therapy in nonvalvular atrial fibrillation: A cross-sectional survey. Clin Ther. 2003; 25:1750-1764.
- Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of clinical classification schemes for predicting stroke: Results from the national registry of atrial fibrillation. JAMA. 2001; 285:2864-2870.
- Gage BF, Yan Y, Milligan PE, et al. Clinical classification schemes for predicting hemorrhage: Results from the national registry of atrial fibrillation (NRAF). Am Heart J. 2006; 151:713-719.
- Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess one-year risk of major bleeding in atrial fibrillation patients: The euro heart survey. Chest. 2010; 138:1093-100.
- Lip GYH, Frison L, Halperin JL, Lane DA. 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. J Am Coll Cardiol. 2011; 57:173-180.
- Olesen JB, Lip GY, Hansen PR, et al. Bleeding risk in 'real world' patients with atrial fibrillation: Comparison of two established bleeding prediction schemes in a nationwide cohort. J Thromb Haemost. 2011; 9:1460-1467.
- European Heart Rhythm Association, European Association for Cardio-Thoracic Surgery, Camm AJ, et al. Guidelines for the management of atrial fibrillation: The task force for the management of atrial fibrillation of the european society of cardiology (ESC). Eur Heart J. 2010; 31:2369-2429.
- Cairns JA, Connolly S, McMurtry S, Stephenson M, Talajic M, CCS Atrial Fibrillation Guidelines Committee. Canadian cardiovascular society atrial fibrillation guidelines 2010: Prevention of stroke and systemic thromboembolism in atrial fibrillation and flutter. Can J Cardiol. 2011; 27:74-90.
- Fang MC, Go AS, Chang Y, et al. A new risk scheme to predict warfarin-associated hemorrhage: The ATRIA (anticoagulation and risk factors in atrial fibrillation) study. J Am Coll Cardiol. 2011; 58:395-401.
Keywords: Atrial Fibrillation, California, Consensus, Denmark, European Union, Factor Xa, Hemorrhage, Hypertension, International Normalized Ratio, Risk Assessment, Stroke, Thromboembolism, United States, Warfarin
< Back to Listings