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Improving stroke and thromboembolism risk stratification in chronic atrial fibrillation

An article from the e-journal of the ESC Council for Cardiology Practice

The assessment of stroke risk in atrial fibrillation requires a comprehensive inclusion of risk factors – which can be expressed as the CHA2DS2-VASc score. It will allow identification of ‘truly low risk patients’ where no antithrombotic therapy is an option, whilst all other AF patients with one or more risk factors would be considered for oral anticoagulation, especially with the availability of new oral anticoagulants that overcome the disutility of warfarin.

Atrial Fibrillation

Atrial fibrillation (AF) is the commonest sustained cardiac rhythm disorder, and is encountered in everyday clinical practice.  Irrespective of whether we use a rate-control or rhythm-control strategy, stroke prevention with appropriate thromboprophylaxis still remains central to the management of this common arrhythmia.  When strokes occur in AF patients, the risk of mortality and disability, as well as recurrent stroke is substantially much higher.

Stroke risk in AF is not homogeneous [1].  Various risk factors have been identified largely from non-warfarin arms of clinical trial cohorts, and a few epidemiological/cohort studies [1,2]. Reliance on clinical trial cohort data is problematic, especially since <10% of those screened in the historical trials (those with a placebo or no antithrombotic therapy comparator arm) were ultimately randomized into the intervention.  These risk factors have been used to inform the development of stroke risk stratification schema, which (perhaps artificially) classify AF patients into high, moderate and low risk strata [2], despite stroke risk being a continuous variable.  Various management guidelines have essentially recommended oral anticoagulation (essentially warfarin or other Vitamin K antagonist) is recommended for high risk patients, ‘warfarin or aspirin’ for moderate risk, and aspirin for low risk patients.

Over the last 15 years of so, the various published stroke risk schema only have modest predictive value for thromboembolism, with no improvement in predictive ability over the years [2-4]. Many stroke risk assessment schema classify a large proportion of subjects into the ‘moderate risk’ category where treatment guidelines recommend either warfarin or aspirin, and risk stratification schema that result in classification of a large proportion of AF subjects into the ‘moderate risk’ category could potentially be less useful in everyday clinical practice, since current treatment guidelines recommend the use of either warfarin or aspirin in such patients, causing confusion over which therapy should really be prescribed. Alternatively, classification as ‘moderate risk’ is often used as an excuse not to give anticoagulation, since the guidelines ‘allow’ aspirin.

Given the modest predictive ability for identifying ‘high risk’ subjects and the availability of new oral anticoagulant drugs that overcome the shortcomings of warfarin, stroke risk stratification schema perhaps need to focus more on identifying the ‘truly low risk’ category of patients where no antithrombotic therapy may even be an option, given the increasing debate over the effectiveness of aspirin and potential for harm [5].  This concept was first proposed by van Walraven et al [6] and more recently revisited by Lip and Halperin [4].

Thus, rather than focus on artificial categories of high/moderate/low risk strata, a risk factor based approach is perhaps the best [4]. The CHADS2 schema [Table 1], whilst easy to remember, does not include all potential stroke risk factors, and indeed, ‘clinical heart failure’ (the ‘C’ in CHADS2) is regarded as an inconsistent stroke risk [1].  ‘Major risk factors’ are those with previous stroke or thromboembolism and those age ≥75, whilst ‘clinically relevant non-major risk factors’ are diabetes, hypertension, age 65-74, systolic heart failure (or moderate-severe left ventricular dysfunction), female gender and vascular disease [4,7]. 

These risk factors can be expressed with an acronym, CHA2D2-VASc [Table].  Those patients with one major risk factor or ≥2 ‘clinically relevant non-major’ stroke risk factors (essentially CHA2D2-VASc score of ≥2) should be treated with oral anticoagulation. Those with one ‘clinically relevant non-major’ stroke (ie. CHA2D2-VASc score of 1) can be treated with oral anticoagulation or aspirin, although oral anticoagulation is suggested rather than aspirin, given recent data in such patients [8,9].  Low risk patients (CHA2D2-VASc score=0) are those with no risk factors, and given that such patients are ‘truly low risk’ treatment with aspirin or (preferably) no antithrombotic therapy is appropriate.  

Table 1  - Stroke risk stratification with the CHADS2 and CHA2DS2-VASc scores

 CHADS2 acronym  Score   CHA2DS2-VASc acronym   Score 
 Congestive heart failure    1   Congestive heart failure/LV dysfunction  1
 Hypertension   1   Hypertension   1 
 Aged ≥75 years   1  Aged ≥75 years   2 
 Diabetes mellitus  1  Diabetes mellitus  1
 Stroke/TIA/TE  2  Stroke/TIA/TE  2
Maximum score   Vascular disease (prior MI, PAD, or aortic plaque)  1
     Aged 65-74 years  1
     Sex category (i.e. female gender)  1
    Maximum score   9  


1. Stroke Risk in Atrial Fibrillation Working Group. Independent predictors of stroke in patients with atrial fibrillation: a systematic review. Neurology. 2007;69:546-54.
2. Hughes M, Lip GY; Guideline Development Group, National Clinical Guideline for Management of Atrial Fibrillation in Primary and Secondary Care, National Institute for Health and Clinical Excellence. Stroke and thromboembolism in atrial fibrillation: a systematic review of stroke risk factors, risk stratification schema and cost effectiveness data. Thromb Haemost 2008;99:295-304.
3. Stroke Risk in Atrial Fibrillation Working Group. Comparison of 12 risk stratification schemes to predict stroke in patients with non-valvular atrial fibrillation. Stroke 2008;39:1901-10.
4. Lip GYH, Halperin JL. Improving stroke risk stratification in atrial fibrillation. Am J Med 2010; 123: 483-88
5. Sato H, Ishikawa K, Kitabatake A, Ogawa S, Maruyama Y, Yokota Y, Fukuyama T, Doi Y, Mochizuki S, Izumi T, Takekoshi N, Yoshida K, Hiramori K, Origasa H, Uchiyama S, Matsumoto M, Yamaguchi T, Hori M; Japan Atrial Fibrillation Stroke Trial Group. Low-dose aspirin for prevention of stroke in low-risk patients with atrial fibrillation: Japan Atrial Fibrillation Stroke Trial. Stroke. 2006 Feb;37(2):447-51.
6. van Walraven C, Hart RG, Wells GA, Petersen P, Koudstaal PJ, Gullov AL, Hellemons BS, Koefed BG, Laupacis A. A clinical prediction rule to identify patients with atrial fibrillation and a low risk for stroke while taking aspirin. Arch Intern Med 2003;163:936-43.
7. Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest. 2010 Feb;137(2):263-72.
8. Gorin L, Fauchier L, Nonin E, de Labriolle A, Haguenoer K, Cosnay P, Babuty D, Charbonnier B. Antithrombotic treatment and the risk of death and stroke in patients with atrial fibrillation and a CHADS2 score=1. Thromb Haemost. 2010 Mar 31;103(4):833-40.
9. Lip GY. Anticoagulation therapy and the risk of stroke in patients with atrial fibrillation at 'moderate risk' (CHADS2 score=1): simplifying stroke risk assessment and thromboprophylaxis in real-life clinical practice. Thromb Haemost.2010 Mar 31;103(4):683-5. 


Vol8 N°36

Notes to editor

Gregory YH Lip  MD FRCP Professor of Cardiovascular Medicine
University of Birmingham Centre for Cardiovascular Sciences
City Hospital Birmingham England

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.