Prof. Gregory Y. H. Lip
Certain clinical and echocardiographic features are associated with an increase in stroke and thromboembolic risk associated with atrial fibrillation (AF), and may allow risk stratification for thromboprophylaxis and a possible guideline for using antithrombotic therapy in paroxysmal and permanent AF (1) [Table 1].
A recent meta-analysis of these trials showed a relative risk reduction in stroke rate of 68% (95% CI 48% - 72%)(2). A meta-analysis of the major aspirin placebo-controlled trials showed a less dramatic reduction of 22% (95% CI 2% - 38%), which only just reached statistical significance(2). Furthermore, meta-analysis of trials directly comparing warfarin and aspirin showed warfarin reduced the risk of stroke by 36% (95% CI 15% - 52%) relative to aspirin(2). Patients with paroxysmal AF appear to be at the same risk of thromboembolic complications as patients with sustained AF(3).
The immediate risk of thromboembolism, is thought to be minimal if the arrhythmia has been present for less than 48 hours. Thus, in patients presenting de novo with AF, a clear history of arrhythmia onset is necessary in order to guide appropriate antithrombotic therapy and timing of cardioversion. Although no randomised trials have specifically addressed the issue, there is evidence that cardioversion may be safely performed without anticoagulation if the arrhythmia has been present for less than 48 hours.
Cardioversion of AF is known to increase the short-term risk of thromboembolism in the peri-cardioversion period and thus, unless the arrhythmia has been present for less than 48 hours, thromboprophylactic measures are required. The 6th American College of Chest Physicians (ACCP) recommendations for peri-cardioversion anticoagulation are summarised in Table 2. However, by excluding thrombus on transoesophageal echocardiographic (TEE) examination prior to cardioversion, the need for prior anticoagulation could be safely avoided(4). Recent large randomised trials of ‘rate control’ versus ‘rhythm control’ have suggested a trend towards a one-third increase in ischaemic strokes, by a strategy of rhythm control, in view of the high relapse rates to AF post-cardioversion and the early discontinuation of anticoagulation post-cardioversion (5).
The role of antiplatelet agents following acute stroke in sinus rhythm is well proven, but there is less certainty about the potential benefits and hazards of anticoagulant therapy, in patients with AF. One must be sure that there is no ongoing intra-cerebral haemorrhage before commencing anticoagulation.
Before commencing any antithrombotic agent, a CT or MRI scan should be obtained. In AF patients with no evidence of haemorrhage and small infarct size (or no evidence of infarction) warfarin (INR 2-3) can be commenced with minimal risk, provided the patient is normotensive. In AF patients with large areas of cerebral infarction, the initiation of warfarin therapy should be delayed for 2 weeks due to the potential risk of haemorrhagic transformation. The presence of intracranial haemorrhage is an absolute contraindication to the immediate and future use of anticoagulation for stroke prevention in AF.
The recent development of new antiplatelet agents, some of which target different pathways of platelet activation to aspirin, may show promise. The ongoing development of new oral anticoagulants, including factor Xa and thrombin inhibitors, may herald the first true alternatives to warfarin. Indeed, recent data from the SPORTIF-3 trial, presented at American College of Cardiology meeting in March 2003, found that in moderate to high-risk patients with non-valvular paroxysmal or persistent AF, the oral direct thrombin inhibitor, ximelagatran, compared favourably to well-controlled, dose-adjusted warfarin in prevention of stroke and thromboembolism, with lower bleeding risks and without the need for anticoagulation monitoring.
RISK STRATIFICATION AND ANTICOAGULATION IN NONVALVULAR ATRIAL FIBRILLATION
Adapted from Lip 
Assess risk, and reassess regularly:
1. High risk (annual risk of CVA=8-12%)
1.All patients with previous transient ischaemic attack or cerebrovascular accident
2.All patients aged 75 and over with diabetes and/or hypertension
3.All patients with clinical evidence of valve disease, heart failure, thyroid disease, and/or impaired left ventricular function on echocardiography*
2. Moderate risk (annual risk of CVA=4%)
1.All patients aged under 65 with clinical risk factors: diabetes, hypertension, peripheral arterial disease, ischaemic heart disease
2.All patients aged over 65 who are not in high-risk group
3. Low risk (annual risk of CVA=1%)
1.All other patients under 65 with no history of embolism, hypertension, diabetes, or other clinical risk factors.
1.High risk: give warfarin (target INR 2.0-3.0) if no contraindications and possible in practice.
2.Moderate risk: either warfarin or aspirin 75-300 mg. In view of insufficient clear-cut evidence, treatment may be decided on individual cases. Referral and echocardiography may help.
3.Low risk: give aspirin 75-300 mg daily
*Echocardiography-not needed for routine risk assessment but refines clinical risk stratification in case of impaired left ventricular function and valve disease. A large atrium per se is not an independent risk factor on multivariate analysis [CVA = cerebrovascular accident]
RECOMMENDATION FOR ANTICOAGULATION FOR CARDIOVERSION OF PERSISTENT ATRIAL FIBRILLATION
1.for elective cardioversion of AF of > 48 hours duration warfarin (INR 2.0 to 3.0) should be given 3 weeks prior to and continuation of warfarin therapy for 4 weeks after cardioversion;
2.in urgent and emergency cardioversion administration of intravenous heparin followed by warfarin is recommended; and
3.treat atrial flutter similarly
4.no anticoagulation therapy required for SVT or atrial fibrillation of < 48 hours duration.
Based on the 6th ACCP Consensus Conference on Antithrombotic Therapy 
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.
(1) Lip GYH. Thromboprophylaxis for atrial fibrillation. Lancet 1999; 353(9146):4-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10334280&dopt=Abstract
(2) Hart RG, Benavente O, McBride R, Pearce LA. Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis [see comments]. Ann Intern Med 1999; 131(7):492-501. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10507957&dopt=Abstract
(3) Hart RG, Pearce LA, Rothbart RM, McAnulty JH, Asinger RW, Halperin JL. Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke Prevention in Atrial Fibrillation Investigators. J Am Coll Cardiol 2000; 35(1):183-187. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10636278&dopt=Abstract
(4) Fuster V, Ryden LE, Asinger RW, Cannom DS, Crijns HJ, Frye RL, Halperin JL, Kay GN, Klein WW, Levy S, McNamara RL, Prystowsky EN, Wann LS, Wyse DG. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to develop guidelines for the management of patients with atrial fibrillation) developed in collaboration with the North American Society of Pacing and Electrophysiology. Eur Heart J. 2001;22(20):1852-923. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11583910&dopt=Abstract
(5) Verheugt FWA, van GelderI, Wyse G, Hohnloser S, Carlsson J, Crijns H. Paradoxical increase in strokes in the randomized trials on rate versus rhythm control in atrial fibrillation. J Am Coll Cardiol 2003; 41 (Suppl): 130A
Gregory Y.H. LIP, MD FESC Professor of Cardiovascular Medicine Nucleus Member of the Working Group on Hypertension and the Heart. Haemostasis Thrombosis and Vascular Biology Unit University Department of Medicine City Hospital Birmingham B18 7QH England, UK
Tel: +44 121 5075080 Fax: +44 121 554 4083 e-mail: firstname.lastname@example.org www.swbh.nhs.uk/teaching
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