Clinical Practice The risks and benefits of antithrombotic therapy in chronic atrial fibrillation Graeme J Hankey and Natalie J Gray As the risks of adverse effects of warfarin and aspirin in certain patients with chronic atrial fibrillation are high, intervention with these agents should be targeted towards those who will derive most benefit. Clearer guidelines are emerging to identify those patients and to standardise current prescribing practices. (MJA 1996; 164: 624-626) C hronic atrial fibrillation (AF) is a common arrhyth- mia. Its prevalence increases with age, from about 2% in the general population to 5% in people over 60 years and 10% in people over 75 years.t- This arrhythmia is important because it may signify underlying heart disease, may cause symptoms of decreased cardiac output, and is associated with an increased risk of stroke and systemic thromboembolism - about 5% (one in twenty) per year. 1 Management of chronic AF has three principal objectives: to identify and treat the underlying cause; to relieve symp- toms by restoring sinus rhythm or controlling the ventricu- lar rate with antiarrhythmic drugs; and to reduce the risk of stroke and systemic thromboembolism with antithrombotic agents. Until recently, the basis for prophylactic management of chronic AF with antithrombotic drugs consisted of the results of uncontrolled, non-randomised studies. The sub- sequent publication of six large randomised, controlled trials has helped to clarify several questions about the overall effi- cacy and risks of warfarin and aspirin for stroke prevention in people with chronic AF. 3-8 Review of recent trials of antithrombotic therapy Warfarin versus control Five large randomised, controlled primary prevention trials in people with chronic non-rheumatic AF showed that warfarin reduced the risk of stroke by about two-thirds, from 5% to 2% per year. 3-7 This means that warfarin will prevent about 30 strokes per 1000 patient-years of treatment at a cost of five to eight serious bleeding episodes (intracranial haem- orrhage or systemic haemorrhage requiring blood transfu- sion) per 1000 patients treated for one year. However, this rate of adverse haemorrhages was achieved in patients who were carefully selected, screened and closely followed; 53% to 93% of eligible patients were not included in the trials because of a risk of bleeding. Quality Improvement Unit, Royal Perth Hospital, Perth, WA. Graeme J Hankey, MRCP(UK), FRACP, Consultant Neurologist and Clinical Coordinator of Quality Improvement. Natalie J Gray, EN, Quality Improvement Officer. No reprints will be available. Correspondence: Dr G J Hankey, Wellington Street, Perth, Western Australia 6001. E-mall: gjhankey@uniwa.uwa.edu.au 624 One secondary prevention trial, the European Atrial Fib- rillation Trial (EAFT), showed that, in people with chronic non-rheumatic AF and symptoms of previous transient ischaemic attack (TIA) or stroke, warfarin reduced the risk of stroke by about two-thirds, from 12% to 4% per year." This means that warfarin will prevent about 80 strokes for every 1000 patient-years. Aspirin versus control Three of the primary prevention trials>?and the EAFT8 have shown that aspirin may prevent up to 20 strokes for every 1000 patient-years of treatment. Warfarin versus aspirin The relative benefits and risks of warfarin and aspirin have been clarified by three trials,3,8,9 all of which showed that the rate of stroke was less in patients taking warfarin. In the EAFT, 8 warfarin was more than twice as effective in pre- venting stroke as aspirin (hazard ratio, 0.4; 95% confidence interval, 0.2-0.6). Who is at a high risk of stroke? Although warfarin and aspirin are effective in reducing stroke in patients with chronic AF, it may not be cost-effective to administer these drugs for a year to 1000 patients to prevent 30 strokes at the expense of five to eight serious bleeding episodes in that time. The challenge is to identify the 30 people with chronic AF likely to suffer a stroke (unless given warfarin or aspirin), the five to eight people likely to have a serious bleed (with these drugs), and the remaining 960 who will not have a stroke whether or not they receive warfarin or aspirin. Multiple regression analyses of the data from the cited trials indicate that an increased risk of stroke in people with chronic AF is associated with increasing age; a history of pre- vious TIA, stroke, hypertension or diabetes mellitus; and echocardiographic evidence of left atrial enlargement and global left ventricular dysfunction. 10-12 These risk factors are additive: for people under 65 years with no other risk factors, the annual risk of stroke is about 1% per year, and with one or more risk factor about 5% per year; for people over 75 MJA Vol 164 20 May 1996