Elsevier

The Lancet

Volume 370, Issue 9586, 11–17 August 2007, Pages 493-503
The Lancet

Articles
Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial

https://doi.org/10.1016/S0140-6736(07)61233-1Get rights and content

Summary

Background

Anticoagulants are more effective than antiplatelet agents at reducing stroke risk in patients with atrial fibrillation, but whether this benefit outweighs the increased risk of bleeding in elderly patients is unknown. We assessed whether warfarin reduced risk of major stroke, arterial embolism, or other intracranial haemorrhage compared with aspirin in elderly patients.

Methods

973 patients aged 75 years or over (mean age 81·5 years, SD 4·2) with atrial fibrillation were recruited from primary care and randomly assigned to warfarin (target international normalised ratio 2–3) or aspirin (75 mg per day). Follow-up was for a mean of 2·7 years (SD 1·2). The primary endpoint was fatal or disabling stroke (ischaemic or haemorrhagic), intracranial haemorrhage, or clinically significant arterial embolism. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN89345269.

Findings

There were 24 primary events (21 strokes, two other intracranial haemorrhages, and one systemic embolus) in people assigned to warfarin and 48 primary events (44 strokes, one other intracranial haemorrhage, and three systemic emboli) in people assigned to aspirin (yearly risk 1·8% vs 3·8%, relative risk 0·48, 95% CI 0·28–0·80, p=0·003; absolute yearly risk reduction 2%, 95% CI 0·7–3·2). Yearly risk of extracranial haemorrhage was 1·4% (warfarin) versus 1·6% (aspirin) (relative risk 0·87, 0·43–1·73; absolute risk reduction 0·2%, −0·7 to 1·2).

Interpretation

These data support the use of anticoagulation therapy for people aged over 75 who have atrial fibrillation, unless there are contraindications or the patient decides that the benefits are not worth the inconvenience.

Introduction

12% of people aged over 75 years have atrial fibrillation,1 and 56% of people with this arrhythmia are over the age of 75.2 Atrial fibrillation is a major risk factor for stroke, leading to a fivefold increase in risk.3 Because risk of stroke increases with age,4 stroke prevention in elderly people with atrial fibrillation is a key aspect of management for this group.

Anticoagulation therapy with warfarin is highly effective at reducing stroke risk, but is associated with monitoring costs and a higher risk of haemorrhage compared with other treatments.5, 6 Antiplatelet agents such as aspirin provide a more convenient but less effective alternative.7 A meta-analysis of individual-patient data from trials showed that anticoagulants are significantly more effective than aspirin at preventing stroke, but that this benefit is at the cost of higher risk of major bleeding.8 Concerns have been expressed over the applicability of the aforementioned evidence to elderly patients with atrial fibrillation, particularly in primary care settings.9, 10, 11, 12 Older patients were significantly under-represented in the trials: the mean age of participants in trials that compared anticoagulation therapy with no treatment was 69 years,5 and the mean age of participants in trials that compared anticoagulants with antiplatelet agents was 72 years.8 In the large Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W),13 in which treatment with clopidogrel plus aspirin was compared with oral anticoagulation therapy, the mean age of participants was 70 years. This younger age of participants in trials as compared with routine clinical practice is a potential drawback because several studies have shown that risk of serious haemorrhage in patients on anticoagulation increases with age.14, 15, 16, 17 For example, in the Stroke Prevention in Atrial Fibrillation (SPAF) II trial,18 the annual risk of stroke with haemorrhagic or ischaemic residual deficit was slightly higher in the subgroup of patients aged over 75 years assigned to warfarin as opposed to aspirin (4·6% vs 4·3%). In a meta-analysis of data from individual patients aged 75 years or over who were included in trials of aspirin versus anticoagulants, a 2·2% lower risk of ischaemic stroke in those on warfarin was potentially offset by a 1·7% greater risk of a major bleed.8 However, the CIs around risk of stroke and risk of bleed were wide, because few patients aged 75 years or over were included within the trials. In addition, the frequency of anticoagulant-associated intracerebral haemorrhage has risen substantially through the 1990s, particularly in the elderly, raising further concerns about the possible overuse of anticoagulation.19

Evidence from trials of warfarin versus aspirin in primary care populations, which might be at lower risk of stroke than hospital-based populations, is mixed. Although the Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation (AFASAK) study20 reported lower risk of thromboembolism in patients on warfarin than in those on aspirin, Hellemons and colleagues21 and Gullov and colleagues22 in their trials did not show a difference between effects of the treatments; however, these studies21, 22 were underpowered.23

Uncertainty over the optimum treatment of elderly people with atrial fibrillation is evident in current guidelines. Guidelines produced jointly by the American College of Cardiology, the American Heart Association, and the European Society of Cardiology for the management of atrial fibrillation24 recommend use of anticoagulants for patients who have two or more risk factors for stroke (of which age 75 years or over is one), but these guidelines also suggest that patients aged 75 years or older at high risk of bleeding can be treated with a lower international normalised ratio (INR) target than was used in the aforementioned trials.5, 8 Guidelines in England and Wales on the one hand recommend that patients aged 75 years or over with an additional risk factor should be given anticoagulants, but on the other hand recommend that the ages of these patients as a risk factor for haemorrhage should be taken into account.25 This confusion in guidelines reflects practice, and currently less than half of elderly patients receive warfarin.26, 27, 28

In view of these uncertainties and concerns over thromboprophylaxis for elderly people who have atrial fibrillation, the Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) study compared the efficacy of warfarin with that of aspirin for the prevention of stroke in a primary care population of patients aged 75 years or over who have atrial fibrillation.

Section snippets

Study design and participants

BAFTA was a prospective randomised open-label trial with blind assessment of endpoints. The primary aim was to compare the frequency of fatal and non-fatal disabling stroke (ischaemic or haemorrhagic), intracranial haemorrhage, and other clinically significant arterial embolism in patients who had been randomly assigned to warfarin versus aspirin. The methods used for the BAFTA study are reported in detail elsewhere.29 Secondary aims were to compare the frequency of major haemorrhage, other

Results

Figure 1 shows the trial profile. 3231 (70%) of the 4639 patients confirmed to have atrial fibrillation were identified because their primary care records featured atrial fibrillation, and the other 1408 (30%) were identified because they had an irregular pulse in opportunistic screening. Of the whole cohort, 973 (21%) people entered the study. These patients came from 234 of the 260 participating practices; the number of patients recruited per practice ranged from 1 (53 practices) to 21 (1

Discussion

We have shown that warfarin is more effective than aspirin in prevention of stroke in people with atrial fibrillation who are aged 75 or over. With respect to our primary aim, we showed that the frequency of major stroke, arterial embolism, and intracranial haemorrhage was significantly lower in patients on warfarin than in those on aspirin. With respect to our secondary aims, we recorded no evidence that anticoagulants were more hazardous than aspirin therapy in this age-group, although the

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