BAFTA
(2007)Objective
Compare warfarin (INR 2–3) vs aspirin 75 mg/day for prevention of fatal/disabling stroke, intracranial haemorrhage, or clinically significant arterial embolism in primary-care patients aged ≥75 with atrial fibrillation.
Study Summary
• All-stroke rate (secondary): 2.5%/yr on warfarin vs 4.9%/yr on aspirin (RR 0.52, 95% CI 0.33–0.80, p=0.002).
• No excess bleeding on warfarin: extracranial haemorrhage 1.4% vs 1.6%/yr (RR 0.87, 95% CI 0.43–1.73) and all major haemorrhage 1.9% vs 2.0%/yr (RR 0.96, 0.53–1.75).
• All-cause mortality did not differ (8.0% vs 8.4%/yr, RR 0.95, 0.72–1.26); benefit was consistent across age (including ≥85), sex, and CHADS2 subgroups.
Intervention
Warfarin (target INR 2.5, range 2–3) vs aspirin 75 mg once daily
Inclusion Criteria
Age ≥75 years with atrial fibrillation or atrial flutter (documented by study ECG or ECG in prior 2 years); recruited from UK primary care; clinical equipoise between warfarin and aspirin.
Study Design
Arms: Warfarin (INR 2–3) vs aspirin 75 mg/day
Patients per Arm: Warfarin 488, Aspirin 485 (total 973)
Outcome
• All strokes: 2.5% vs 4.9%/yr (RR 0.52, 0.33–0.80, p=0.002); ischaemic stroke 0.8% vs 2.5% (RR 0.30, 0.13–0.63, p=0.0004); haemorrhagic stroke 0.5% vs 0.4% (RR 1.15, 0.29–4.77).
• Extracranial haemorrhage 1.4% vs 1.6%/yr (RR 0.87, 0.43–1.73); all major haemorrhage 1.9% vs 2.0%/yr (RR 0.96, 0.53–1.75).
• All-cause mortality 8.0% vs 8.4%/yr (RR 0.95, 0.72–1.26).
Clinical Question
In community-dwelling patients aged ≥75 with atrial fibrillation, does warfarin (target INR 2–3) reduce fatal or disabling stroke, intracranial haemorrhage, and arterial embolism compared with aspirin 75 mg/day, without an unacceptable increase in major bleeding?
Bottom Line
In primary-care patients ≥75 years with AF, warfarin (INR 2–3) halved the risk of fatal/disabling stroke, intracranial haemorrhage, or arterial embolism versus aspirin 75 mg (1.8% vs 3.8%/yr; RR 0.48) with no meaningful excess in major bleeding.
Major Points
- Warfarin reduced the primary composite endpoint by 52% versus aspirin (RR 0.48, 95% CI 0.28–0.80, p=0.003); absolute risk reduction 2%/yr, NNT 50/yr.
- The benefit was driven predominantly by ischaemic stroke prevention (0.8%/yr on warfarin vs 2.5%/yr on aspirin; RR 0.30, p=0.0004).
- There was no significant increase in extracranial (1.4% vs 1.6%/yr) or total major haemorrhage (1.9% vs 2.0%/yr) with warfarin—including in patients ≥85 years old—when INR was managed to a target of 2.5.
- Efficacy was consistent across prespecified subgroups: age, sex, previous stroke/TIA, method of AF identification, prior warfarin use, and CHADS2 score.
- BAFTA established that age ≥75 alone should not be a contraindication to oral anticoagulation for AF; findings were incorporated into subsequent international guidelines.
Study Design
- Study Type
- Prospective randomised open-label trial with blinded endpoint assessment (PROBE)
- Randomization
- Yes
- Blinding
- Open-label with blinded endpoint adjudication (independent neurologists and geriatrician)
- Sample Size
- 973
- Follow-up
- Mean 2.7 years (SD 1.2); follow-up through September 2006
- Centers
- 260
- Countries
- United Kingdom
Primary Outcome
Definition: First fatal or non-fatal disabling stroke (ischaemic or haemorrhagic), other intracranial haemorrhage, or clinically significant arterial embolism (ITT)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 48 events (3.8%/year) on aspirin | 24 events (1.8%/year) on warfarin | - (0.28–0.80) | 0.003 |
Limitations & Criticisms
- Open-label design (blinded endpoint adjudication mitigates but does not eliminate ascertainment bias).
- Only 21% of eligible identified patients with AF entered the trial (most exclusions reflected clinician preference for one therapy), limiting external generalisability at the high-risk extreme.
- Under-powered for secondary outcomes and safety comparisons: 95% CIs around major haemorrhage remain wide, so a modest bleeding excess with warfarin cannot be excluded.
- Substantial treatment crossover (33% off warfarin; 17% of aspirin group ultimately on warfarin) likely diluted true between-group differences in both efficacy and bleeding.
- Primary endpoint restricted to fatal/disabling stroke—minor strokes and TIAs were not captured as primary events.
- Predates direct oral anticoagulants (DOACs); results inform vitamin K antagonist strategy but should be interpreted alongside subsequent AF DOAC trials in the elderly.
- Aspirin dose fixed at 75 mg (standard UK practice); higher aspirin doses could plausibly have produced more bleeding but not more efficacy.
- INR management reflected routine UK practice (TTR 67%); benefit could differ in settings with poorer or better anticoagulation control.
Citation
Lancet 2007;370(9586):493–503. DOI: 10.1016/S0140-6736(07)61233-1