Exclusion criteria included rheumatic heart disease, major nontraumatic hemorrhage in the past 5 years, intracranial hemorrhage, endoscopically proven peptic ulcer disease in the past year, esophageal varices, allergy to either study drug, terminal illness, surgery in past 3 months, blood pressure greater than 180/110 mm Hg, or if the primary physician judged that a patient should either be on warfarin or not, based on risk factors.
Patient characteristics. The patients were recruited from 260 general practices in England and Wales. At baseline, 39% to 40% of the patients were already taking warfarin, 12% to 13% had had a prior stroke, 53% to 55% had hypertension, 13% to 14% had diabetes, 19% to 20% had heart failure, and 10% to 12% had a history of myocardial infarction. Patients were followed for an average of 2.7 years.
Aspirin and warfarin regimens. Patients were assigned to either aspirin at a dose of 75 mg/day or warfarin with a target international normalized ratio (INR) of 2.5 and an acceptable range of 2 to 3. Because the study aimed to reflect a realistic primary care setting, the frequency and method of INR testing was left to the discretion of participating physicians.
Patients who had been taking aspirin or warfarin prior to the study discontinued that medicine if they were assigned to the other treatment. Sixty-seven percent of the patients assigned to warfarin continued this treatment throughout the study, and 78% of those who either stopped taking warfarin or never started it were put on either aspirin or clopidogrel. Seventy-six percent of the patients assigned to aspirin took the medicine for the entire study period, while 70% of those who stopped taking aspirin or never started it were either switched to or stayed on warfarin.
INR values. Patients on warfarin had INR values between 2.0 and 3.0 for 67% of the time, below range for 19%, of the time, and above range for 14% of the time. Twenty-two percent of practices had all components of INR monitoring done at the hospital (phlebotomy, INR analysis, and warfarin dosing), 19% of the practices completed all 3 components on site, and the remaining practices had various combinations of onsite and hospital monitoring.
The primary outcomes included disabling stroke (ischemic or hemorrhagic) or clinically significant arterial embolism. There were 24 primary events (1.8% per year) in patients assigned to warfarin compared with 48 primary events (3.8% per year) in those assigned to aspirin, with a relative risk of 0.48 (95% confidence interval [CI], 0.28–0.80 (TABLE). The number needed to treat for 1 year to prevent 1 primary event was 50, when warfarin was compared to aspirin. Warfarin was superior to aspirin in all subgroup analyses, including patients over 85 years old.
Secondary outcomes. There were no significant differences between the warfarin and aspirin groups in the secondary outcomes: hospital admission or death as a result of a non-stroke vascular event (6.1% risk per year with warfarin vs 6.3% risk per year with aspirin), all-cause mortality (8.0% vs 8.4%), and major extracranial hemorrhage (1.4% vs 1.6%). Patients assigned to warfarin, including the subgroup of patients older than 85, did not have an increased risk of a major hemorrhage when compared with those assigned to aspirin (1.9% risk per year with warfarin vs 2.0% risk per year with aspirin; relative risk=0.96; 95% CI, 0.53–1.75).1
TABLE
BAFTA study: Warfarin was as safe as aspirin and more effective in preventing stroke in the elderly
| WARFARIN (488 patients) | ASPIRIN (485 patients) | ||||
|---|---|---|---|---|---|
| PRIMARY EVENTS | Total events | Risk per year | Total events | Risk per year | WARFARIN VA ASPIRIN |
| Stroke | 21 | 1.6% | 44 | 3.4% | RR=0.46 (95% CI, 0.26–0.79) P=.003 |
| Stroke, other intracranial hemorrhage, or systemic embolism | 24 | 1.8% | 48 | 3.8% | RR=0.48 (95% CI, 0.28–0.80) P=.003 |
| RR, relative risk; CI, confidence interval. | |||||
| Source: Mant J, Hobbs FD, Fletcher K et al. 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. Lancet 2007;370:493-503. | |||||
What’s new?: Age alone does not preclude warfarin
The key finding from the BAFTA study is that advanced age alone is not a contraindication to the use of warfarin for stroke prevention in elderly patients with atrial fibrillation.
This is the first randomized controlled trial of warfarin for atrial fibrillation that included only patients ages 75 and older, conducted in a primary care setting.5
Limitations of earlier studies. The most recent meta-analysis of antithrombotic therapy for stroke prevention in patients with atrial fibrillation included 29 trials with 28,044 patients. This analysis concluded that although both warfarin and aspirin are effective in reducing the risk of stroke in patients with atrial fibrillation (warfarin by 60% and aspirin by 20%), warfarin was more effective than aspirin (relative risk reduction of 39%), with very small (≤0.3% per year) absolute increases in major extracranial hemorrhage.
The average age of patients in those trials, however, was 71. The authors identified the lack of data on older patients (who are at higher risk for serious bleeding events) as a limitation of the meta-analysis. Many of these trials took place in settings with closer monitoring of INR and warfarin dosing than is customary in a primary care setting.5
