Age Should Not Rule Out the Use of Warfarin for Stroke Prevention

BIRMINGHAM, England, Aug. 9 -- Warfarin (Coumadin) is more effective than aspirin for stroke prevention among elderly patients with atrial fibrillation, and it does not seem to increase the risk for major bleeds, according to investigators here.

In a randomized trial of nearly 1,000 patients ages 75 and older with atrial fibrillation, those who took warfarin had a 52% lower risk of an ischemic stroke, hemorrhagic stroke, intracranial hemorrhage or significant arterial embolism than did those who received aspirin.

Moreover, warfarin did not increase the risk of major hemorrhages compared with aspirin, reported Jonathan Mant, M.D., of the University of Birmingham, and colleagues, in the Aug.11 issue of The Lancet.

"These data lend support to the use of anticoagulation for all people aged over 75 years who have atrial fibrillation, unless there are contraindications or the patient decides that the size of the benefit is not worth the inconvenience of the treatment," the authors wrote.

In the Birmingham Atrial Fibrillation Treatment of the Age (BAFTA) study, patients with a mean age of 81.5 were randomized to 75 mg/day of aspirin or to warfarin therapy with a target international normalized ratio (INR) of 2-3.

During approximately 2.7 years of follow-up, there were 24 events in the 488 patients taking warfarin including 21 strokes, two intracranial hemorrhages and one systemic embolus. By contrast, there were 49 events seen in the 485 patients taking daily aspirin including 44 strokes, one intracranial hemorrhage and three systemic emboli.

The yearly risk of stroke was 1.8% among patients taking warfarin, compared with 3.8% among those patients who were taking aspirin therapy to reduce their risk of stroke (P=0.003). The absolute risk reduction of warfarin was only 2% per year because of the low event rates seen in the study (95% CI 0.7-3.2). The number needed to treat for one year to prevent one primary event was 50, the researchers reported.

Although there had been concern that warfarin would increase the risk of major bleeds compared with other treatments in the elderly, the BAFTA study showed that warfarin was no more dangerous than aspirin. There was a 1.9% yearly rate of major hemorrhage including intracranial bleed and hemorrhagic stroke in the warfarin group, compared with a 2.0% yearly rate in the aspirin users (RR 0.96; 95% CI 0.53-1.75).

The yearly risk of major bleed did, however, increase with age in both arms. The yearly risk of extracranial hemorrhage was 1.4% in patients taking warfarin, compared with 1.6% among their counterparts who tool aspirin (RR 0.87; 95% CI 0.43-1.73), The absolute risk reduction for extracranial hemorrhage was 0.2%, the study showed.

In an accompanying editorial, David Garcia, M.D., of the University of New Mexico in Albuquerque, and Elaine Hylek, M.D., of Boston University pointed out that patients could not be included in this trial if warfarin was considered the only effective stroke prevention treatment for them. These patients thus had a lower risk of stroke than those in other studies. The study shows that even in low-risk groups, the benefits of anticoagulation exceed those seen with antiplatelet therapy, they wrote.

"In the future our greatest challenge will be to identify this patients (elderly or not) who are truly at the highest risk of major bleed, particularly intracranial hemorrhage," they added. "For everyone else the benefits of well-managed warfarin substantially outweigh its risks."

The relative contraindications to warfarin use in elderly patients are prior intracranial hemorrhages, in particular cerebral amyloid angiopathy, but also hypertensive bleeds and subdural hematoma and extensive small vessel disease such as periventricular white matter demyelination, commented Derk W. Krieger, M.D. Ph.D., a neurologist at the Cleveland Clinic.

"There is no question that warfarin is better than aspirin, and even aspirin plus clopidogrel (Plavix) for stroke prevention in atrial fibrillation," he said in an interview. "The BAFTA study nicely applies this 'dogma' to the elderly and even though many physicians are wary to prescribe warfarin to the elderly due to fall risk, the risk-benefit analysis is in favor of warfarin."