Does Warfarin Benefit Offset Hemorrhage Risk in Elderly AF Patients?

Abstract & Commentary

By John J. Caronna, MD, Vice-Chairman, Department of Neurology, Cornell University Medical Center, Professor of Clinical Neurology, NewYork-Presbyterian Hospital. Dr. Caronna reports no financial relationship relevant to this field of study.

Synopsis: Elderly patients with atrial fibrillation (AF) benefit from warfarin, with a 50% reduction in stroke risk.

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 randomized controlled trial. Lancet 2007; 370:493-503.

Atrial fibrillation (AF) is a major risk factor for stroke, leading to a five-fold increase in risk.1 More than 10% of individuals older than 75 have AF, and more than 50% of people with AF are older than age 75. Anticoagulation with warfarin is highly effective for stroke prevention in patients with AF. The risk reduction with warfarin treatment is 64%, compared to 22% with aspirin alone as treatment.2

Stroke risk from AF increases with age, but old age is an independent risk factor for warfarin-associated hemorrhage.3 In addition, physicians have concerns about whether the risk-reduction benefit of warfarin in younger patients can be extrapolated to older age groups. Older patients were significantly under-represented in earlier trials; the mean age of participants in trials that compared anticoagulants with antiplatelet agents was 72 years.3

Mant and colleagues have reported the results of the Birmingham (United Kingdom) AF treatment in the aged (BAFTA) study, in which 973 patients age 75 and older (mean age, 81.5 years; SD ± 4.2) with AF were randomized to warfarin (target INR 2-3) or aspirin 75 mg and followed for a mean of 2.7 years (SD ± 1.2). The primary end points were: fatal or disabling stroke (ischemic or hemorrhagic), intracranial hemorrhage, or clinically significant arterial embolism.

Because it would be unethical to deny warfarin to patients in whom it is indicated, participation in BAFTA was restricted to patients for whom there was clinical uncertainty about which of the two treatments should be used. This eligibility requirement probably led to the recruitment of patients at a lower risk of stroke.

There were 24 primary events (21 strokes, two other intracranial hemorrhages, and one systemic embolus) in the warfarin group and 48 primary events (44 strokes, one other intracranial hemorrhage, and three systemic emboli) in the aspirin group. Therefore, warfarin was superior to aspirin in the prevention of stroke (yearly risk 1.8% vs. 3.8%, respectively) and it was no more hazardous than aspirin in terms of major hemorrhage (yearly risk 1.4% vs. 1.6%, respectively). The authors, therefore, concluded that their data support warfarin use for AF patients older than age 75 unless there are contraindications to its use or the patients decide that the benefits are not worth the inconvenience.

Commentary

As noted in an editorial4 that accompanied this report, the fact that the BAFTA study showed that warfarin is more effective than aspirin, even in a relatively low-risk group of patients, adds to other evidence that in AF patients anticoagulation is more effective than antiplatelet therapy. The lack of difference in major hemorrhage between the two groups of elderly patients is surprising. Again, the low rate of warfarin-associated hemorrhage may be due to the overall healthier population studied. In well-managed warfarin treatment, the benefits outweigh the risks in every age group; however, the physician should determine which individual patients have the highest risk of major bleeding (e.g., those who have amyloid angiopathy or are non-compliant). The safety and well being of the individual patient is paramount, and the decision whether to use warfarin in each case is the responsibility of the patient's physician.

References

1. Wolf PA, et al. Stroke 1991; 22:983-988.

2. Hart RG, et al. Ann Intern Med 2007; 146:857-867.

3. Van Walraven C, et al. JAMA 2002; 288:2441-2448.

4. Garcia D, Hylek E. Lancet 2007; 370:460-461.