*The term ‘stroke’ refers to ischemic strokes, those caused by blockage of a blood vessel, while we use the term ‘intracranial hemorrhage’ to indicate bleeding in the brain. The latter condition is often called a stroke as well, however we prefer to separate the two for a more nuanced understanding of harms and benefits.
Source: Aguilar MI, Hart R, Pearce LA. Oral anticoagulants versus antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no history of stroke or transient ischemic attacks. Cochrane Database Syst Rev 2009
Efficacy Endpoints: All strokes (ischemic and hemorrhagic), all disabling or fatal strokes, vascular death, mortality
Harm Endpoints: Intracranial hemorrhage, other major hemorrhage
Narrative: Non-valvular atrial fibrillation (irregular heart beat not caused by a heart valve problem) is the most common cause of strokes due to blood clots traveling from the heart. The overall risk of stroke ranges from 2.5% to 4% per year. Both anti-platelet agents and oral anticoagulants reduce this risk, but both also increase the risk of hemorrhagic stroke and other bleeding.
The review compared anti-platelet agents to anticoagulants in patients with atrial fibrillation but no history of stroke or transient ischemic attack. Eight randomized trials with 9598 subjects were included, with most examining warfarin versus aspirin (75 to 325 mg/day). The target INR range for subjects on warfarin was 2.0 to 3.0. Average follow up was 1.9 years per participant. Warfarin compared to anti-platelet therapies was associated with a modest decrease in ischemic strokes (1.7% less) and also reduced disabling or fatal strokes (0.5%) and vascular death (0.3%). However, warfarin increased the risk of intracranial hemorrhage (0.4%). Overall, warfarin offered only a slight advantage over antiplatelet therapy.
The rate of harms is often inconsistent in randomized trials designed to track benefits, and in the studies included in this review the subjects were carefully selected based on a low risk of bleeding. Moreover, the total number of subjects was small, leaving the studies under-powered for bleeding outcomes. Therefore we have used data from a systematic review of observational studies that suggests the true bleeding rate for patients taking warfarin to be just under 3% for the first 6 months of use, with a 0.6% fatal bleeding rate.[Dahri, Newman] This risk is heavily weighted toward the first 6 months and tapers after, thus we have estimated a total bleeding rate of 4% per year, and 0.6% fatal. After the first year the risks are less well known and poorly documented, therefore we have reported only the first year of hemorrhage rates, and leave all further estimating to physician judgment, as data suggest that this is as accurate as any method for predicting hemorrhage.1
Caveats: Follow up was limited to about 2 years, and it is unclear whether the protective effect of oral anticoagulants extends beyond this period or if the risks of warfarin increase with age, potentially neutralizing these benefits. In addition only 60% of patients achieved the goal INR of 2-3. Similarly, it is unclear whether maintaining this goal would change the results. The aspirin dose was heterogeneous, ranging from 75 to 325 mg/day. Finally, clinicians were not blinded in any of the studies due to obvious difficulty in masking the effects of warfarin and ongoing INR checks. Additionally, in terms of mortality outcomes, the review looked primarily at only vascular mortality, which makes it difficult to know whether or not there is any overall mortality benefit. It seems likely that if there is an overall mortality benefit, therefore, it is negligible.
Note: Remember, these NNTs are when compared to being given aspirin for stroke prevention. For the comparison of warfarin to placebo, please see the Warfarin for Atrial Fibrillation Stroke Prevention NNT summary .
Author: Kirill Shishlov, MD MPH
Published/Updated: October 21, 2013
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