Between a Rock and a Hard Place: How Much Do We Really Know About Anticoagulation in Atrial Fibrillation?
Abstract & Commentary
Synopsis: Although we simply do not yet have enough data comparing antiplatelet treatment to anticoagulation in patients with nonrheumatic atrial fibrillation to draw firm conclusions, the evidence for long-term anticoagulation in this group of patients is weak.
Source: Taylor FC, et al. BMJ. 2001;322:321-326.
This is a meta-analysis of all randomized, controlled trials comparing long-term anticoagulation with antiplatelet treatment in patients with nonrheumatic atrial fibrillation. Taylor and associates found 5 such studies.1-5 In aggregate, they included 3298 patients with follow-up ranging from 12-42 months. There were no significant differences in mortality rates (odds ratio [OR] 0.74, confidence interval [CI] 0.39-1.4 for stroke death and OR 0.86, CI 0.63-1.17 for vascular death). There was a statistically significant difference in nonfatal stroke, favoring anticoagulation (OR 0.68, CI 0.46-0.99). Taylor et al reanalyzed this data, excluding 1 trial with weak methodological design and found a nonstatistical difference of nonfatal stroke (OR 0.75, CI 0.50-1.13). There were more major bleeding events among patients on chronic anticoagulation than those on antiplatelet therapy (OR 1.45, CI 0.93-2.27). Taylor et al conclude that there is "considerable uncertainty about the value of long-term anticoagulation compared with antiplatelet treatment."
Comment by Barbara A. Phillips, MD, MSPH
It is ironic that this paper was published at about the same time that Ariel Loewy, whose research helped to unravel the mechanism of the clotting cascade, died of a stroke.6 This meta-analysis (whose first author, Taylor, is a "systematic review training fellow"), underscores how little we really know about the comparative benefits of an easy, relatively safe, inexpensive treatment and a difficult, risky, expensive treatment. Perhaps one of the most important findings of this paper is that the 5 studies currently available simply do not include enough patients to detect a significant superiority of anticoagulation over antiplatelet treatment (if it exists). Given that finding, the trends toward reduced deaths from strokes and vascular events, and the reduced risk of nonfatal stroke with anticoagulation compared with antiplatelet therapy, one might consider erring on the side of using long-term anticoagulation. Unfortunately, there is a considerable downside to chronic anticoagulant use, including a 45% increase in risk of major bleeds and an approximate 15-fold increase in cost with universal chronic anticoagulation compared with universal chronic use of aspirin.7 Taylor et al state, "Given the uncertainty over the greater efficacy of anticoagulation, its undoubted hazards, and the consideration of cost effectiveness we would strongly favour antiplatelet drugs in preference to long-term anticoagulation." I am not so sure. Some might consider a nonfatal stroke worse than a fatal stroke. Ultimately, I think that chronic anticoagulation vs. aspirin in patients with nonrheumatic atrial fibrillation is yet another of those things that we simply need to sit down and talk with the patient about. He/she is assuming risk one way or another, and needs to be actively involved in the decision.
References
1. Petersen P, et al. Lancet. 1989;1:175-179.
2. Gollov AL, et al. Arch Intern Med. 1998;158:1513-1521.
3. Stroke Prevention in Atrial Fibrillation Investigators. Lancet. 1994;343:687-691.
4. Morocutti C, et al. Stroke. 1997;28:1015-1021.
5. Hellemons BS, et al. BMJ. 1999;319:958-964.
6. Nagourney E. Ariel G Loewy, 75, expert on biology of blood clotting. New York Times. March 2, 2001;C14.
7. Gustafsson C, et al. BMJ. 1992;305:1457-1460.
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