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(Stroke. 1996;27:588-592.)
© 1996 American Heart Association, Inc.
Articles |
Aspirin Dose in Stroke Prevention
Beautiful Hypotheses Slain by Ugly Facts
From the John P. Robarts Research Institute, London, Ontario (H.J.M.B., H.M.), and the Department of Epidemiology and Biostatistics, University of Western Ontario (Canada) (M.E.); and the Department of Neurology, Helsinki (Finland) University Hospital (M.K.).
Correspondence to H.J.M. Barnett, MD, The John P. Robarts Research Institute, PO Box 5015, 100 Perth Dr, London, Ontario, Canada N6A 5K8.
Key Words: aspirin • platelet aggregation • stroke prevention
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Introduction |
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Thomas Huxley wrote: "The great tragedy of Science—the slaying of a beautiful hypothesis by an ugly fact."1 Acceptance of several hypotheses has convinced many clinicians to use low-dose aspirin whenever thrombosis or thromboembolism arising in any critical arterial systems threatens vital organs. Two current communications support this concept.2 3 This editorial reflects upon the possibility that this insistence on low dose is not based on unassailable data and could have tragic consequences for stroke prevention.
In the 1950s, the role of platelet-fibrin emboli was identified in patients with transient ocular and cerebral ischemic events.4 In 1965 and 1967 two drugs, sulfinpyrazone and aspirin, were observed to alter functions of blood platelets.5 6 Harrison et al7 reported on two patients whose attacks of frequent amaurosis fugax stopped with administration of 600 mg aspirin. Within 2 to 4 days the attacks would recur when the aspirin was replaced by either placebo or 150 mg dypyridamole. The mechanisms of action of aspirin on platelets or endothelial cells were not elucidated when the Canadian Cooperative Study group launched the first randomized trial using aspirin in thrombosis prevention. We selected an arbitrary dose of aspirin based on the dosage commonly used in pain relief and convenient to put in capsule form. The sulfinpyrazone dose used was the same as that for antigout therapy. The study design was double-blind 2x2 factorial; look-alike capsules of 325 mg aspirin, 200 mg sulfinpyrazone, both, or placebo were given four times daily.8
Subsequent trials were launched involving patients with TIA and
nondisabling
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