Gathering intelligence on antiplatelet drugs: the view from 30 000 feet: When combined with other information overviews lead to conviction

M Reilly, GA FitzGerald - BMJ, 2002 - bmj.com
M Reilly, GA FitzGerald
BMJ, 2002bmj.com
The efficacy of aspirin in the secondary prevention of myocardial infarction and stroke is
widely accepted. The evidence which supports this perception includes its identification as
an inhibitor of cyclo-oxygenase and platelet aggregation; identification of the major product
of platelet cyclo-oxygenase as thromboxane A2, a vasoconstrictor and platelet agonist; the
discovery that aspirin irreversibly acetylates cyclo-oxygenase, permitting cumulative
inhibition by low doses of thromboxane A2 formation in the presystemic circulation; the …
The efficacy of aspirin in the secondary prevention of myocardial infarction and stroke is widely accepted. The evidence which supports this perception includes its identification as an inhibitor of cyclo-oxygenase and platelet aggregation; identification of the major product of platelet cyclo-oxygenase as thromboxane A2, a vasoconstrictor and platelet agonist; the discovery that aspirin irreversibly acetylates cyclo-oxygenase, permitting cumulative inhibition by low doses of thromboxane A2 formation in the presystemic circulation; the discovery that thromboxane A2 biosynthesis is increased during ischaemic episodes of unstable angina; and the demonstration in individual, controlled, prospective double blind trials that aspirin reduces both myocardial infarction and death in unstable angina by 50%, whether given at 75 mg, 324 mg, or 1300 mg/day. 1 2 Following these discoveries Collins, Peto, Baigent, and their colleagues in Oxford organised the Antithrombotic Trialists’ Collaboration to share data and permit overview analyses of controlled trials of antiplatelet drugs. At the time of the initial reports, these trials mainly involved aspirin and confirmed its efficacy in syndromes of acute vascular occlusion such as unstable angina, while suggesting a net benefit in the secondary prevention of stroke. 3–5 Today, Baigent and colleagues report further analyses (p 71), 6 though a critic of the approach questions whether it has all been worthwhile (p 103). 7
What is the value of overview analyses? Firstly, they serve to summarise the field for the busy practitioner, who has not read in detail the individual trials. A complementary effort is the annual weighting of clinical trials performed by the American College of Chest Physicians. 8 The development of a combined Antithrombotic Trialists’ Collaboration endpoint—nonfatal myocardial infarction, non-fatal stroke, and vascular death—and the visual display of data in a manner that reflects the size of drug effect and the size of the dataset helps spread the word. Remarkably, aspirin continues to be underused in conditions where its efficacy has been well established. A message from the present review is that patients with peripheral vascular disease and those at risk of embolic events may also benefit from aspirin. However, whether such data alone preclude placebo controlled evaluation of antiplatelet drugs in such populations is arguable. Secondly, overviews may be helpful when the balance of drug efficacy and risk is critical and the datasets in indi-
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