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Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients

BMJ 2002; 324 doi: (Published 12 January 2002) Cite this as: BMJ 2002;324:71
  1. Antithrombotic Trialists' Collaboration
  1. Correspondence to: Antithrombotic Trialists' Secretariat, Clinical Trial Service Unit, Radcliffe Infirmary, Oxford OX2 6HE


    Objective: To determine the effects of antiplatelet therapy among patients at high risk of occlusive vascular events.

    Design: Collaborative meta-analyses (systematic overviews).

    Inclusion criteria: Randomised trials of an antiplatelet regimen versus control or of one antiplatelet regimen versus another in high risk patients (with acute or previous vascular disease or some other predisposing condition) from which results were available before September 1997. Trials had to use a method of randomisation that precluded prior knowledge of the next treatment to be allocated and comparisons had to be unconfounded—that is, have study groups that differed only in terms of antiplatelet regimen.

    Studies reviewed: 287 studies involving 135 000 patients in comparisons of antiplatelet therapy versus control and 77 000 in comparisons of different antiplatelet regimens.

    Main outcome measure: “Serious vascular event”: non-fatal myocardial infarction, non-fatal stroke, or vascular death.

    Results: Overall, among these high risk patients, allocation to antiplatelet therapy reduced the combined outcome of any serious vascular event by about one quarter; non-fatal myocardial infarction was reduced by one third, non-fatal stroke by one quarter, and vascular mortality by one sixth (with no apparent adverse effect on other deaths). Absolute reductions in the risk of having a serious vascular event were 36 (SE 5) per 1000 treated for two years among patients with previous myocardial infarction; 38 (5) per 1000 patients treated for one month among patients with acute myocardial infarction; 36 (6) per 1000 treated for two years among those with previous stroke or transient ischaemic attack; 9 (3) per 1000 treated for three weeks among those with acute stroke; and 22 (3) per 1000 treated for two years among other high risk patients (with separately significant results for those with stable angina (P=0.0005), peripheral arterial disease (P=0.004), and atrial fibrillation (P=0.01)). In each of these high risk categories, the absolute benefits substantially outweighed the absolute risks of major extracranial bleeding. Aspirin was the most widely studied antiplatelet drug, with doses of 75-150 mg daily at least as effective as higher daily doses. The effects of doses lower than 75 mg daily were less certain. Clopidogrel reduced serious vascular events by 10% (4%) compared with aspirin, which was similar to the 12% (7%) reduction observed with its analogue ticlopidine. Addition of dipyridamole to aspirin produced no significant further reduction in vascular events compared with aspirin alone. Among patients at high risk of immediate coronary occlusion, short term addition of an intravenous glycoprotein IIb/IIIa antagonist to aspirin prevented a further 20 (4) vascular events per 1000 (P<0.0001) but caused 23 major (but rarely fatal) extracranial bleeds per 1000.

    Conclusions: Aspirin (or another oral antiplatelet drug) is protective in most types of patient at increased risk of occlusive vascular events, including those with an acute myocardial infarction or ischaemic stroke, unstable or stable angina, previous myocardial infarction, stroke or cerebral ischaemia, peripheral arterial disease, or atrial fibrillation. Low dose aspirin (75-150 mg daily) is an effective antiplatelet regimen for long term use, but in acute settings an initial loading dose of at least 150 mg aspirin may be required. Adding a second antiplatelet drug to aspirin may produce additional benefits in some clinical circumstances, but more research into this strategy is needed.

    What is already known on this topic

    What is already known on this topic Antiplatelet therapy is effective for short term treatment of patients with suspected acute myocardial infarction and unstable angina

    Long term treatment is beneficial for patients who have had a myocardial infarction, stroke, or transient ischaemic attack

    Daily aspirin doses of 75-325 mg are effective

    What this study adds

    What this study adds Antiplatelet therapy protects against vascular events among patients with stable angina, intermittent claudication, and (if oral anticoagulants are unsuitable) atrial fibrillation

    Antiplatelet therapy can be started promptly during acute presumed ischaemic stroke and continued long term

    Daily aspirin doses of 75-150 mg seem to be as effective as higher doses for long term treatments (and clopidrogel is an appropriate alternative for patients with a contraindication to aspirin)

    Short term addition of a glycoprotein IIb/IIIa antagonist to aspirin prevents vascular events in patients having percutaneous coronary intervention and those with unstable angina but causes increased bleeding


    • Editorial by FitzGerald

    • Funding Since the inception of this collaboration several years ago, staff and computing have been provided by grants from the Medical Research Council (United Kingdom), the Stroke Association, Chest, Heart and Stroke Scotland, Edinburgh University (Sir Stanley and Lady Davidson Fund); and by the Clinical Trial Service Unit and Epidemiological Studies Unit (Nuffield Department of Clinical Medicine, University of Oxford), which is supported by the Medical Research Council (United Kingdom), the British Heart Foundation, and the Imperial Cancer Research Fund. Support for the current cycle has also been contributed by a program grant from the European Union Biomed Programme (Contract number BMH-CT93-1552 plus supplementary agreement number 2), and by a Wellcome Training Fellowship for C Sudlow.

    • Competing interests The Clinical Trial Service Unit has received grants for independent research from AstraZeneca, Bristol-Myers Squibb, Hoffman-La Roche, Merck Sharp and Dohme, and Sanofi-Synthelabo. No grants were received from industry for the present cycle of analyses.

    • Embedded ImageDetails of the studies that were included, names of the collaborators, and a figure showing analyses of the proportional effects of treatment for different outcomes are available on

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