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 135000 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 (75-150mg daily) is an effective antiplatelet regimen for long term use,but in acute settings an initial loading dose of at least 150mg 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.