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Aspirin in Cardiovascular Disease

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Summary

Although other mechanisms may be contributory, the antithrombotic properties of aspirin derive predominantly from its platelet-inhibitory effects. These are mediated via irreversible acetylation of platelet cyclo-oxygenase with subsequent blockade of platelet thromboxane synthesis. Long term administration of doses of aspirin as low as 20mg daily depresses platelet thromboxane formation by more than 90%; however, higher doses appear to be necessary to prevent thromboxane-dependent platelet activation in vivo. While there is evidence of biochemical selectivity with low doses of aspirin, significant reduction of the platelet-inhibitory eicosenoid, prostacyclin, occurs even at dosages ranging from 20 to 40mg daily.

The ability of aspirin to prevent the occurrence or recurrence ofvaso-occlusion has been extensively investigated. In the secondary prevention of myocardial infarction 7 placebocontrolled trials involving more than 15,000 patients have been completed. The dose of aspirin varied from 300 to 1500mg daily. Although none of the individual trials produced statistically significant reductions in total or coronary mortality, taken together the results are highly suggestive of a beneficial effect of aspirin. Similarly, 2 recent studies in patients with unstable angina demonstrated a protective effect of aspirin against acute myocardial infarction and death While each study employed widely different doses of aspirin (324mg and 1250mg daily) similar reductions in mortality were reported. The effects of aspirin on the prevention of coronary artery bypass graft occlusion have been evaluated in 9 trials. Aspirin in doses of 100 to 975mg daily was shown to be of benefit in preventing early (< 6 months) graft occlusion, particularly when therapy was started within 24 hours of operation. In patients with prosthetic vascular grafts of the lower limbs, aspirin has been shown to reduce platelet deposition, however further controlled trials will be required to establish the patient population most likely to benefit and, as in all these studies, the optimum dose of aspirin to employ.

In patients with prosthetic heart valves it is clear that aspirin alone is insufficient to prevent thromboembolic complications and when administered as an adjunct to anticoagulant therapy it is associated with a high incidence of bleeding. In contrast, there is convincing evidence from several studies for the efficacy of aspirin in doses of 990 to 1300mg daily in the prevention of stroke and death in patients with transient ischaemic attacks.

Overall, the results of these clinical studies suggest that the maximum benefit of aspirin is likely to be achieved by its administration early in the process of thrombosis when platelet-dependent mechanisms appear to be most important. Future applications for the use of aspirin include the evaluation of biochemically selective regimens of aspirin in modulating platelet activation during acute vascular occlusion and investigation of its potential role in the primary prevention of cardiovascular disease.

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  1. The Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN, 37232, USA

    Irene A. G. Reilly &  G. A. FitzGerald

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Reilly, I.A.G., FitzGerald, G.A. Aspirin in Cardiovascular Disease. Drugs 35, 154–176 (1988). https://doi.org/10.2165/00003495-198835020-00005

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