Aspirin, Vascular Disease and Cancer: 50 Years of Controversy and the Jury’s Still Out!

The story of aspirin and vascular disease starts with John O Brien, a haematologist in Portsmouth in the 1960s, who reported that the ingestion of 150mg of aspirin substantially reduced the aggregation of platelets On the basis of this finding, and the assumption that the incidence of thrombosis would be reduced, O'Brien persuaded the UK Medical Research Council in 1968 to set up a randomised trial of aspirin Three hundred and three surgical patients in four UK hospitals were randomly given 600mg aspirin or a placebo once preoperatively and on five post-operative days. The outcome was deep vein thrombosis diagnosed by I125labelled fibrinogen. The conclusion, written presumably by Austin Heady the statistician on the team, was: 'aspirin administration has not even a marginal effect on the frequency of DVT'. This dismissal now appears rather confident in view of the later finding of clinically important reductions by aspirin in venous thrombosis and pulmonary embolism after surgery O Brien was convinced that venous thrombosis had been an inappropriate test of aspirin in the reduction of thrombosis but he failed to persuade MRC to conduct another trial. However, persuaded by work in the Welsh National School of Medicine in the 1960s on aspirin, platelet 'clumping ' and 'infarctoid cardiopathy',[4-6] Archie Cochrane agreed that a trial of aspirin and vascular mortality be set up in South Wales. 1,400 postmyocardial infarction patients agreed to be randomised to 325mg aspirin orally per day the dose and frequency suggested for the trial by O'Brien. After two years, aspirin taking was associated with a 24% reduction in all-cause mortality Because of uncertainties in the clinical diagnosis of infarction, the protocol for the study had stated that all-cause mortality would be the sole outcome by which aspirin would be judged. The reduction failed to achieve significance at P>0.05 and the report of the trial was therefore published under the heading 'For debate'. Under this same heading the BMJ published a remarkable observational study by Martin Vessey who had been on the steering Committee for the earlier MRC trial Together with Hershel Jick in Boston USA, Vessey looked for unknown adverse