Determination of who may derive most benefit from aspirin in primary prevention: Subgroup results from a randomised controlled trial

Abstract

Objective. To determine which groups of patients may derive particular benefit or experience harm from the use of low dose aspirin for the primary prevention of coronary heart disease. Design. Randomised controlled trial. Setting. 108 group practices in the Medical Research Council's general practice research framework who were taking part in the thrombosis prevention trial Participants. 5499 men aged between 45 and 69 years at entry who were at increased risk of coronary heart disease. Main outcome measures. Myocardial infarction, coronary death, and stroke. Results. Aspirin reduced coronary events by 20%. This benefit, mainly for non-fatal events, was significantly greater the lower the systolic blood pressure at entry (interaction P = 0.0015), the relative risk at pressures 130 mmHg being 0.33 compared with 0.94 at pressures > 145 mmHg. Aspirin also reduced strokes at low but not high pressures, the relative risks being 0.41 and 1.42 (P = 0.006) respectively. The relative risk of all major cardiovascular events - that is, the sum of coronary heart disease and stroke - was 0.59 at pressures < 130 mmHg compared with 1.08 at pressures > 145 mmHg (P = 0.0001). Conclusion. Even with the limitations of subgroup analyses the evidence suggests that the benefit of low dose aspirin in primary prevention may occur mainly in those with lower systolic blood pressures, although it is not clear even in these men that the benefit outweighs the potential hazards. Men with higher pressures may be exposed to the risks of bleeding while deriving no benefit through reductions in coronary heart disease and stroke..