Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials

Overview

The authors analyzed the current clinical trial evidence to determine the balance of benefits and harms of aspirin therapy in patients who have not had a heart attack or stroke compared to those with a history of heart disease or stroke. The two outcomes of interest were: 1) serious vascular events, which included heart attack, stroke and death from a cause connected with vascular disease, and 2) major bleeding. While aspirin use in those without disease resulted in a 12% reduction in serious vascular events, it also significantly increased (by 54%) major gastrointestinal and non-brain bleeding. The authors interpret these data to suggest that for primary prevention “aspirin is of uncertain net value.”

Methodology

The authors analyzed the current clinical trial evidence regarding the benefits and harms of aspirin use in individuals who have had a heart attack or stroke and in those not having such past health problems.

The analysis of aspirin for primary prevention included six clinical trials in participants without known vascular disease for a total of 95,000 individuals, 660,000 person-years of follow-up and 3,554 serious vascular events. The two outcomes of interest were: 1) serious vascular events, which included heart attack, stroke and death from a cause connected with vascular disease, and 2) major bleeding. Similar strategies were used to analyze aspirin’s benefits and harms in participants with a previous heart attack or stroke.

Results

  • Aspirin use results in a 12% reduction in serious vascular events. In a population of 10,000 people taking aspirin there would be 51 events per year versus 57 with no aspirin, mainly due to a 20% reduction in non-fatal heart attacks. The number needed to treat for ten years to prevent one serious event would be 150 individuals.

  • At the same time, aspirin increases major gastrointestinal and extracranial bleeds (outside of the head) by 54%, so that for 10,000 people there would be 10 major bleeding problems if they took aspirin versus 7 if they did not take aspirin. This equates to a number needed to treat with aspirin for 10 years to produce one additional case of major bleeding would be 333 individuals.

  • The reduction in serious vascular events was similar by gender, although the types of events included in these composite outcomes were very different for men and women.

  • For patients with known heart attack or stroke, aspirin use has substantial benefits that outweigh its risk.

Conclusions

  • Aspirin provides substantial benefit in the secondary prevention of cardiovascular events. The analysis of those with known disease (secondary prevention) confirmed the substantial benefit of aspirin that has been well established.

  • Aspirin provides benefits and harms for the primary prevention of cardiovascular disease. Aspirin use resulted in a 12% reduction in serious vascular events, but it also significantly increased (by 54%) major gastrointestinal and non-brain bleeding. The authors interpret these data to suggest that “aspirin is of uncertain net value,” implying that for patients like those included in the trials there is not enough benefit to offset known harms. This conclusion is controversial. If the authors had considered bleeding episodes to be less important than heart attacks a more favorable assessment would have occurred.