BACKGROUND

The benefit-risk profile of low-dose aspirin in primary prevention of cardiovascular disease is unclear. We sought to quantify upper gastrointestinal bleeding (UGIB) risk associated with low-dose aspirin in secondary versus primary prevention patients.

METHODS AND RESULTS

We performed a population-based nested case-control study using The Health Improvement Network (THIN) Database between 2000 and 2007. We identified 2049 cases of UGIB and 20,000 controls, frequency-matched to the cases on age, sex, and calendar year, who were subdivided into primary (without previous cardiovascular disease) and secondary (with previous cardiovascular disease) prevention populations. We estimated the relative risk of UGIB associated with the use of low-dose aspirin by multivariate logistic regression. The UGIB risk in patients taking low-dose aspirin relative to nonusers was significantly higher in the primary (adjusted relative risk, 1.90; 95% confidence interval, 1.59-2.26) than in the secondary (relative risk, 1.40; 95% confidence interval, 1.14-1.72; P value for the difference=0.0014) prevention cohort. However, as the baseline risk of UGIB was lower in the primary than in the secondary prevention cohort, numbers needed to harm per 1 year of low-dose aspirin use were 601 and 391 for primary and secondary prevention, respectively.

CONCLUSIONS

The relative risk of UGIB in patients taking low-dose aspirin is higher when used for primary than for secondary cardiovascular disease prevention, but this difference is more than compensated by the lower baseline risk in the primary prevention population. Such estimates are important for an assessment of the net clinical benefit in primary prevention.