Seventeen studies were included: 3 cohorts and 14 case-control studies. Three case-control studies were nested in a cohort. Ten case-control studies used matched designs. The total number of participants was not reported.
The pooled RR of UGIC associated with aspirin use was 2.6 (95% CI: 2.4, 2.7) when using a fixed-effect model, and 2.7 (95% CI: 2.2, 3.2) when using a random-effects model. However, the individual RR estimates were heterogeneous (p<0.001) and varied from 1.4 to 11.2. The overall RR of UGIC associated with aspirin use was 2.2 (95% CI: 2.1, 2.4) for cohort studies and nested case-control studies, which was significantly lower than that for non-nested case-control studies (RR 3.1, 95% CI: 2.8, 3.3).
Five studies addressed the effect of different daily doses of aspirin in their analyses. All of them found greater risks of UGIC for aspirin doses above 300 mg/day than for lower doses. However, the risk was still elevated for doses up to 300 mg/day.
Four studies reported data on aspirin formulation. The pooled RRs were 2.4 (95% CI: 1.9, 2.9) for enteric-coated aspirin formulations and 2.6 (95% CI: 2.3, 2.9) for plain preparations. Two studies found buffered aspirin not to be associated with a lower UGIC risk than regular aspirin; the pooled RRs were 4.1 (95% CI: 3.2, 5.1) and 5.3 (95% CI: 3.0, 9.2) for plain and buffered aspirin, respectively, in those two studies.
When the frequency of exposure was investigated (2 studies), the RR was higher for patients using aspirin regularly (RR 3.2, 95% CI: 2.6, 3.9) than for those using aspirin occasionally (RR 2.1, 95% CI: 1.7, 2.6). When duration of use was investigated (3 studies), the risk of UGIC associated with aspirin was higher during the first month of use (RR 4.4, 95% CI: 3.2, 6.1) than in subsequent months of treatment (RR 2.6, 95% CI: 2.1, 3.1).
The funnel plot did not suggest the presence of publication bias.