Systematic Review and Meta-Analysis of Randomised Trials to Ascertain Fatal Gastrointestinal Bleeding Events Attributable to Preventive Low-Dose Aspirin: No Evidence of Increased Risk

Background: Aspirin has been shown to lower the incidence and the mortality of vascular disease and cancer but its wider adoption appears to be seriously impeded by concerns about gastrointestinal (GI) bleeding. Unlike heart attacks, stroke and cancer, GI bleeding is an acute event, usually followed by complete recovery. We propose therefore that a more appropriate evaluation of the risk-benefit balance would be based on fatal adverse events, rather than on the incidence of bleeding. We therefore present a literature search and meta-analysis to ascertain fatal events attributable to low-dose aspirin. Methods: In a systematic literature review we identified reports of randomised controlled trials of aspirin in which both total GI bleeding events and bleeds that led to death had been reported. Principal investigators of studies in which fatal events had not been adequately described were contacted via email and asked for further details. A meta-analyses was then performed to estimate the risk of fatal gastrointestinal bleeding attributable to low-dose aspirin. Results: Eleven randomised trials were identified in the literature search. In these the relative risk (RR) of ‘major’ incident GI bleeding in subjects who had been randomised to low-dose aspirin was 1.55 (95% CI 1.33, 1.83), and the risk of a bleed attributable to aspirin being fatal was 0.45 (95% CI 0.25, 0.80). In all the subjects randomised to aspirin, compared with those randomised not to receive aspirin, there was no significant increase in the risk of a fatal bleed (RR 0.77; 95% CI 0.41, 1.43). Conclusions: The majority of the adverse events caused by aspirin are GI bleeds, and there appears to be no valid evidence that the overall frequency of fatal GI bleeds is increased by aspirin. The substantive risk for prophylactic aspirin is therefore cerebral haemorrhage which can be fatal or severely disabling, with an estimated risk of one death and one disabling stroke for every 1,000 people taking aspirin for ten years. These adverse effects of aspirin should be weighed against the reductions in vascular disease and cancer.