Low-dose aspirin and risk of upper/lower gastrointestinal bleeding by bleed severity: a cohort study with nested case-control analysis using primary care electronic health records from the United Kingdom

Introduction: Risks of low-dose aspirin-associated upper and lower gastrointestinal bleeds (UGIB/LGIB) may vary by severity and presence of cardiovascular disease (CVD). No study has quantified these risks for UGIB and LGIB in the same real-world study population. Patients and methods: Using UK primary care data, 199,049 new users of low-dose aspirin (75–300 mg/day) and 1:1 matched non-users were followed to identify incident UGIB (N = 1843)/LGIB (N = 2763) cases. Nested case-control analyses compared current low-dose aspirin vs. non-use on UGIB/LGIB risk. Results: Adjusted incidence rate ratios (ORs; 95% CIs) were 1.62 (1.42–1.86) for non-fatal UGIB, 1.63 (1.47–1.81) for non-fatal LGIB, 0.77 (0.51–1.16) for fatal UGIB, 1.29 (0.50–3.36) for fatal LGIB. For hospitalizations, adjusted ORs (95% CIs) were 1.55 (1.32–1.81) for UGIB and 1.89 (1.58–2.27) for LGIB; for referred only cases, they were 1.52 (1.26–1.84) for UGIB and 1.54 (1.37–1.73) for LGIB. In primary CVD prevention, adjusted ORs (95% CI) were 1.62 (1.38–1.90) for UGIB and 1.60 (1.42–1.81) for LGIB; in secondary CVD prevention, they were 1.16 (0.89–1.50) for UGIB and 1.67 (1.34–2.09) for LGIB. Conclusion: KEY MESSAGE: Low-dose aspirin is associated with an increased risks of non-fatal UGIB/LGIB but not fatal UGIB/LGIB.