PPIs and GI bleeding risk in low-dose aspirin users

  • García Rodríguez LA & al.
  • J Clin Med
  • 28 Mar 2020

  • curated by Sarfaroj Khan
  • UK Clinical Digest
Access to the full content of this site is available only to registered healthcare professionals. Access to the full content of this site is available only to registered healthcare professionals.


  • Patients using low-dose aspirin for cardiovascular prophylaxis who were co-prescribed a proton pump inhibitor (PPI) and continued for at least 1 month were at a lower risk of upper gastrointestinal bleeding (UGIB) than those who discontinued PPI therapy.
  • However, short- or long-term co-therapy with a PPI had no effect on lower gastrointestinal bleeding (LGIB) risk.

Why this matters

  • Findings support previous reports that PPIs are effective as protective agents against low-dose aspirin-related UGIB.
  • Physicians should consider prompt PPI co-prescription as delaying use is associated with an increased risk of UGIB.

Study design

  • This population-based observational study used UK primary care data and included 199,079 new users of low-dose aspirin and a 1:1 matched non-users at the start of follow-up who were followed for a maximum of 14 years (mean 5.4 years).
  • 987 UGIB cases, 2160 UGIB controls; and 1428 LGIB cases, 4100 LGIB were identified as current users of low-dose aspirin.
  • Funding: Bayer AG.

Key results

  • UGIB risk:
    • Concomitant current use of low-dose aspirin and PPI for >1 month was associated with a lower risk of UGIB (OR, 0.69; 95% CI, 0.54-0.88); the risk was more than 2-fold for ≤1 month PPI use (OR, 2.65; 95% CI, 1.62-4.30).
    • ORs for PPI initiation on/before the start of aspirin therapy and after the start of aspirin therapy were 1.66 (95% CI, 0.63-4.36) and 3.05 (95% CI, 1.75-5.33) respectively.
  • LGIB risk:
    • PPI was not associated with a change in LGIB risk (PPI use >1 month: OR 0.98, 95% CI: 0.81–1.17; ≤1 month use: OR, 1.12; 95% CI, 0.73-1.71).
    • The lack of association was still evident regardless of the timing of PPI initiation in relation to the start of low-dose aspirin therapy.


  • Possibility of residual confounding.
  • Possible misclassification of PPI use.