Protective effect of proton pump inhibitor against gastrointestinal bleeding in patients receiving oral anticoagulants: a systematic review and meta-analysis

Abstract

Abstract Background The concurrent use of proton pump inhibitor (PPI) in oral anticoagulant (OAC) treated patients may be associated with a lower risk of gastrointestinal bleeding (GIB), but evidence is still conflicting according to individual OACs. Purpose We conducted a meta-analysis to estimate the risk of GIB in patients with OAC and PPI co-therapy. Methods A systematic search of PubMed, EMBASE, and Cochrane was performed for studies reporting GIB risk in OAC and PPI co-therapy. Primary outcomes were total GIB and major GIB events. We calculated pooled estimates of GIB risk by a random-effect meta-analysis and reported as odds ratios (OR) and 95% CI. Stratified analyses according to the origin of GIB, ethnic groups, individual OACs, and the presence of underlying GIB risk factors were performed. Results A total of 10 studies (1 randomized controlled study and 9 observational studies) and 1,970,931 patients who received OAC were included. OAC and PPI co-therapy were associated with a lower risk of total GIB, and major GIB; OR (95% CI) was 0.67 (0.62–0.74) for total GIB and 0.68 (0.63–0.75) for major GIB, respectively. Among total GIB, only the risk of upper GIB was lower with OAC and PPI co-therapy (OR 0.67, 95% CI 0.64–0.70). No difference in the lower risk of primary GIB outcomes of PPI co-therapy was observed between Asians and non-Asians (p-for-difference, total GIB=0.695, major GIB=0.748, respectively) and among individual OACs except for edoxaban. The protective effect of PPI on total GIB was more significant in high-risk patients, defined as those with concurrent medication of antiplatelets or non-steroidal anti-inflammatory drugs (OR 0.62, 95% CI 0.52–0.73) and presence of high bleeding risk factors such as previous GIB history, HAS-BLED score ≥3, or underlying gastrointestinal diseases. (OR 0.65, 95% CI 0.61–0.70). Conclusion In patients who receive OAC, the use of PPI co-therapy was associated with a lower risk of total GIB and major GIB irrespective of ethnic group and OAC type except for edoxaban. PPI co-therapy can be considered particularly in patients on concomitant NSAID and antiplatelet use or patients with high GIB risk factors. Funding Acknowledgement Type of funding sources: None.