Impact of proton pump inhibitors on the risk of small bowel or colorectal bleeding: A systematic review and meta‐analysis

Abstract

BackgroundSeveral studies have suggested that the mucosal protective effects of proton pump inhibitors (PPIs) do not extend beyond the duodenum; however, PPIs may cause lower gastrointestinal (LGI) injury, although these relationships have not yet been fully elucidated.MethodsWe searched all the relevant studies published until September 2022 that examined the risk of PPIs for LGI bleeding. We performed a meta‐analysis of the risk of LGI bleeding (small bowel (SB) or colorectal bleeding) between PPI users and non‐users. A subgroup analysis of patients consuming aspirin or nonsteroidal anti‐inflammatory drugs (NSAIDs) was also performed.ResultsTwelve studies with 341,063 participants were included in this meta‐analysis. The use of PPIs was associated with the risk of LGI bleeding (odds ratio [OR] [95% confidence interval [CI]] = 1.42 [1.16–1.73]; hazard ratio [HR] [95% CI] = 3.23 [1.56–6.71]). An association between PPI use and the risk of LGI bleeding was also identified in the subgroup of aspirin or NSAID users (OR [95% CI] = 1.64 [1.49–1.80]; HR [95% CI] = 6.55 [2.01–21.33]). In the bleeding site‐specific analyses, the risk of SB bleeding was associated with PPI use (OR [95% CI] = 1.54 [1.30–1.84]).ConclusionsPPI use was associated with an increased risk of LGI bleeding, particularly SB bleeding. This association was particularly pronounced among aspirin and NSAID users. Inappropriate PPI prescriptions should be avoided in patients with LGI bleeding and a low risk of upper gastrointestinal disease.

Reduced risk of gastrointestinal bleeding associated with eupatilin in aspirin plus acid suppressant users: nationwide population-based study

“…In a recent meta-analysis based on 12 studies with 341,063 participants, PPI use was associated with an increased risk of lower GI bleeding, particularly in the small bowel. This association was particularly pronounced among patients taking aspirin or NSAIDs [35]. In a previous study, the following strategies against NSAID-induced GI injuries were recommended [32].…”

DA-9601 has protective effects comparable to those of proton pump inhibitor and rebamipide against nonsteroidal anti-inflammatory drugs-induced upper and lower gastrointestinal bleeding in patients with rheumatoid arthritis: A nationwide study using Korean Health Insurance Review and Assessment Service database

“…PPIs are 1 of the most widely used prophylactic medications for NSAIDs-induced PUD; nonetheless, recent evidence suggests that PPI can induce bacterial overgrowth in the small bowel, subsequently increasing the risk of lower GI bleeding, which is more pronounced in patients using NSAIDs. [26] In addition, as mentioned above, long-term PPI use can be accompanied by various adverse effects in organs beyond the GI tract. Thus, achieving a risk-benefit balance when choosing PPIs for the long-term prevention of NSAIDs-induced GI complications is essential.…”