Proton pump inhibitors for prevention of upper and lower gastrointestinal bleeding in patients taking aspirin: a systematic review and meta-analysis.

Siqi Jia, Yuhang Yin, Wenhui Huo, Huiyuan Lu, Yanhong Gao, Xingshun Qi

Journal: European journal of clinical pharmacology 2026;82(8):

PMID: 42479073

Abstract

OBJECTIVES

Proton pump inhibitors (PPIs) are recommended for the prevention of aspirin-associated gastrointestinal mucosal injury, but emerging evidence indicates that PPIs may increase the risk of lower gastrointestinal bleeding (LGIB). This meta-analysis aimed to comprehensively evaluate the effects of PPIs on gastrointestinal bleeding (GIB).

METHODS

Major electronic databases were searched to identify the studies evaluating the differences between PPIs versus placebo/blank, no-PPI, histamine-2 receptor antagonists (H₂RAs), mucosal protective agents (MPAs), and potassium-competitive acid blockers (P-CABs) in preventing aspirin-associated GIB. Risk ratios (RRs) with their 95% confidence intervals (CIs) were calculated.

RESULTS

Sixteen randomized controlled trials (RCTs) and 14 non-RCTs were included. PPIs group had significantly lower risk of upper gastrointestinal bleeding (UGIB) than placebo/blank group (7 RCTs, RR = 0.30, 95%CI = 0.19-0.46; 2 non-RCTs, RR = 0.05, 95%CI = 0.01-0.42), no-PPI group (7 non-RCTs, RR = 0.50, 95%CI = 0.38-0.66), H₂RAs group (5 RCTs, RR = 0.21, 95%CI = 0.09-0.53; 4 non-RCTs, RR = 0.12, 95%CI = 0.03-0.52), and MPAs group (4 RCTs, RR = 0.24, 95%CI = 0.10-0.58), but statistically similar (2 non-RCTs, RR = 1.18, 95%CI = 0.77-1.79) or significantly higher (1 RCT, log-rank P = 0.018 and 0.019) risk of UGIB than P-CABs group. PPIs group had significantly higher risk of lower gastrointestinal bleeding (LGIB) than no-PPI group (3 non-RCTs, RR = 2.85, 95%CI = 1.85-4.38), but statistically similar risk of LGIB to H₂RAs group (2 RCTs, RR = 1.88, 95%CI = 0.30-11.82).

CONCLUSIONS

The evidence from RCTs and non-RCTs suggests the advantages of PPIs over placebo/blank, no-PPI, H₂RAs, and MPAs for the prevention of UGIB in aspirin users. The evidence regarding PPIs and LGIB in aspirin users is from non-RCTs alone, and suggests their potential harms.

Address: Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of the Shenyang Pharmaceutical University), No. 83 Wenhua Road, Shenyang, 110840, Liaoning Province, China.; Postgraduate College, Shenyang Pharmaceutical University, Shenyang, China.; General Hospital of Northern Theater Command, China Medical University, Shenyang, China.; Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of the Shenyang Pharmaceutical University), No. 83 Wenhua Road, Shenyang, 110840, Liaoning Province, China.; Department of Gastroenterology, General Hospital of Northern Theater Command (Teaching Hospital of the Shenyang Pharmaceutical University), No. 83 Wenhua Road, Shenyang, 110840, Liaoning Province, China. [email protected].; Postgraduate College, Shenyang Pharmaceutical University, Shenyang, China. [email protected].; General Hospital of Northern Theater Command, China Medical University, Shenyang, China. [email protected].

DOI: 10.1007/s00228-026-04135-2

MeSH Terms: Humans, Gastrointestinal Hemorrhage, Proton Pump Inhibitors, Aspirin, Histamine H2 Antagonists