Proton Pump Inhibitors Linked to Lower Risk for Upper GI Bleeding in Patients Prescribed Anticoagulants

Researchers explored the role of antisecretory therapy in the prevention of upper gastrointestinal bleeding in patients who are prescribed anticoagulants.

Use of proton pump inhibitors (PPIs) may reduce the risk for upper gastrointestinal bleeding (UGIB) in patients who are prescribed oral anticoagulants, according to study results published in the American Journal of Medicine.

Researchers conducted a systematic review and meta-analysis of the association of antisecretory therapies (PPIs and H2-receptor antagonists [H2RAs]) with UGIB, searching Embase, PubMed, Web of Science, Scopus, the Cochrane Library, and from establishment through April 7, 2021.

Eligible studies included patients aged 18 years and older, who used warfarin or a direct oral anticoagulant (DOAC) at any dose. A total of 7 studies published between 2011 and 2021 were included — 2 case-control studies, 4 retrospective cohort studies, and 1 randomized controlled trial.

After 2 studies were excluded from the meta-analysis, the pooled relative risk (RR) was 0.67 (95% CI, 0.61-0.74) with low statistical heterogeneity (I2=15%, P =.32).

In 1 case-control study of patients using warfarin, PPI use was associated with an adjusted RR for UGIB of 0.48 (95% CI, 0.22-1.04). In a different study examining patients with atrial fibrillation and a history of UGIB, the pooled estimate of PPI effect for warfarin and DOACs resulted in a hazard ratio (HR) of 0.67 (95% CI, 0.57-0.78) with low heterogeneity.

An additional study found that the decrease in UGIB was greater (P =.01) in patients who used antiplatelet drugs or nonsteroidal antiinflammatory drugs (NSAIDs) (adjusted HR, 0.55; 95% CI, 0.39-0.77; adjusted annual risk difference, -1.3%; 95% CI, -1.7% to -0.7%; number needed to treat, 77; 95% CI, 59-143) compared with nonusers (adjusted HR, 0.86; 95% CI, 0.70-1.06; adjusted annual risk difference, -0.1%; 95% CI, -0.3% to 0.06%).

In the 1 observational study that assessed H2RAs, the RR was 0.69 (95% CI, 0.24-2.02).

Study limitations included the presence of potential biases; heterogenous study populations and designs; the susceptibility of observational studies to misclassification of PPI, aspirin and NSAID use; and that some relevant studies may have been omitted.

“Our systematic review and meta-analysis suggest that PPIs reduce the risk [for] [UGIB] in anticoagulated patients but that the absolute benefits vary substantially depending on baseline risk,” the researchers noted. “For anticoagulated patients without additional risk factors for [UGIB], the benefit from PPIs is likely minimal. We believe that future guideline panels should incorporate our results and include a recommendation for PPI co-therapy in patients taking oral anticoagulants who have elevated baseline risk for [UGIB], including those using concomitant antiplatelet therapy or NSAIDs.”

Disclosure: One of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Kurlander JE, Barnes G, Fisher A, et al. Association of anti-secretory drugs with upper gastrointestinal bleeding in patients using oral anticoagulants: a systematic review and meta-analysis. Am J Med. Published online June 6, 2022. doi:10.1016/j.amjmed.2022.05.031