Objective:

To evaluate the evidence regarding the co-administration of proton pump inhibitors (PPIs) with non-vitamin K antagonist oral anticoagulants (NOACs) and their impact on gastrointestinal bleeding outcomes, emphasizing the clinical significance of these outcomes.

Approach:

Key Findings:

• PPI co-therapy in NOAC-treated AF patients was associated with reduced risks of UGIB hospitalization (weighted HR 0.825) and transfusion-requiring UGIB (weighted HR 0.798), noting the observational nature of the studies.
• A meta-analysis indicated lower odds of total and major GIB with PPI use (OR ∼0.67–0.68).
• Observational studies suggest PPI co-therapy may reduce hospitalization for UGIB and severe bleeding events, particularly in high-risk subgroups, while acknowledging potential biases.

Interpretation:

While PPI co-therapy may reduce UGIB risks in NOAC-treated patients, the evidence is primarily observational and subject to confounding, which may affect the reliability of the findings.

Limitations:

• Most data are observational and may be affected by confounding by indication.
• Findings have not been entirely consistent across different analytic designs, and heterogeneity may impact the overall conclusions.

Conclusion:

PPI co-therapy may be a pragmatic strategy for high-risk NOAC-treated patients, pending further randomized evidence to confirm these findings.

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