Proton pump inhibitors for gastrointestinal bleeding prevention after percutaneous coronary intervention: Comparing evidence in dual antiplatelet therapy

Abstract

BACKGROUND

Dual antiplatelet therapy (DAPT), combining aspirin with a P2Y12 inhibitor, is the standard of care following percutaneous coronary intervention (PCI), but it significantly increases the risk of gastrointestinal (GI) bleed. Proton pump inhibitors (PPIs) are commonly co-prescribed to mitigate this risk, though concerns about potential drug interactions, particularly with clopidogrel, have led to clinical uncertainty.

AIM

To evaluate the impact of PPI co-therapy on GI bleed, major bleed, upper and lower GI bleed, and all-cause mortality in patients receiving DAPT after PCI.

METHODS

A systematic literature search of PubMed, Cochrane Library, and Google Scholar was conducted through March 2025. Eligible studies included randomized controlled trials (RCTs) and observational studies reporting outcomes in adult patients receiving DAPT with or without PPI use. Primary outcomes included GI bleed, major bleed, upper and lower GI bleed, and all-cause mortality. A random-effects model was used to estimate pooled relative risks (RRs) with 95% confidence intervals (CIs).

RESULTS

Fourteen studies (6 RCTs and 8 observational studies) involving 106954 patients (101567 in observational studies; 5387 in RCTs) were included. RCTs found that PPI use was associated with a significantly reduced risk of overall GI bleed (RR = 0.39; 95%CI: 0.21-0.74; P = 0.004), with this effect being most prominent in omeprazole subgroup (RR = 0.45; 95%CI: 0.21-0.96; P = 0.04). Moreover, PPI use significantly lowered the risk of upper GI bleed in RCTs (RR = 0.50; 95%CI: 0.28-0.89; P = 0.02). In observational studies, the PPI group was associated with an increased risk of lower GI bleed (RR = 1.65; 95%CI: 1.31-2.06; P < 0.0001) and a decreased major bleed events (RR = 0.59; 95%CI: 0.48-0.72; P < 0.00001), these effects were not studied in RCTs. Observational studies failed to show any significant effect on all-cause mortality, total GI bleed, or upper GI bleed.

CONCLUSION

PPI co-therapy significantly reduces risk of overall GI bleed in DAPT-treated patients post-PCI. However, a modest increase in hypothesis-generated lower GI bleed found only in observational studies underscores the need for further studies to explore this association.

Keywords: Dual antiplatelet therapy; Percutaneous coronary intervention; Proton pump inhibitors; Gastrointestinal bleeding; All-cause mortality

Core Tip: Proton pump inhibitor (PPI) co-therapy remains an effective strategy for preventing upper gastrointestinal (GI) bleeding in patients receiving dual antiplatelet therapy after percutaneous coronary intervention. This systematic review and meta-analysis separately evaluated randomized trials and observational studies, demonstrating consistent protection against upper GI bleeding while highlighting differences in effect estimates across study designs. Observational findings regarding lower GI bleeding, major bleeding, and all-cause mortality should be interpreted cautiously because of lower certainty and potential confounding. These findings support current guideline recommendations for PPI use while emphasizing the need for further high-quality studies to clarify long-term safety and comparative efficacy among individual PPIs.