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

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). RESULTSFourteen 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 4 / 37 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.