Proton Pump Inhibitor Use, Gastrointestinal Bleeding Reduction, and Long-Term Prognosis After Percutaneous Coronary Intervention

Proton pump inhibitors (PPI) reduce gastrointestinal bleeding (GIB) after percutaneous coronary intervention (PCI), but their impact on mortality and major adverse cardiovascular events (MACE) remains unclear. This study investigated the association between PPI-related GIB reduction and MACE and mortality using a real-world database. We analyzed 6,457 patients undergoing PCI (2013 to 2019), using the Clinical Deep Data Accumulation System including electronic medical records from 7 Japanese hospitals. Patients were grouped by PPI use. The primary outcome was GIB and secondary outcomes were all-cause mortality and MACE. Propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and Cox regression were used to estimate hazard ratios. To estimate causal inference, mediation analysis was conducted to assess the indirect effects of PPI use via GIB reduction. PSM and IPTW analyses revealed a lower GIB incidence in the PPI group (PSM: <0.1%, IPTW: 1.6%) than in the non-PPI group (PSM: 2.3%, IPTW: 2.7%). No significant association was found between PPI use and all-cause death or MACE. However, in patients with acute coronary syndrome (ACS), IPTW analysis indicated that PPI use was associated with lower all-cause death (HR: 0.582, 95% CI: 0.364 to 0.931) and MACE (HR: 0.570, 95% CI: 0.344 to 0.946). Importantly, mediation analysis suggested that GIB reduction partially mediated the association between PPI use and lower mortality. In conclusion, PPI use after PCI was associated with lower GIB risk. In ACS patients, it may be associated with a reduction in all-cause mortality, partially mediated by GIB reduction.