Role of Proton Pump Inhibitors in Prevention of Upper Gastrointestinal Bleeding in Patients on Dual Antiplatelet Therapy: Systematic Review and Meta-Analysis

BACKGROUND: Dual antiplatelet therapy (DAPT) with oral P2Y12 inhibitors and aspirin is crucial for patients with acute coronary syndrome (ACS) and postpercutaneous coronary interventions (PCI). Concomitant proton pump inhibitor (PPI) therapy with DAPT can potentially reduce the risk of upper gastrointestinal bleeding (UGIB). AIM: We conducted a meta-analysis of randomized controlled trials to evaluate the prevention of UGIB with concomitant use of PPI with DAPT. METHODS: We reviewed several databases to identify randomized controlled trials comparing the risk of UGIB in patients using DAPT + PPI vs. DAPT with no PPI or DAPT + Histamine 2 receptor antagonists. Our outcomes of interest were UGIB, major cardiovascular adverse events (MACE), myocardial infarction, and all-cause mortality. We calculated pooled risk ratio (RR) with 95% confidence intervals (CI) for all of the outcomes and analyzed data using random effect model. Heterogeneity was assessed using I2 statistic. RESULTS: Seven randomized controlled trials comprising 6708 patients were included. Rate of UGIB was significantly lower in the PPI + DAPT group, RR (95% CI): 0.39 (0.25-0.60). There was no significant difference in the rate of MACE between groups, RR (95% CI): 0.87 (0.69-1.10). Rate of MI was also not significantly different between groups, RR (95% CI): 0.93 (0.75-1.14). Rate of mortality was significantly lower in the PPI + DAPT group, RR (95% CI) 0.46 (0.27-0.80). CONCLUSIONS: Our meta-analysis demonstrates that adding PPI therapy to DAPT significantly lowers the risk of UGIB and all-cause mortality, without adversely affecting major cardiovascular outcomes.