Effect of a potassium-competitive acid blocker on the gut microbiota in patients undergoing percutaneous coronary...

Proton pump inhibitors (PPIs) are routinely used in patients undergoing percutaneous coronary intervention (PCI) to prevent gastrointestinal bleeding associated with dual-antiplatelet therapy (DAPT). However, long-term PPI use has been linked to gut microbiota dysbiosis. Tegoprazan, a potassium-competitive acid blocker (P-CAB), may exert distinct effects on the gut microbiome. This study compared the longitudinal effects of tegoprazan and pantoprazole on gut microbiota composition in patients with angina undergoing PCI.

This prospective, randomized, controlled pilot study randomized 38 patients 1:1:1 to tegoprazan 50 mg once daily, pantoprazole 40 mg once daily, or no acid-suppressive therapy for 24 weeks. Five participants did not provide baseline fecal samples, and nine discontinued participation before week 24. Thus, 24 participants with paired baseline and week-24 fecal samples were included in the final analysis. Fecal samples were analyzed using 16S rRNA gene sequencing.

No drug-related adverse events or gastrointestinal bleeding occurred in any group. Observed amplicon sequence variant (ASV) richness was significantly higher at week 24 than at baseline in the overall cohort (p = 0.003) and P-CAB group (p = 0.016), whereas the Shannon index showed no significant changes. Paired PERMANOVA with permutations restricted by patient ID revealed significant differences in Bray-Curtis beta diversity between baseline and week 24 in the P-CAB group (R² = 0.070, p = 0.031) and PPI group (R² = 0.059, p = 0.008), but not in the no acid-suppressive therapy group (R² = 0.021, p = 0.691). In the formal cross-arm analysis, the treatment group-by-visit interaction was not significant for Bray-Curtis beta diversity (R² = 0.021, pseudo-F = 0.505, p = 0.270). Although nominal within-arm taxonomic changes were observed, no treatment group-by-visit interaction survived Benjamini-Hochberg correction in ANCOM-BC2.

Tegoprazan was well tolerated, with no drug-related adverse events or gastrointestinal bleeding during the 24-week follow-up. Both acid-suppressive treatment groups showed modest longitudinal microbiome changes. The taxon-level findings were exploratory and hypothesis-generating and should not be interpreted as definitive evidence of treatment-specific differential effects. Larger, adequately powered studies are required to confirm these observations.