Comparative risk of pneumonia and acute exacerbation between P-CAB and PPI use in patients with COPD and GERD.

Potassium-competitive acid blockers (P-CABs) are newer gastric acid suppressants used to treat gastroesophageal reflux disease (GERD), but evidence regarding their respiratory safety compared with proton pump inhibitors (PPIs) in patients with chronic obstructive pulmonary disease (COPD) remains limited. We conducted a target trial emulation study using the Korean National Health Insurance database. Patients aged ≥40 years with COPD who initiated P-CAB or PPI for GERD between 2019 and 2022 were included. Follow-up continued from treatment initiation until the earliest occurrence of the outcome, treatment discontinuation, switching to another drug class, death, or the end of the study period. The outcome was the occurrence of pneumonia or moderate-to-severe COPD exacerbations. Propensity score matching (1:3) was applied, and hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Among the 560,987 eligible patients, 4671 P-CAB users and 14,013 PPI users were included after matching. P-CAB was not significantly associated with the risk of respiratory events compared with PPI, but a trend toward lower risks for pneumonia (aHR, 0.76; 95% CI, 0.54-1.07) and severe exacerbations (aHR, 0.60; 95% CI, 0.32-1.14) was observed. In patients with a Charlson Comorbidity Index ≤1, the risk of severe exacerbations was significantly lower (aHR, 0.31; 95% CI, 0.11-0.88). P-CABs showed lower risks of pneumonia and severe exacerbations compared with PPIs, although the differences were not statistically significant. Further long-term studies across diverse patient subgroups are warranted.