Theme

PCABs vs. PPIs: Superior Nighttime Efficacy Meets Improved Safety

Source
Source: Data derived from a nationwide cohort study published in the Journal of Korean Medical Science (2026) regarding depression risk with acid suppressants, and a systematic review and meta-analysis published in Esophagus (2026) regarding nighttime GERD symptoms.

Comparative analysis of 6.1M+ Patients (Neuropsychiatric Safety) & 3 RCTs (Nocturnal Efficacy)

Nocturnal Heartburn Resolution
2.29x

Higher likelihood of complete resolution with PCABs vs. PPIs.

Clinical Recommendation

Shift preference to PCABs (Tegoprazan/Vonoprazan) for:

  • Patients with Nocturnal Acid Breakthrough.
  • Patients with pre-existing risk factors for Depression.

Nighttime Symptom Resolution

Meta-analysis of 3 RCTs (n=2,589)

Depression Risk (Adjusted OR)

Retrospective Cohort (n=6,104,743)

Study 1: Safety
  • Design: Nationwide Retrospective Cohort.
  • Population: 6.1M+ patients (18–80y).
  • Method: PSM (1:1).
  • Duration: Up to 1,200 days.
Study 2: Efficacy
  • Design: Systematic Review & Meta-Analysis.
  • Source: 3 RCTs (PCAB vs. PPI).
  • Sample: n=2,589 (EE or NERD).
  • Duration: 2 to 8 weeks.
General Safety

PCABs showed no significant increase in adverse events vs PPIs.

TEAE Risk Ratio 0.88 (p=0.62)
AbbreviationsQuick
aOR: adjusted odds ratio; CI: confidence interval; EE: erosive esophagitis; FPZ: fexuprazan; GERD: gastroesophageal reflux disease; HIRA: Health Insurance Review and Assessment Service; NERD: non-erosive reflux disease; OR: odds ratio; PCAB: potassium-competitive acid blocker; PPI: proton pump inhibitor; PSM: propensity score matching; RCT: randomized controlled trial; RR: risk ratio; TEAE: treatment-emergent adverse event; TPZ: tegoprazan; VPZ: vonoprazan.
Bibliography8
  1. Kim S, Kim JS. Risk of Depression Related to Use of Proton Pump Inhibitors and Tegoprazan: A Nationwide Cohort Study. J Korean Med Sci. 2026 Jan 12;41(2):e43. (DOI: 10.3346/jkms.2026.41.e43 | link)
  2. Koo TH, Fass R. A systematic review and meta-analysis of randomized controlled trials: the effect of potassium-competitive acid blockers on nighttime symptoms of gastroesophageal reflux disease. Esophagus. 2026 Jan 12. (link)
  3. Simadibrata DM, Syam AF, Lee YY. A comparison of efficacy and safety of potassium-competitive acid blocker and proton pump inhibitor in gastric acid-related diseases: a systematic review and meta-analysis. J Gastroenterol Hepatol 2022;37(12):2217-28.
  4. Huang WS, Bai YM, Hsu JW, et al. Use of proton pump inhibitors and risk of major depressive disorder: a nationwide population-based study. Psychother Psychosom 2018;87(1):62-4.
  5. Laine L, et al. Phase III Trial of Vonoprazan versus Lansoprazole for Healing and Maintenance of Healing of Erosive Esophagitis. 2023. (NCT04124926)
  6. Lee et al. Randomized Phase 3 Trial of Fexuprazan Versus Esomeprazole in Patients With Erosive Esophagitis. 2022. (NCT03736369)
  7. Jackson MA, Goodrich JK, Maxan ME, et al. Proton pump inhibitors alter the composition of the gut microbiota. Gut 2016;65(5):749-56.
  8. Freedberg DE, Kim LS, Yang YX. The risks and benefits of long-term use of proton pump inhibitors: expert review and best practice advice from the American Gastroenterological Association. Gastroenterology 2017;152(4):706-15.