A systematic review and meta-analysis of randomized controlled trials: the role of potassium-competitive acid blockers in endoscopy-negative reflux disease

source extracted confidence: high 2026-04-09
#humans #randomized-controlled-trials-as-topic #proton-pump-inhibitors #gastroesophageal-reflux #heartburn

A systematic review and meta-analysis of randomized controlled trials: the role of potassium-competitive acid blockers in endoscopy-negative reflux disease

Koo et al., 2025 | Dig Liver Dis | Meta Analysis

Citation

Koo Thai Hau, Fass Ronnie. A systematic review and meta-analysis of randomized controlled trials: the role of potassium-competitive acid blockers in endoscopy-negative reflux disease. Dig Liver Dis. 2025-Sep;57(9):1752-1760. doi:10.1016/j.dld.2025.04.045

Abstract

BACKGROUND: Although proton-pump inhibitors (PPIs) have long been the mainstay of therapy for endoscopy-negative reflux disease (ENRD), their therapeutic limitations have become apparent. AIM: This study aimed to evaluate the efficacy and safety of potassium-competitive acid blockers (PCABs) compared to PPIs/placebos in treating ENRD. METHODS: Only randomized controlled trials (RCTs) comparing PCABs with PPIs/placebos in ENRD and indexed in MEDLINE, EMBASE, and CENTRAL until May 20, 2024, were included. A random-effects model meta-analysis was performed to pool the primary efficacy outcomes (heartburn resolution and mean heartburn severity at week four) and safety data (any treatment-emergent adverse event or TEAE). The risk of bias was assessed using the Cochrane's Risk of Bias 2 (RoB2) tool. RESULTS: Four RCTs comparing PCABs and placebos with a total of 2387 participants, were included. All the trials had a low risk of bias. Compared with placebos, PCABs significantly increased the likelihood of heartburn resolution (risk ratio[RR]:1.43;95 %CI:1.22-1.68). The severity of heartburn was significantly reduced by PCABs (standardized mean difference[SMD]:0.19;95 %CI:0.35 to -0.02). TEAEs were comparable between the PCABs and placebos (odds ratio[OR]:1.06;95 %CI:0.82-1.37). CONCLUSIONS: PCABs are superior to placebos in enhancing heartburn resolution and reducing heartburn severity in patients with ENRD, and their safety profile is comparable to that of placebos.

Key Findings

Four RCTs comparing PCABs and placebos with a total of 2387 participants, were included. All the trials had a low risk of bias. Compared with placebos, PCABs significantly increased the likelihood of heartburn resolution (risk ratio[RR]:1.43;95 %CI:1.22-1.68). The severity of heartburn was significantly reduced by PCABs (standardized mean difference[SMD]:0.19;95 %CI:0.35 to -0.02). TEAEs were comparable between the PCABs and placebos (odds ratio[OR]:1.06;95 %CI:0.82-1.37).

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population enrd
Sample Size 2387
Age Range See abstract
Condition See abstract

MeSH Terms

  • Humans
  • Randomized Controlled Trials as Topic
  • Proton Pump Inhibitors
  • Gastroesophageal Reflux
  • Heartburn
  • Treatment Outcome

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Systematic Review, Meta-Analysis
  • Vertical: potassium

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09