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

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.