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Review
. 2025 May 16;4(9):100705.
doi: 10.1016/j.gastha.2025.100705. eCollection 2025.

Comparative Efficacy and Safety of Potassium-Competitive Acid Blocker- and Proton Pump Inhibitor-Based Bismuth Quadruple Therapy for Helicobacter pylori Eradication: A Network Meta-Analysis

Iqbal Taufiqqurrachman  1   2 , Ari Fahrial Syam  3 , Hasan Maulahela  3 , Murdani Abdullah  3   4 , Muhammad Miftahussurur  5   6 , Yoshio Yamaoka  1   5   7   8
Affiliations
Review

Comparative Efficacy and Safety of Potassium-Competitive Acid Blocker- and Proton Pump Inhibitor-Based Bismuth Quadruple Therapy for Helicobacter pylori Eradication: A Network Meta-Analysis

Iqbal Taufiqqurrachman et al. Gastro Hep Adv. .

Abstract

Background and aims: The eradication of Helicobacter pylori (H. pylori) reduces the incidence of gastric cancer. However, the efficacy of the widely used triple therapy for eradicating H. pylori has progressively reduced. This may have resulted from the increase in clarithromycin resistance in recent years. Recent guidelines recommend the use of bismuth quadruple therapy (BQT) as first-line eradication therapy for H. pylori infection in areas with high (>15%) or unknown clarithromycin resistance. However, the eradication rates of proton pump inhibitor (PPI)-based BQT remain below the required standard. This systematic review aimed to evaluate the use of novel acid suppressant (potassium-competitive acid blocker [P-CAB])-based BQT compared with PPI-based BQT for H. pylori eradication.

Methods: A systematic review and network meta-analysis were conducted using the PubMed, Cochrane Library, ProQuest, and Scopus databases, along with randomized controlled trials comparing P-CAB-based and PPI-based BQT for H. pylori eradication.

Results: Intention-to-treat analysis showed a pooled risk ratio (RR) of 1.04 (95% confidence interval: 1.02-1.06, I2 = 0) and per-protocol set analysis yielded an RR of 1.04 (95% confidence interval: 1.01-1.07, I2 = 0), favoring P-CAB-based BQT with minimal heterogeneity. Seven studies (n = 2222) reported no significant difference in adverse events (RR: 1.06 [0.99-1.14, I2 = 30.6%]).

Conclusion: Meta-analysis showed the P-CAB-based BQT had slightly higher efficacy than PPI-based BQT. However, network meta-analysis revealed that vonoprazan-based BQT did not show superiority over esomeprazole-based BQT. Therefore, tailored therapies based on local resistance patterns remain critical considerations in clinical practice.

Keywords: Bismuth quadruple therapy; Esomeprazole; Helicobacter pylori; Tegoprazan; Vonoprazan.

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Figures

None
Graphical abstract
Figure 1
Figure 1
Individual Forest Plot of ITT and PPS of P-CAB-based (Experimental) vs PPI-based BQT (Control) as the First Line H. pylori Eradication Therapy. (A) The Forest Plot of ITT Eradication Rate P-CAB vs PPI-based BQT as First Line of H. pylori Eradication Regimens. (B) The Forest Plot of PPS Eradication Rate P-CAB vs PPI-based BQT as First Line of H. pylori Eradication Regimens. Experimental = P-CAB-based BQT; Control = PPI-based BQT.
Figure 2
Figure 2
Forest plot of pairwise comparison of network meta analysis.
Figure 3
Figure 3
Forest Plot of Comparison of Safety between P-CAB-based vs PPI-based BQT as the First Line H. pylori Eradication Therapy. Experimental = P-CAB-based BQT; Control = PPI-based BQT.
Figure S1
Figure S1
Figure S2
Figure S2
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