Comparative efficacy and pharmacological heterogeneity of individual potassium-competitive acid blockers: A systematic review and network meta-analysis
Abstract
BACKGROUND Vonoprazan consistently demonstrates superior Helicobacter pylori eradication (HPE) rates compared to other potassium-competitive acid blockers (P-CABs), yet the pharmacological basis for this heterogeneity remains unclear. We hypothesized that the acid dissociation constant (pKa) – which determines acid stability and parietal cell accumulation – may explain the differential efficacy among individual P-CABs. AIM To examine whether pKa values predict clinical efficacy of P-CABs for HPE and erosive esophagitis healing. METHODS A systematic review and network meta-analysis were conducted. Randomized controlled trials (RCTs) comparing P-CABs with proton pump inhibitors (PPIs) were identified from core databases (up to January 2026). Risk of bias was assessed using RoB 2.0 and certainty of evidence using GRADE. RESULTS Thirty RCTs (7639 patients) were included for HPE. High-pKa P-CABs (vonoprazan of 9.06, keverprazan of 9.12) achieved 82%-84% eradication in clarithromycin-resistant infections vs 32%-40% with PPIs, while low-pKa P-CAB achieved only 47.8% (not significant vs PPI). For erosive esophagitis (10 RCTs; 4196 patients), high-pKa zastaprazan (9.95) achieved 100% Los Angeles classification grade C/D healing vs 83.3% with esomeprazole, whereas low-pKa P-CABs showed inferior outcomes. Spearman correlation analysis revealed a positive association between pKa and efficacy (ρ = 0.80). However, fexuprazan (pKa of 9.04) showed PPI-equivalent outcomes despite high-pKa,…
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Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 7,639 participants or records.
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