Safety and Efficacy of Potassium Competitive Acid Blockers (3 Studies)

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J Arai et al. Clin Gastroenterol Hepatol 2024; 22: 1217-1225.Association Between Vonoprazan and the Risk of Gastric Cancer After Helicobacter pylori Eradication

Methods: Using a population-based claims database in Japan, the authors identified patients who were prescribed a clarithromycin-based first regimen of Hp eradication between 2015 and 2018.

Key findings:

  • Among 54,055 patients, 568 (1.05%) developed gastric cancer (GC) during the follow-up period (mean, 3.65 years).
  • The cumulative incidence of GC was 1.64% at 3 years, 2.02% at 4 years, and 2.36% at 5 years in potassium-competitive acid blocker (PCAB) users and 0.71% at 3 years, 1.04% at 4 years, and 1.22% at 5 years in H2RA users. 
  • Limitations: retrospective study with issues of selection bias and confounding.

In the discussion, the authors note PCABs are being used not only for Hp eradication but for peptic ulcers, reflux and several abdominal symptoms. “According to the results of our study, longer use of PCABs was particularly associated with the increased risk of GC after Hp eradication…it might be better to switch strong acid inhibitors including PCABs ad PPIs to H2RAs before reaching a lengthy prescription period (eg. more than 3 years).”

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X Peng et al. Clin Gastroenterol Hepatol 2024; 22: 1210-1216. Open Access! Efficacy and Safety of Vonoprazan-Amoxicillin Dual Regimen With Varying Dose and Duration for Helicobacter pylori Eradication: A Multicenter, Prospective, Randomized Study

This multicenter, prospective, randomized controlled, noninferiority trial enrolled patients (n=516) with treatment naive H pylori infection from 5 clinical centers. All patients received vonoprazan at 20 mg 2/day. The high dose amoxicillin was 750 mg 4/day and the low dose 1000 mg 2/day.

Key findings:

  • The high-dose amoxicillin combination with vonoprazan regimen, for either 10 or 14 days, was effective and safe in eradicating H pylori, whereas the low-dose amoxicillin regimen for 10 days was less effective. The high-dose per protocol eradication rates were 90.9% vs 94.5 for 10 vs 14 days compared to 82.0% in the low-dose per protocol eradication rate (for 14 days).

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Q Zhuang et al Am J Gastroenterol 2024; 119(5):p 803-813, May 2024. Open Access! Comparative Efficacy of P-CAB vs Proton Pump Inhibitors for Grade C/D Esophagitis: A Systematic Review and Network Meta-analysis. (see prior post: Improved Efficacy with Vonoprazan for Severe Esophagitis). This maintenance treatment group mainly included PPI patients receiving a relatively low once-daily dose (e.g. omeprazole 20mg, lansoprazole 15 mg and esomeprazole 20 mg). Treatment failure rates noted below:

My take: These studies indicate that PCABs are more effective at healing erosive esophagitis as well as H pylori gastritis. However, particularly in patients with Hp infection, the use of PCABs is associated with an increased risk of gastric cancer. The exact long-term risk of strong acid inhibition is unclear, especially in those without a history of Hp infection.

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