Vonoprazan is not superior to PPIs for healing or preventing gastric/duodenal ulcers; efficacy and safety are comparable.
Background
Vonoprazan, a potassium-competitive acid blocker (PCAB), provides rapid, potent acid suppression and outperforms PPIs in Helicobacter pylori eradication and erosive esophagitis. Its benefit over PPIs for gastric and/or duodenal ulcer healing and prevention has been uncertain. This systematic review and meta-analysis pooled randomized controlled trials (RCTs) comparing vonoprazan to PPIs for ulcer treatment and NSAID/aspirin-associated ulcer prevention.
Patients
- Total RCTs: 15 (43 reports)
- Treatment cohorts: 2,646 adults with gastric and/or duodenal ulcers (including post-ESD, peptic, gastric-only, duodenal-only)
- Prevention cohorts: 1,263 adults with prior ulcers requiring ongoing NSAIDs and/or low-dose aspirin
- Setting: Predominantly Asia (mostly Japan; also China, South Korea, Taiwan, Philippines)
- H. pylori positivity: ~15–85% across studies
Intervention
- Treatment: Vonoprazan 20 mg once daily (some post-ESD trials co-administered rebamipide)
- Prevention: Vonoprazan 10 mg or 20 mg once daily
Control
- Treatment: Standard-dose PPIs (e.g., lansoprazole 30 mg, esomeprazole 20 mg, rabeprazole 10 mg daily)
- Prevention: Lansoprazole 15 mg daily
Outcome
- Primary (treatment): Ulcer healing at Weeks 2, 4, 6, and 8
- Primary (prevention): Ulcer recurrence at Week 24 in NSAID/aspirin users
- Secondary: Ulcer shrinkage (Weeks 4 and 8), any adverse events (AEs), serious AEs (SAEs), delayed bleeding and perforation (post-ESD)
Study Design
- Systematic review and random-effects meta-analysis of RCTs (PROSPERO CRD42023429959; PRISMA-guided)
- Risk of bias: Cochrane RoB2
- Certainty: GRADE (low to moderate overall)
Level of Evidence
Level I: Systematic review and meta-analysis of randomized controlled trials (overall certainty low–moderate).
Follow up period
- Treatment: 2–8 weeks (healing assessed at Weeks 2, 4, 6, 8)
- Prevention: Week 24 primary recurrence outcome (some extensions to 104 weeks)
Results
Primary outcomes
- Ulcer healing (vonoprazan 20 mg vs PPI):
- Week 2: RR 1.02 (95% CI 0.89–1.16)
- Week 4: RR 0.99 (95% CI 0.95–1.04)
- Week 6 (duodenal): RR 1.00 (95% CI 0.96–1.03)
- Week 8: RR 0.99 (95% CI 0.95–1.03)
Interpretation: No difference across time points or ulcer subtypes. NNT: Not applicable/estimable (no absolute difference reported).
- Ulcer recurrence at Week 24 in NSAID/aspirin users:
- Vonoprazan 10 mg vs PPI: RR 0.48 (95% CI 0.18–1.27)
- Vonoprazan 20 mg vs PPI: RR 0.60 (95% CI 0.28–1.30)
Interpretation: No significant reduction in recurrence. NNT: Not estimable without baseline event rates; effect not statistically different from control.
Secondary outcomes
- Ulcer shrinkage (post-ESD):
- Week 4: MD 0.53% (95% CI −0.70 to 1.76)
- Week 8: MD 0.04% (95% CI −0.12 to 0.20)
Interpretation: No meaningful difference.
- Any AEs: RR 1.28 (95% CI 0.82–1.98) — similar between groups
- Serious AEs: RR 1.40 (95% CI 0.69–2.84) — similar between groups
- Delayed bleeding (post-ESD): RR 0.51 (95% CI 0.26–1.00) — trend toward reduction with vonoprazan; not clearly significant
- Perforation (post-ESD): RR 1.67 (95% CI 0.60–4.64) — no difference
Limitations
- Majority of trials conducted in Asia (mostly Japan), limiting generalizability.
- Several post-ESD RCTs had high risk of bias (non-blinded; deviations from intended interventions).
- Limited number of recurrence-prevention trials; imprecision due to small event counts.
- Heterogeneity in ulcer types and co-therapies (e.g., rebamipide use in some studies).
- Findings specific to vonoprazan; not generalizable to other PCABs.
Funding
No funding was obtained for this study.
Citation
Simadibrata DM, Lesmana E, Pratama MIA, Sugiharta AJ, Kalaij AGI, Fadhilla ADD, Danpanichkul P, Syam AF, Simadibrata M. Vonoprazan vs. Proton Pump Inhibitors for Treatment and Prevention of Gastric and/or Duodenal Ulcers: A Systematic Review with Meta-Analysis. Digestive Diseases and Sciences. 2024;69:3863–3874. doi:10.1007/s10620-024-08593-5.