Comparison of vonoprazan and proton pump inhibitors for the management of gastric post-endoscopic submucosal dissection ulcers and preventing delayed bleeding: a meta-analysis of randomized controlled trials.

BACKGROUND: Delayed bleeding and artificial-ulcer healing are important clinical concerns after gastric endoscopic submucosal dissection (ESD). Vonoprazan rapidly suppresses gastric acid, but its efficacy relative to proton pump inhibitors (PPIs) remains uncertain. METHODS: We searched seven databases from inception to May 31, 2026. Randomized controlled trials (RCTs) comparing vonoprazan with PPIs after gastric ESD were included. Outcomes were pooled as relative risks (RRs) or mean differences (MDs), with 95% confidence intervals (CIs). RESULTS: Eleven RCTs reported delayed-bleeding data for 1,136 participants (580 receiving vonoprazan and 556 receiving a PPI). Delayed bleeding occurred in 16/580 (2.76%) vs. 32/556 (5.76%) participants (RR = 0.51, 95% CI 0.29-0.89; P = 0.02). Nine trials contributed to the relative-effect estimate because two reported zero events in both arms; a risk-difference sensitivity analysis including all 11 trials supported the result. Ulcer healing rates did not differ at 4 weeks (RR = 0.93, 95% CI 0.65-1.33; P = 0.69) or 8 weeks (RR = 0.98, 95% CI 0.92-1.04; P = 0.49). Ulcer shrinkage rates also did not differ at 4 weeks (MD = -0.89, 95% CI -2.10 to 0.33; P = 0.15) or 8 weeks (MD = 0.45, 95% CI -0.27 to 1.16; P = 0.22). Adverse events were less frequent with vonoprazan (RR = 0.57, 95% CI 0.34-0.98; P = 0.04). CONCLUSION: Vonoprazan may reduce delayed bleeding and adverse events after gastric ESD while achieving ulcer healing and shrinkage comparable to PPIs; the bleeding estimate is based on few events and should be interpreted cautiously. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261424595, CRD420261424595.