Efficacy and Safety of Vonoprazan in Dual/Triple/Quadruple Regimens Both in First‐Line and Rescue Therapy for Helicobacter pylori Eradication: A Systematic Review With Meta‐Analysis

ABSTRACT Background The efficacy of Helicobacter pylori ( H. pylori ) eradication therapies encompassing one or more antibiotics and a proton pump inhibitor (PPI) has lately decreased. Vonoprazan (VPZ), a potassium‐competitive acid blocker, provides higher gastric acid suppression than PPIs. We performed a meta‐analysis evaluating the efficacy and safety of VPZ in H. pylori eradication therapies. Methods Studies were searched in PubMed, Embase, and the Cochrane Library up to June 2023. Efficacy was evaluated by intention‐to‐treat analysis. Data were combined by meta‐analyzing risk differences (RD). Heterogeneity was evaluated by subgrouping. Results Seventy‐seven studies (24 randomized clinical trials) evaluated 44,162 patients (22,297 receiving VPZ and 21,865 PPIs). Overall VPZ efficacy was 88% (95% CI = 87%–90%): 86%, 88%, and 94% for dual/triple/quadruple‐VPZ‐containing therapies. VPZ efficacy was 87% (86%–89%) in first‐line and 90% (87%–93%) in rescue therapy. VPZ performed better than PPIs in treatment‐naïve patients (87% vs. 70%; RD = 0.13, 95% CI = 0.11–0.15) and when using triple regimens. No significant differences were observed in rescue and quadruple therapies. In patients with clarithromycin‐resistant infection, VPZ‐based therapies demonstrated an 81% efficacy (76%–85%), surpassing PPIs (76% vs. 40%; RD = 0.33, 95% CI = 0.24–0.43). For clarithromycin‐susceptible strains, VPZ efficacy was 92% (89%–95%), similar to PPIs. VPZ adverse events rate was 19% (16%–21%), comparable to PPI‐based regimens (18% vs. 13%, respectively; RD = 0.00, 95% CI = −0.01 to 0.02, p = 0.57). Conclusions The efficacy of VPZ‐based regimens was over 85% in all treatment combinations. In treatment‐naïve and clarithromycin‐resistant patients, VPZ performed better than PPIs. In rescue therapy, in clarithromycin‐susceptible patients or when quadruple regimens were prescribed, this advantage was not confirmed. Tolerability was similar in both regimens.