Copyright ©The Author(s) 2022.
World J Gastroenterol. Jul 28, 2022; 28(28): 3608-3619
Published online Jul 28, 2022. doi: 10.3748/wjg.v28.i28.3608
Table 1 Main differences in the mechanisms of action between proton pump inhibitors and potassium-competitive acid blockers[12]
Proton pump inhibitors
Potassium-competitive acid blockers
Prodrug requires transformation to the active form, sulphenamideDirect action on the H+/K+ ATPase after protonation
Sulphenamide binds covalently to H+/K+-ATPaseP-CABs bind competitively to the K+ binding site of H+/K+-ATPase
Irreversible binding to the proton pumpReversible binding to the proton pump
The full effect after repeated dosesThe full effect after the first dose
PK affected by genetic polymorphismPK not affected by genetic polymorphism
PD effect more significant during the daytimePD effect lasting for both the daytime and nocturnal hours
Meal-dependent antisecretory activityMeal-independent antisecretory activity
Concentrate in parietal cell acid space (1000-fold higher than in plasma)Super concentrates in parietal cell acid space (100000-fold higher than in plasma)
Duration of effect related to the half-life of the sulphenamide-enzyme complexDuration of effect related to the half-life of the drug in plasma
Table 2 Clinical studies regarding the efficacy of potassium-competitive acid blocker in gastroesophageal reflux disease treatment
Study design
Patients, n
Treatment groups
Duration of treatment, wk
Clinical outcomes
Ashida et al[42]JapanMulticenter, randomized, double-blind732EELPZ 30 mg; VPZ 5 mg; VPZ 10 mg; VPZ 20 mg; VPZ 40 mg8All VPZ regimens were non-inferior to LPZ 30 mg treatment. The proportions of healed EE subjects were 87.3%, 86.4%, 100%, 96.0%, and 87.0% with VPZ 5, 10, 20, 40 mg, and LPZ 30 mg, respectively
Ashida et al[43]JapanMulticenter, randomized, double-blind607EELPZ 15 mg; VPZ 10 mg; VPZ 20 mg24The EE recurrence rates were 16.8%, 5.1%, and 2.0% with LPZ 15 mg, VPZ 10 mg, and VPZ 20 mg, respectively, over the 24-wk maintenance period
Shinozaki et al[47]JapanRetrospective cohort55NERD = 30; EE = 25VPZ 10 mg4The VPZ 10 mg for 1-mo alleviated GERD symptoms in 89% and were sustained in 82% after 1 yr without further therapy
Oshima et al[48]JapanRandomized placebo control32EELPZ 30 mg; VPZ 20 mg2The heartburn was relieved earlier with VPZ than with LPZ, and it was completely relieved in 31.3% and 12.5% of patients on day 1 with VPZ and LPZ, respectively
Akiyama et al[49]JapanRetrospective cohort with prospective study13PPI-refractory GERDPPIs switch to VPZ 20 mg8The median gastric acid exposure times of the VPZ 20 mg were lower than the median gastric acid exposure times of the PPI treatment in both daytime and nocturnal observations. The VPZ 20 mg outperforms PPIs in stomach acid suppression, EAE control, symptom alleviation, and esophagitis healing in patients with PPI-refractory GERD
Mizuno et al[50]JapanOpen-label, single-center, prospective study50PPI-refractory REPPIs switch to VPZ 20 mg for 4 wk and VPZ 10 mg48VPZ 10 mg prevented the recurrence of esophageal mucosal breaks in 43 of 50 (86.0%) patients. VPZ 10 mg is clinically efficacious for the long-term maintenance of healed RE
Xiao et al[51]China, South Korea, Taiwan, MalaysiaPhase III, double-blind, multicenter study481EELPZ 30 mg; VPZ 20 mg8The 8-wk EE healing rates in the VPZ and LPZ groups were 92.4% and 91.3%, respectively. VPZ 20 mg was not inferior to LPZ 30 mg in EE healing at 8 wk
Okanobu et al[52]JapanRandomized control study73EEVPZ 10 mg; VPZ 20 mgEach dose for 4 wk and VPZ 10 mg for 8 wkVPZ 10 mg had the same result as VPZ 20 mg in mucosal healing and symptom reduction at 4 wk and throughout the trial
Matsuda et al[53]JapanMulticenter, randomized, cross-over study122Erosive GERDVPZ 10 mg; LPZ 15 mgEvery 2nd day for 4 wk and cross-over for more 4 wkGERD symptoms were significantly reduced with VPZ 10 mg every other day, as measured by the FSSG and the gastrointestinal symptom rating scale
Lee et al[54]South KoreaRandomized, double-blind, parallel-group comparison study302EETPZ 50 mg; TPZ 100 mg; EPZ 40 mg4 and 8At week 8, the cumulative healing rates for TPZ 50 mg, TPZ 100 mg, and EPZ 40 mg were 98.9%, 98.9%, and 98.9%, respectively
Kim et al[55]South KoreaPhase III, double-blind, placebo-controlled, multicenter study324NERDTPZ 50 mg; TPZ 100 mg; placebo4The proportions of heartburn-free days and full-resolution rates of heartburn were significantly higher in both TPZ groups than in the placebo group
Lee et al[56]South KoreaPhase III, multicenter, randomized, double-blind trial260EEFPZ 40 mg; EPZ 40 mg8FPZ 40 mg was non-inferior to EPZ 40 mg. FPZ 40 mg provided better symptom relief in patients with moderate to severe heartburn, with the effect lasting throughout the night