Potassium-competitive Acid Blocker Research Articles

Peroral endoscopic myotomy alone is effective for esophageal motility disorders and esophageal epiphrenic diverticulum: a retrospective single-center study.

Esophageal epiphrenic diverticulum (ED) is associated with esophageal motility disorder (EMD). If a diverticulum associated with EMD is enlarging with worsening symptoms, surgical intervention, including laparoscopic epiphrenic diverticulectomy with myotomy and fundoplication, is indicated. However, some studies suggest that myotomy alone, with less adverse events, is sufficient to improve symptoms. Additionally, peroral endoscopic myotomy (POEM) is considered effective and safe for EMD. Since theoretically, POEM is endoscopic Heller myotomy, POEM without diverticulectomy is considered a less invasive, promising treatment option for EMD and ED. We aimed to determine the efficacy and safety of POEM alone for ED with EMD. This single-center study was retrospective. A total of 298 patients underwent POEM in Kobe University Hospital from April 2015 to October 2018. Of them, 14 patients had ED. Procedure-related outcomes and treatment outcomes 3months post POEM were evaluated in these patients. The median maximum ED diameter was 29 (range 9-90) mm; and the median POEM procedure time, 77.5 (range 41-123) min. Pneumoperitoneum, which required needle decompression, occurred in one patient, but no fatal adverse events occurred. The median Eckardt score significantly decreased from 5 [range 2-11] pre POEM to 0 [range 0-2] post POEM (P < 0.0001). The median integrated relaxation pressure significantly decreased from 22.5 [13.9-34.3] mmHg pre POEM to 10.2 [0.7-23.9] mmHg post POEM (P < 0.0001). Of 14 patients, only one patient complained of gastroesophageal reflux disease symptoms, which could be controlled with a potassium-competitive acid blocker. POEM alone seemed effective and safe for patients with EMD and ED.

Randomised trial of acid inhibition by vonoprazan 10/20 mg once daily vs rabeprazole 10/20 mg twice daily in healthy Japanese volunteers (SAMURAI pH study).

Vonoprazan (V), a potassium-competitive acid blocker, has a more durable acid-inhibitory effect as compared with standard-dose proton pump inhibitors (PPIs) but has not been compared with 2-4 times higher daily PPI doses administered in two divided doses. To evaluate the acid-inhibitory effect of V 10/20mg once-daily (OD; V10/V20) vs rabeprazole (R) 10/20mg twice-daily (BID; R20/R40) in healthy Japanese volunteers. This multicentre, randomised, open-label, two-period, crossover study compared V10 or V20 vs R20, or V20 vs R40 using three cohorts of 10 healthy Japanese adults. Within each cohort, subjects were randomised to receive V or R for 7days and, following a washout period≥7days, the other treatment for 7days. On day 6 of each period, 24-hours multichannel gastric impedance-pH monitoring was performed. Percent times pH≥3, ≥4 and≥5 (pH 3, 4 and 5 holding time ratios [HTRs]) in 24hours were evaluated as primary pharmacodynamic endpoints. Acid-inhibitory effect (24-hours pH 3 HTR) of V20 was greater than those of R20 (91.0% vs 65.3%; P=.0049) and R40 (98.5% vs 85.9%; P=.0073). Similar results were obtained for 24-hours pH 4 and 5 HTRs. V20 also achieved greater nocturnal pH 4 (91.5% vs 73.2%; P=.0319) and 5 HTRs (78.8% vs 62.2%; P=.0325) as compared with R40. One subject (20%) developed diarrhoea while receiving R40 which was considered treatment-related. Compared with 2-4 times the standard daily dose of R, V20 exerts a more potent and durable acid-inhibitory effect. Trial identifier: UMIN000022198 (www.umin.ac.jp/ctr/index.htm).

Effectiveness and Safety of Vonoprazan versus Proton Pump Inhibitors for Second-Line Helicobacter pylori Eradication Therapy: Systematic Review and Meta-Analysis

Background: A novel potassium-competitive acid blocker, vonoprazan (VPZ), improves first-line Helicobacter pylori eradication success. The aim of this systematic review is to clarify the effectiveness and safety of second-line H. pylori eradication therapy comparing VPZ and proton pump inhibitor (PPI)-based regimens. Methods: Medline (PubMed), EMBASE, Web of Science, Cochrane Library, and the Japan Medical Society Database were searched. Results: We selected 16 studies for quantitative review. Forest plot analysis showed significant superiority of VPZ over PPI-based regimens in overall second-line H. pylori eradication success (OR 1.51, 95% CI 1.27–1.81, p < 0.001). Forest plots from 2 studies with propensity score matched analysis showed significant superiority of VPZ over PPI-based regimens (OR 3.09, 95% CI 1.71–5.58, p < 0.001). The remaining 14 studies with per-protocol analysis and the full analysis set also showed significant superiority (OR 1.40, 95% CI 1.16–1.69, p < 0.001). Regarding adverse events, Forest plot analysis did not show a significant difference between the 2 regimens (OR 0.88, 95% CI 0.58–1.32, p = 0.53). Conclusions: A VPZ-based regimen has significant superiority over a PPI-based regimen for second-line H. pylori eradication therapy. A VPZ-based second-line H. pylori eradication regimen can be the first choice.

Feasibility of gastric endoscopic submucosal dissection without using proton pump inhibitor injection: a propensity score analysis.

Purpose: Endoscopic submucosal dissection is a promising method for the resection of superficial gastric neoplasms. To date, several institutions have used proton pump inhibitor injections over the perioperative period. However, there is very little evidence regarding their efficacy. To overcome this limitation, we compared procedural outcomes and the prevention of adverse events of proton pump inhibitor injection with an orally administered active potassium-competitive acid blocker alone.Participants and Methods: We enrolled a total of 150 patients treated for superficial gastric neoplasms at a single institution between April 2015 and December 2018. Patients treated for 2 days with proton pump inhibitor injections following 12 days of oral potassium-competitive acid blocker (proton pump inhibitor group=80) were compared with patients treated for 14 days orally with potassium-competitive acid blocker alone (potassium-competitive acid blocker group=70) using propensity score analysis. We evaluated intragastric pH levels prior to endoscopic submucosal dissection, frequency of intraoperative major bleeding, procedure time, en bloc resection rate, curability, ulcer reduction rate 14 days after endoscopic submucosal dissection, and adverse events (including perforation and postoperative bleeding).Results: Propensity score analysis yielded 43 matched pairs. The comparison demonstrated similar values for the outcomes. For all cases, we observed intragastric pH levels >6.4 prior to endoscopic submucosal dissection. Postoperative bleeding rates were 2.3% (1/43) in the proton pump inhibitor group and 0.0% (0/43) in the potassium-competitive acid blocker group (P=0.315).Conclusions: Oral potassium-competitive acid blocker alone was as effective as proton pump inhibitor injection, with a low incidence of adverse events. Based on these results, proton pump inhibitor injection might be omitted during gastric endoscopic submucosal dissection.

Evaluation of pharmacokinetic interactions between amoxicillin, clarithromycin, and the potassium-competitive acid blocker YH4808 in healthy subjects.

YH4808 is a novel potassium-competitive acid blocker that was developed as a therapeutic agent for gastric acid-related diseases; it may replace proton pump inhibitors, which are widely used in combination with amoxicillin and clarithromycin for Helicobacter pylori eradication. We compared the pharmacokinetic (PK) profiles and safety of amoxicillin, clarithromycin, and YH4808 used as monotherapies or in combination for evaluating potential drug interactions. An open-label, randomized, single-dose, Latin-square (4 × 4) crossover study was conducted in 32 healthy Korean volunteers. Subjects were randomly assigned to one of the 4 treatment sequences that consisted of 4 periods separated by 21-day washout intervals. PK parameters of YH4808, amoxicillin and clarithromycin administered in combination were compared with those of the respective monotherapies. The geometric mean ratios of the maximum concentration (Cmax) and the area under the time-concentration curve from time zero to time of the last quantifiable concentration (AUClast) of YH4808 increased during the triple therapy by 48.6% and 29.1%, respectively. Similarly, the Cmax and AUClast of M3 (active metabolite of YH4808) increased by 23.3% and 16.0%, respectively. The Cmax and AUClast of clarithromycin increased by 27.4% and 30.5%, and those of 14-hydroxyclarithromycin were increased by 23.1% and 32.4%, respectively. The corresponding amoxicillin values decreased during the triple therapy by 21.5% and 15.6%, respectively. There was no clinically significant change in safety assessment related to either monotherapies or triple therapy. In conclusion, amoxicillin, clarithromycin and YH4808 administered as triple therapy did not exhibit significant PK interactions and were not associated with safety issues.Trial RegistrationClinicalTrials.gov Identifier: NCT01921647

Tegoprazan to treat gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is the most common upper gastrointestinal disorder in the United States. Although proton pump inhibitors (PPIs) are the mainstay of therapy for GERD and its complications, they have several limitations, including incomplete symptom resolution. Potassium-competitive acid blockers (P-CABs) were developed to address the limitations of PPIs as well as the need for improved antisecretory effects. Tegoprazan, the newest P-CAB, was approved in 2018 in South Korea for the treatment of erosive esophagitis (EE) and nonerosive reflux disease (NERD). A highly selective inhibitor of the H+/K+-ATPase, tegoprazan is also safe and effective for nocturnal acid breakthrough (NAB) and motility. Further studies of tegoprazan are warranted to define its potential role in the treatment of acid-related disorders.

Pharmacodynamic evaluation of YH4808 for Helicobacter pylori eradication in healthy subjects.

YH4808 is a novel selective potassium-competitive acid blocker demonstrated to be safe and to have inhibitory effects against gastric acid secretion in previous studies. A randomized, open-label, multiple-dose, 3-treatment, 1-period, parallel design study was conducted to compare the Helicobacter pylori eradication rates and acid suppression capacities of three regimens in 60 healthy subjects with H. pylori-positive, and the potential of YH4808 to replace proton-pump inhibitors (PPIs) in standard regimens for H. pylori eradication. Group 1 received YH4808, amoxicillin, and clarithromycin as a novel triple regimen, while Group 2 received YH4808 and amoxicillin only, and Group 3 received esomeprazole, amoxicillin, and clarithromycin, as the standard triple regimen. H. pylori eradication rates were 85.0% for Group 1, 25.0% for Group 2, and 83.3% for Group 3. Relative response rate between Group 1 and 3 was 1.02 (0.50–2.07; 95% CI, χ2 test p = 0.8881). Furthermore, the novel triple regimen, YH4808, amoxicillin, and clarithromycin, stably inhibited acid secretion and maintained a gastric pH greater than 4 or 5 for 24 hours, which was comparable to the pH range in the standard triple regimen. However, the onset times of the YH4808 regimens were earlier than that for the regimens using esomeprazole. There were no differences in the incidences or severity of adverse events among the three groups. Overall, the novel triple regimen was safe and well-tolerated. YH4808 could replace PPIs in standard triple regimens used for H. pylori eradication.Trial RegistrationClinicalTrials.gov Identifier: NCT01921647

Vonoprazan-Based Triple-Therapy Could Improve Efficacy of the Tailored Therapy of Helicobacter pylori Infection.

The prevalence of clarithromycin resistant bacteria is increasing, and the effectiveness of Helicobacter pylori (H. pylori) triple therapy is gradually decreasing in Japan. Vonoprazan, a potassiumcompetitive acid blocker, has been reported for its effectiveness in eradicating H. pylori. We aimed to evaluate the efficacy of tailored vonoprazan-based triple therapy in patients with H. pylori. This study is the first to compare the efficacy of vonoprazan-based tailored triple therapy to that of vonoprazan-based conventional therapy. This retrospective cohort study evaluated the treatment efficacy in 920 patients. Of these, 541 received conventional and 379 received tailored therapy. Successful eradication was confirmed by a negative 13C-urea breath test 6-8 weeks following completion of H. pylori eradication therapy, and the data were evaluated using the Chi-square test, or Fisher's exact test, as appropriate. The eradication rate of tailored therapy was 90% and 96.3% by intent-to-treat analysis and per protocol analysis, respectively, which was significantly higher than the 85% and 90.2% found for conventional therapy (p < 0.05 and p < 0.001, respectively). Amoxicillin- or clarithromycin-resistant bacteria did not affect treatment outcomes. By univariate and multivariate analysis, both amoxicillin- and clarithromycin-resistant bacteria and conventional therapy were detected as risk factors for eradication failure (odds ratio = 6.267, 95% CI [1.056-119.924], p < 0.05, and odd ratio =3.113, 95% confidence interval [1.688-6.160], p < 0.001, by multivariate analysis). Vonoprazan-based triple therapy could be a more effective treatment for H. pylori infection than conventional therapy when combined with a therapy regimen tailored according to bacterial antibiotic susceptibility.

Changes of gastric ulcer bleeding in the metropolitan area of Japan.

BACKGROUNDThe two main causes of gastric ulcer bleeding are Helicobacter pylori (H. pylori) infection and ulcerogenic medicines, although the number of cases caused by each may vary with age. In Japan, the rate of H. pylori infection has fallen over the last decade and the number of prescriptions for non-steroidal anti-inflammatory drugs (NSAIDs) and antithrombotic drugs is increasing as the population ages. Methods of treatment for gastric ulcer bleeding have advanced with the advent of hemostatic forceps and potassium-competitive acid blocker (P-CAB). Thus, causes and treatments for gastric ulcer bleeding have changed over the last decade.AIMTo examine the trends of gastric ulcer bleeding over 10 years in the metropolitan area of Japan.METHODSThis is a single-center retrospective study. A total of 564 patients were enrolled from inpatients admitted to our hospital with gastric ulcer bleeding between 2006 and 2016. Age, medication history, H. pylori infection, method of treatment, rate of rebleeding, and the length of hospitalization were analyzed. Factors associated with gastric ulcer bleeding were evaluated using Fisher’s exact test, Pearson’s Chi-squared test or Student’s t-test as appropriate. The Jonckheere-Terpstra test was used to evaluate trends. A per-protocol analysis was used to examine the rate of H. pylori infection.RESULTSThere was a significant increase in the mean age over time (P < 0.01). The rate of H. pylori infection tended to decrease over the study period (P = 0.10), whereas the proportion of patients taking antithrombotic agents or NSAIDs tended to increase (P = 0.07). Over time, the use of NSAIDs and antithrombotic drugs increased with age. By contrast, the rate of H. pylori infection during the study period fell with age. H. pylori-induced ulcers accounted for the majority of cases in younger patients (< 70 years old); however, the rate decreased with age (P < 0.01). The method of treatment trend has changed significantly over time. The main method of endoscopic hemostasis has changed from clipping and injection to forceps coagulation (P < 0.01), and frequently prescribed medicines have changed from proton pump inhibitor to P-CAB (P < 0.01). The rate of rebleeding during the latter half of the study was significantly lower than that in the first half.CONCLUSIONThese trends, gastric ulcers caused by ulcerogenic drugs were increasing with age and H. pylori-induced ulcers were more common in younger patients, were observed.

The Physiology of the Gastric Parietal Cell.

Parietal cells are responsible for gastric acid secretion, which aids in the digestion of food, absorption of minerals, and control of harmful bacteria. However, a fine balance of activators and inhibitors of parietal cell-mediated acid secretion is required to ensure proper digestion of food, while preventing damage to the gastric and duodenal mucosa. As a result, parietal cell secretion is highly regulated through numerous mechanisms including the vagus nerve, gastrin, histamine, ghrelin, somatostatin, glucagon-like peptide 1, and other agonists and antagonists. The tight regulation of parietal cells ensures the proper secretion of HCl. The H+-K+-ATPase enzyme expressed in parietal cells regulates the exchange of cytoplasmic H+ for extracellular K+. The H+ secreted into the gastric lumen by the H+-K+-ATPase combines with luminal Cl- to form gastric acid, HCl. Inhibition of the H+-K+-ATPase is the most efficacious method of preventing harmful gastric acid secretion. Proton pump inhibitors and potassium competitive acid blockers are widely used therapeutically to inhibit acid secretion. Stimulated delivery of the H+-K+-ATPase to the parietal cell apical surface requires the fusion of intracellular tubulovesicles with the overlying secretory canaliculus, a process that represents the most prominent example of apical membrane recycling. In addition to their unique ability to secrete gastric acid, parietal cells also play an important role in gastric mucosal homeostasis through the secretion of multiple growth factor molecules. The gastric parietal cell therefore plays multiple roles in gastric secretion and protection as well as coordination of physiological repair.

Clinical Characterization of Vonoprazan-Refractory Gastroesophageal Reflux Disease

Introduction: The newly developed vonoprazan (a potassium-competitive acid blocker) has a greater ability to suppress gastric acid production than convention proton pump inhibitors (PPIs). The objective of the present study was to determine how vonoprazan influences the pathogenesis of refractory gastroesophageal reflux disease (GERD) in clinical practice. Methods: Between March 2013 and November 2018, a total of 73 refractory GERD patients (34 in the conventional PPI group versus 39 in the vonoprazan group) were enrolled in this retrospective study. We then compared the underlying disease conditions between the 2 groups, examined by high-resolution manometry and multichannel intraluminal impedance/pH (MII-pH) monitoring. Results: There was a significant difference in the proportion of underlying disease conditions, including erosive esophagitis, non-erosive reflux disease, reflux hypersensitivity, functional heartburn and oesophageal motility disorder (EMD), between the conventional PPI (6, 14, 23, 40 and 17% respectively) and vonoprazan groups (0, 0, 10, 49, and 41% respectively; p < 0.01). No cases of acid-related GERD were observed in the vonoprazan group. When the EMD patients were excluded, the lower oesophageal acid exposure time of the vonoprazan group (0.1% [0.0–0.5%], n = 23) was significantly lower than that of the conventional PPI group (0.35% [0.1–3.9%], n = 28; p < 0.05), and the gastric pH <4 holding time of the vonoprazan group (7.7% [0.7–34.5%]) was also significantly lower than that of the conventional PPI group (61.6% [49.4–74.3%], p < 0.01). Conclusions: Vonoprazan serves as a diagnostic tool to exclude acid-related GERD.

P6405Potential for drug-drug interaction between vonoprazan and prasugrel on antiplatelet effect assessed by VerifyNow P2Y12 assay in patients with coronary artery disease

Abstract Background Vonoprazan is a potassium-competitive acid blocker increasingly used in Japan to prevent gastrointestinal bleeding in patients under dual antiplatelet therapy (DAPT) after coronary stents implantation. Since cytochrome P450 (CYP) 3A4 is involved in the primary metabolism of vonoprazan and prasugurel, there is a possibility that CYP-mediated drug-drug interaction between them can attenuate the antiplatelet function of prasugrel. Purpose The aim of this study was to investigate whether antiplatelet effect of prasugrel could be attenuated upon coadministration with vonoprazan compared to conventional proton pump inhibitors (PPIs). Method We evaluated 72 patients (57 males, 67±11 years) with coronary artery disease who were taking either vonoprazan (n=35) or PPIs (n=37) in combination with DAPT (aspirin and prasugrel) after drug-eluting stents implantation. PPIs included 21 esomeprazole, 8 lansoprazole, and 8 rabeprazole. Antiplatelet effects of prasugrel were assessed using VerifyNow P2Y12 assay. Primary measurements were P2Y12 reaction units (PRU) and P2Y12 percent inhibition. High on-treatment platelet reactivity (HPR) on prasugrel was defined as PRU &gt;208. Administration period of vonoprazan or PPIs in combination with DAPT ≤7 days was defined as early administration period. Results Median administration period of vonoprazan or PPIs in combination with DAPT was 127 days. There were no significant differences in baseline clinical characteristics between patients with vonoprazan and PPIs. In the analysis for all subjects, patients with vonoprazan showed similar PRU (166±50 vs. 167±64, p=0.93) and percent inhibition (36±18 vs. 38±23, p=0.66) compared to those with PPIs. No significant differences were observed in the prevalence of HPR between patients with vonoprazan and PPIs (17 vs. 30%, p=0.27). In the analysis for patients in early administration period [vonoprazan (n=14) vs. PPIs (n=10)], there were no significant differences in PRU (166±47 vs. 186±82, p=0.45), percent inhibition (33±17 vs. 30±26, p=0.73), and prevalence of HPR (14 vs. 50%, p=0.085) between patients with vonoprazan and PPIs. In addition, the analysis for patients over early administration period [vonoprazan (n=21) vs. PPIs (n=27)] showed that PRU (166±55 vs. 160±57, p=0.73), percent inhibition (37±19 vs. 41±21, p=0.57), and prevalence of HPR (19 vs. 22%, p=1.00) were comparable between patients with vonoprazan and PPIs. Conclusion Compared to PPIs, vonoprazan did not exhibit significant inhibitory effects on the antiplatelet activity of prasugrel assessed by VerifyNow assay. These findings suggest that there are possibly no clinically harmful drug-drug interactions between vonoprazan and prasugrel.

The efficacy of vonoprazan for management of post-endoscopic submucosal dissection ulcers compared with proton pump inhibitors: A meta-analysis.

Artificial ulcers after endoscopic submucosal dissection (ESD) are usually treated by proton pump inhibitors (PPIs) in clinical setting. Vonoprazan, a newly developed potassium-competitive acid blocker, has recently been used to treat post-ESD ulcers. We aimed to evaluate the efficacy and safety of vonoprazan on the healing of post-ESD artificial ulcers compared with those of proton pump inhibitors (PPIs) using a meta-analysis. EMBASE, MEDLINE, Scopus and Cochrane Library databases were searched for all studies comparing the efficacy and safety of vonoprazan with those of PPIs in the treatment of post-ESD ulcers. Fourteen articles with 1328 patients were included in this meta-analysis. When comparing ulcer shrinkage rate, vonoprazan showed a better efficacy than PPIs (mean difference 0.56, 95% confidence interval [CI] 0.18-0.93). Vonoprazan also led to a higher scar formation rate (odds ratio [OR] 1.58, 95% CI 1.00-2.47) and showed a potential superiority on reducing the risk of post-ESD bleeding compared with PPIs, with a pooled OR of 0.69, although there was no statistically significant difference. Compared with PPIs, vonoprazan showed a better efficacy in ulcer shrinkage rate and achieved more complete healing in the treatment of post-ESD ulcers. Vonoprazan did not induce any incremental risk of post-ESD bleeding as well. It may be an appropriate choice in the management of artificial ulcers after ESD.

Histamine2-Receptor Antagonists, Proton Pump Inhibitors, or Potassium-Competitive Acid Blockers Preventing Delayed Bleeding After Endoscopic Submucosal Dissection: A Meta-Analysis.

Background: Endoscopic submucosal dissection (ESD) was commonly used for en bloc resection in gastric cancer and adenoma with the risk of delayed bleeding after ESD. We conducted a direct and indirect comparison meta-analysis to evaluate the best choice in preventing post-ESD bleeding among proton pump inhibitors (PPIs), histamine2-receptor antagonists (H2RAs), and the most widely used potassium-competitive acid blocker, vonoprazan. Methods: The Pubmed, Cochrane Library, and Embase were searched for randomized trials. We pooled odds ratios (OR) for preventing post-ESD bleeding using meta-analysis. Results: Sixteen randomized trials met the inclusion criteria including 2,062 patients. Direct comparisons showed slightly significant efficacy in PPIs rather than H2RAs in preventing post-ESD bleeding [OR: 1.83; 95% confidence interval (CI): 1.10 to 3.05] and vonoprazan was better than PPIs (OR: 0.46; 95% CI: 0.25 to 0.86). The adjusted indirect comparison indicated vonoprazan was superior to H2RAs (OR: 0.30, 95% CI: 0.12 to 0.74). In subgroup analysis, PPIs had similar efficacy as H2RAs in 4 weeks, while PPIs were better than H2RAs in 8 weeks’ treatment (OR: 1.91; 95% CI: 1.08 to 3.40). The superiority of vonoprazan than PPIs was more significant in combination therapy (OR: 0.18; 95% CI: 0.04 to 0.69). There was a significant difference in vonoprazan for 8 weeks of medication (OR: 0.44; 95% CI: 0.21 to 0.92). Conclusions: The effects of vonoprazan is better than PPIs than H2RAs in preventing bleeding after ESD. When vonoprazan combined with mucosal protective antiulcer drug in treatment or used in 8 weeks of medication, the efficacy may be even better.

Review: Helicobacter pylori in pediatrics.

Despite a decrease in the prevalence of Helicobacter pylori infection, it still poses a significant health burden worldwide. This review summarizes important pediatric studies on Hpylori published from April 2018 to March 2019. Epidemiologic studies have reported different prevalences in different parts of the world and have mainly confirmed traditional risk factors. Several studies on pathophysiology attempted to identify risk markers in childhood for gastric cancer development later in life. One of the most interesting studies evaluated the relationship between eosinophilic esophagitis and Hpylori infection; however, an inverse relationship was not confirmed. The high resistance of Hpylori and, consequently, low eradication rates, is still a major concern and susceptibility testing before treatment has again been highlighted. Potassium-competitive acid blockers are promising new acid-suppressant drugs but their role in Hpylori eradication schemes is still to be determined.

Dual Therapy with Vonoprazan and Amoxicillin Is as Effective as Triple Therapy with Vonoprazan, Amoxicillin and Clarithromycin for Eradication of Helicobacter pylori

Backgrounds/Aims: Vonoprazan (VPZ) is the first clinically available potassium competitive acid blocker. This class of agents provides faster and more potent acid inhibition than proton pump inhibitors. Most strains of Helicobacter pylori are sensitive to amoxicillin. We hypothesized that dual therapy with VPZ and amoxicillin would provide the sufficient eradication rate for H. pylori infection. To evaluate this, we compared the eradication rate by the dual VPZ/amoxicillin therapy with that by the standard triple VPZ/amoxicillin/clarithromycin therapy. Methods: Non-inferiority of the eradication rate of H. pylori by the dual therapy with VPZ 20 mg twice daily (bid) and amoxicillin 500 mg 3 times daily (tid) for 1 week to that by the triple therapy with VPZ 20 mg bid, amoxicillin 750 mg bid and clarithromycin 200 mg bid for 1 week was retrospectively studied. Propensity score matching was performed to improve comparability between 2 regimen groups. Successful eradication was diagnosed using the [¹³C]-urea breath test at 1–2 months after the end of eradication therapy. Results: The intention-to-treat analysis demonstrated that the eradication rate by the dual therapy (92.9%; 95% CI 82.7–98.0%, 52/56) was not inferior to that of the triple therapy (91.9%; 95% CI 80.4–97.0%, 51/56; OR 1.275, 95% CI 0.324–5.017%, p = 0.728). There were no statistically significant differences in incidences of adverse events between 2 regimens. Conclusion: VPZ-based dual therapy (VPZ 20 mg bid and amoxicillin 500 mg tid for 1 week) provides an acceptable eradication rate of H. pylori infection without the need for second antimicrobial agents, such as clarithromycin.

The potential role of potassium-competitive acid blockers in the treatment of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is primarily a motor disorder, but its pathogenesis is multifactorial. Although gastric acid secretion is usually normal in GERD patients, treatment with proton pump inhibitors (PPIs) has become the standard of care, despite increasing awareness of their shortcomings. In this article, a new class of antisecretory drugs (namely potassium-competitive acid blockers, P-CABs), developed to overcome these limitations, is discussed. P-CABs block the K exchange channel of the proton pump, resulting in rapid, competitive, reversible inhibition of acid secretion. These drugs offer a more rapid elevation of intragastric pH than PPIs, while maintaining similar antisecretory effect, the duration of which is dependent on half-life and can be prolonged with extended release formulations. Thus, P-CABs offer advances in the treatment of GERD including rapid heartburn relief, faster and more reliable healing of severe grades of erosive esophagitis, as a consequence of better control of nighttime acid secretion than PPIs. P-CABs overcome many of the drawbacks of PPIs. The unique antisecretory effects of vonoprazan might be especially useful in the long-term treatment of patients with Barrett's esophagus.

Efficacy of Vonoprazan for Helicobacter pylori Eradication.

Helicobacter pylori can infect the gastric mucosa and cause chronic inflammation, resulting in various diseases, including gastric cancer. Eradication of H. pylori in all infected subjects is recommended; however, the number of H. pylori strains with antibiotic resistance has increased, and the eradication rate has decreased. Vonoprazan, a potassium-competitive acid blocker, produces a stronger acid-inhibitory effect than proton pump inhibitors (PPIs). The H. pylori eradication rate with vonoprazan was found to be higher than that with PPIs. The H. pylori eradication rate with vonoprazan-based triple therapy (vonoprazan, amoxicillin, and clarithromycin) was approximately 90% and had an incidence of adverse events similar to that of PPIs. We review the current situation of H. pylori eradication in Japan, the first country in which vonoprazan was made available.

Current Status of Helicobacter pylori Diagnosis and Eradication Therapy in Japan Using a Nationwide Database

Background: Helicobacter pylori infection increases the risk of stomach cancer; therefore, eradication therapy is recommended for infected individuals. Although several methods are recommended for the diagnosis and therapy of H. pylori infection, their frequency and effectiveness have not been fully investigated in Japan. Methods: A nationwide claims database including >1.6 million patients (April 2008 – ­October 2016) in Japan was utilized. We analyzed the distribution of methods for H. pylori diagnosis and therapy, waiting period between eradication and diagnostic test, and success rate of primary therapy. Results: Data for 481,041 patients were extracted. After primary eradication therapy, urea breath test was used for >80% of diagnoses, and antibody measurement for 0.7%. The success rate of primary eradication was >80% for most diagnostic methods and 69.0% for antibody measurement; inappropriately-timed antibody measurement may have contributed to this disparity. The overall success rate of eradication therapy decreased from 2011 to 2014, but increased from 2015, coinciding with launch of the potassium-competitive acid blocker vonoprazan, which showed a higher success rate of eradication than proton-pump inhibitors. Conclusions: Diagnostic tests of H. pylori infection mostly followed Japanese Society for Helicobacter Research guidance, although some antibody measurements were timed inappropriately. Vonoprazan appears to increase the success rate of primary therapy.

Gastric candidiasis developing after administration of potassium-competitive acid blocker

Gastric candidiasis developing after administration of potassium-competitive acid blocker