OBJECTIVE: Previous studies showed that long-term use of proton pump inhibitors (PPIs) was associated with cardiovascular events. However, the impact of short-term PPI exposure on intensive care unit (ICU) patients with myocardial infarction (MI) remains largely unknown. This study aims to determine the precise correlation between short-term PPI usage during hospitalization and prognostic outcomes of ICU-admitted MI patients using Medical Information Mart for Intensive Care IV database (MIMIC-IV).
METHODS: Propensity score matching (PSM) was applied to adjust confounding factors. The primary study outcome was rehospitalization with mortality and length of stay as secondary outcomes. Binary logistic, multivariable Cox, and linear regression analyses were employed to estimate the impact of short-term PPI exposure on ICU-admitted MI patients.
RESULTS: A total of 7249 patients were included, involving 3628 PPI users and 3621 non-PPI users. After PSM, 2687 pairs of patients were matched. The results demonstrated a significant association between PPI exposure and increased risk of rehospitalization for MI in both univariate and multivariate [odds ratio (OR) = 1.157, 95% confidence interval (CI) 1.020-1.313] analyses through logistic regression after PSM. Furthermore, this risk was also observed in patients using PPIs > 7 days, despite decreased risk of all-cause mortality among these patients. It was also found that pantoprazole increased the risk of rehospitalization, whereas omeprazole did not.
CONCLUSIONS: Short-term PPI usage during hospitalization was still associated with higher risk of rehospitalization for MI in ICU-admitted MI patients. Furthermore, omeprazole might be superior to pantoprazole regarding the risk of rehospitalization in ICU-admitted MI patients.

Cisplatin is the most commonly used platinum-based treatment for nasopharyngeal carcinoma (NPC). However, its clinical application is limited owing to its nephrotoxicity and gastrointestinal reactions. Proton pump inhibitors (PPIs) have been reported to increase nephrotoxicity risk in previous studies. We aimed to evaluate whether PPIs increase cisplatin-induced nephrotoxicity in patients with NPC. In total, 295 patients were included in this prospective cohort study: 145 in the PPIs group and 150 in the non-PPIs group. All patients underwent cisplatin-based induction chemotherapy, followed by cisplatin-based concurrent chemoradiotherapy. The PPIs group received 40 mg of intravenous esomeprazole sodium for 7 days in each chemotherapy cycle. Chi-squared test and logistic regression analyses with odds ratios and 95% confidence intervals were applied to assess the association between PPIs and the risk of acute kidney injury (AKI). AKI incidence in the PPIs group was significantly higher than that in the non-PPIs group (P = 0.005). After adjusting for various confounders including demographic features, clinical features, and renal function indices, PPIs use was significantly associated with a higher AKI risk (odds ratio: 2.775; 95% confidence interval 1.280-6.020; P = 0.010). The incidences of acute and chronic kidney diseases were similar between both groups (P > 0.05), whereas the incidence of nausea was lower in the PPIs group than in the non-PPIs group (P = 0.029). This study has shown that PPIs use may increase the risk of cisplatin-induced acute nephrotoxicity in patients with NPC.

Anaprazole is a proton pump inhibitor. This study aims to elucidate absorption, metabolism, and excretion pathways of anaprazole sodium in the human body. A total of 4 healthy Chinese male subjects were administered a single oral dose of 20 mg/100 µCi of [14C]-anaprazole sodium enteric-coated capsules. The whole blood, plasma, and excreta were analyzed for a total radioactivity (TRA) and metabolite profile. The cumulative radioactivity excretion rate was 93.2%, with 53.3% and 39.9% of the radioactive dose excreted in urine and feces, respectively, and 91.6% of dose recovered within 96 hours after dosing. The parent drug, anaprazole, showed good absorption and was extensively metabolized majorly to thioether M8-1 via nonenzymatic metabolism. Overall, 35 metabolites were identified in plasma, urine, and fecal samples. Anaprazole was the most abundant component in plasma followed by the thioether M8-1, accounting for 28.3% and 16.6%, respectively, of the plasma TRA. Thioether carboxylic acid XZP-3409 (26.3% of urine TRA) and XZP-3409 oxidation and dehydrogenation product M417a (15.1% of fecal TRA) were the major metabolites present in urine and feces, respectively. Anaprazole was undetectable in urine, while fecal samples showed traces (0.07% dose). Blood/plasma ratios of the radioactivity (approximately 0.60) remained consistent over time. Anaprazole showed good absorption and was extensively metabolized majorly to thioether M8-1 via nonenzymatic metabolism, and cytochrome P450 3A4 also contributed to its metabolism in healthy individuals.

UNASSIGNED: Acute kidney injury (AKI) is a severe postoperative complication in patients undergoing major surgery. Proton pump inhibitors (PPIs) are used preoperatively as prophylaxis for postoperative gastrointestinal bleeding. Whether preoperative PPI use is associated with an increased risk of postoperative AKI remains uncertain.
UNASSIGNED: This retrospective cohort study used electronic medical records from the clinical data warehouse of Peking University First Hospital to screen all adult hospitalizations undergoing major surgery between 1 January 2018 and 31 December 2020. Exposure was preoperative PPI use, defined as PPI use within 7 days before major surgery. The primary outcome was postoperative AKI, defined as AKI occurring within 7 days after major surgery; secondary outcomes included in-hospital AKI and in-hospital mortality.
UNASSIGNED: A total of 21,533 patients were included in the study (mean [SD] age, 57.8 [15.0] years; 51.2% male), of which 944 (4.4%) were prescribed PPI within 7 days before major surgery (PPI users). Overall, 72 PPI users (7.6%) and 356 non-users (1.7%) developed postoperative AKI. After adjustment, preoperative PPI use was associated with an increased risk of postoperative AKI (adjusted OR, 1.47; 95% CI, 1.04-2.07) and in-hospital AKI (adjusted OR, 1.41; 95% CI, 1.03-1.94). Moreover, subgroup analyses showed that the risk of PPI on postoperative AKI was amplified by the concomitant use of non-steroidal anti-inflammatory drugs or diuretics. No significant difference was observed between preoperative PPI use and in-hospital mortality in the fully adjusted model (adjusted OR 1.63; 95% CI, 0.55-4.85).
UNASSIGNED: Preoperative PPI use was associated with an increased risk of AKI in patients undergoing major surgery. This risk may be enhanced by the concomitant use of other nephrotoxic drugs. Clinicians should weigh the pros and cons before initiating PPI prophylaxis.

BACKGROUND: Current guidelines recommend bismuth-containing quadruple therapy for patients newly diagnosed with Helicobacter pylori (H. pylori) infection. We aimed to compare the efficacy and safety of tetracycline administered three times daily versus four times daily in bismuth-containing quadruple therapy for first-line treatment of H. pylori infection.
METHODS: This multicenter, noninferiority, randomized controlled study, conducted in China, recruited treatment-naïve adults with H. pylori infection, randomized 1:1 into two treatment groups to receive either of the following bismuth-containing quadruple therapies: esomeprazole 20 mg twice-daily; bismuth 220 mg twice-daily; amoxicillin 1000 mg twice-daily; and tetracycline 500 mg three times daily (TET-T) versus 500 mg four times daily (TET-F). At least 6 weeks post-treatment, a 13C-urea breath test was performed to evaluate H. pylori eradication.
RESULTS: In total, 406 patients were randomly assigned to the two treatment groups. Intention-to-treat eradication rates were 91.63% (186/203; 95% confidence interval [CI] 87.82%-95.44%) versus 90.15% (183/203; 95% CI 86.05%-94.25%) (p = 0.0005) and per-protocol eradication rates were 95.34% (184/193; 95% CI 92.36%-98.31%) versus 95.72% (179/187; 95% CI 92.82%-98.62%) (p = 0.0002) for the TET-T and TET-F group, respectively. TET-T-treated patients had a lower incidence of adverse effects than TET-F-treated patients (21.61% vs. 31.63%, p = 0.024), with no significant differences in compliance to treatment between the groups.
CONCLUSIONS: As a first-line therapy for H. pylori infection, the eradication rate of the TET-T therapy was noninferior to that of the TET-F therapy while significantly reducing the incidence of adverse reactions.
BACKGROUND: ClinicalTrials.gov identifier: NCT05431075.

UNASSIGNED: Prolonged or excessive use of acid suppressants may increase the risk of Clostridioides difficile infection (CDI) by altering the intestinal microecosystem. Vonoprazan, a novel potassium-competitive acid blocker, exhibits a faster and more sustained acid-suppressive effect than proton pump inhibitors (PPIs). Therefore, vonoprazan may have a greater impact on the gut microbiota, potentially resulting in CDI.
UNASSIGNED: This study aimed to explore the potential relationship between acid suppressants and CDI by the Japan Adverse Drug Event Report (JADER) and the FDA Adverse Event Reporting System (FAERS) databases.
UNASSIGNED: A retrospective analysis of the JADER and FAERS databases was examined by disproportionality analysis.
UNASSIGNED: We performed signal detection analyses of CDI induced by vonoprazan and PPIs using the JADER and FAERS databases. The association between acid suppressants and CDI was calculated using the reporting odds ratio (ROR) and corresponding 95% confidence interval (95% CI). When the lower limit of the 95% CI is exceeded by 1, the association is considered statistically significant.
UNASSIGNED: In the JADER database, the ROR (95% CI) for vonoprazan and PPIs based on suspect drug reports was 15.84 (12.23-20.50) and 2.51 (1.92-3.28), respectively. In the FAERS database, the ROR (95% CI) for vonoprazan and PPIs based on primary and secondary suspect drug reports was 11.50 (6.36-20.82) and 1.42 (1.34-1.51), respectively. Subgroup analysis showed that elderly patients aged 60 years and older were more strongly associated with CDI. The ROR (95% CI) for vonoprazan and PPIs in patients aged 60 years and older in the JADER database was 15.35 (11.59-20.33) and 1.65 (1.14-2.39), respectively. Similarly, the ROR (95% CI) for vonoprazan and PPIs in the FAERS database was 12.56 (6.26-25.20) and 1.43 (1.31-1.57), respectively. Excluding the effect of Helicobacter pylori (H. pylori) infection, the use of acid suppressants was still associated with CDI.
UNASSIGNED: While signal detection analysis based on the JADER and FAERS databases could not establish causality, our study demonstrated that both vonoprazan and PPIs were significantly associated with CDI. Vonoprazan showed a stronger association with CDI in both databases.
Vonoprazan and Clostridioides difficile infection risk.
UNASSIGNED: Vonoprazan is a new type of acid suppressant, which has a stronger effect on acid inhibition than traditional proton pump inhibitors (PPIs). Vonoprazan may have a greater impact on the gut microbiota, which may increase the risk of Clostridioides difficile infection (CDI). The FDA created the FDA Adverse Event Reporting System (FAERS) database to support the post-market surveillance program. The PMDA created the Japan Adverse Drug Reaction Event Report (JADER) database to specifically collect adverse reaction reports in Japan. To further understand the potential relationship between acid suppressants and CDI, this study was analyzed using the JADER and FAERS databases.
UNASSIGNED: This study analyzed cases of CDI reported after the use of acid suppressants in the JADER and FAERS databases.
UNASSIGNED: The analysis revealed that vonoprazan and PPIs are significantly associated with CDI in both databases. Notably, vonoprazan exhibited a stronger association compared to PPIs. Subgroup analysis indicated that this association was more pronounced in elderly patients aged 60 years and older. Additionally, excluding the influence of Helicobacter pylori (H. pylori) did not diminish the association between acid suppressants and CDI.
UNASSIGNED: Although signal detection analysis based on the JADER and FAERS databases could not establish causality, the results showed that both vonoprazan and PPIs were significantly associated with CDI. Vonoprazan was also more strongly associated with CDI than PPIs, which could be a potential safety concern, and further clinical studies are needed to confirm this finding.

BACKGROUND: The effect of preprandial or postprandial administration of amoxicillin on the efficacy of vonoprazan-amoxicillin dual therapy (VA-dual therapy) for Helicobacter pylori treatment has not been studied. It is also unclear whether amoxicillin dosing four times daily is more effective than three times daily. We aimed to investigate the effect of different amoxicillin administration regimens on the efficacy of VA-dual therapy.
METHODS: H. pylori-infected subjects were randomly assigned to three groups in a 1:1:1 ratio to receive a 14-day dual therapy consisting of vonoprazan 20 mg twice daily + amoxicillin 1000 mg three times daily before meals (BM-TID) or 1000 mg three times daily after meals (AM-TID) or 750 mg four times daily after meals (AM-QID). H. pylori eradication rates, adverse events rates, compliance, and antibiotic resistance were compared.
RESULTS: Between May 2021 to April 2023, 327 subjects were enrolled. The eradication rates of BM-TID, AM-TID, and AM-QID dual therapy were 88.1%, 89.9%, and 93.6% in intention-to-treat (ITT) analysis, 90.6%, 94.2%, and 99.0% in modified ITT (MITT) analysis, and 90.4%, 94.1%, and 99.0% in per-protocol (PP) analysis. Although there was non-inferiority between BM-TID and AM-TID, as well as between AM-TID and AM-QID, AM-QID was significantly more effective than BM-TID. There were no significant differences in adverse event rates, compliance, and antibiotic resistance among the three groups.
CONCLUSIONS: Postprandial administration and the increased frequency of administration of amoxicillin may contribute to a better efficacy of VA-dual therapy, especially for rescue therapy. All VA-dual therapy in our study could achieve good efficacy for first-line treatment.
BACKGROUND: clinicaltrials.gov: NCT05901051.

BACKGROUND: The efficacy of Vonoprazan-amoxicillin dual therapy (VAT) in the treatment of Helicobacter pylori (H. pylori) is controversial.
OBJECTIVE: To evaluate the efficacy of VAT in the Chinese population.
METHODS: This prospective, multicenter, randomized, open-label, and two-stage study was conducted at 23 centers in Fujian, China (May 2021-April 2022). H. pylori-infected patients were randomized to bismuth quadruple therapy (BQT), BQT-Vonoprazan (BQT-V), seven-day VAT (VAT-7), ten-day VAT (VAT-10), and fourteen-day VAT (VAT-14) groups. The primary endpoint was the H. pylori eradication rate. The secondary endpoint was the frequency of adverse events. This study was registered with the Chinese Clinical Trial Registry, ChiCTR2100045778.
RESULTS: In the first stage, VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated. In the second stage, the eradication rates for BQT, VAT-10, and VA-14 were 80.2% [95% confidence interval (95%CI): 71.4%-86.8%], 93.2% (86.6%-96.7%), 92.2% (85.3%-96.0%) in the intention-to-treat (ITT) analysis, and 80.9% (95%CI: 71.7%-87.5%), 94.0% (87.5%-97.2%), and 93.9% (87.4%-97.2%) in the per-protocol analysis. The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group (P = 0.022 and P = 0.046, respectively). The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group (25.27% and 13.73% vs 37.62%, respectively; P < 0.001).
CONCLUSIONS: VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT, with a more tolerable safety profile in H. pylori-infected patients in Fujian.

BACKGROUND: Vonoprazan, a potassium-competitive acid blocker, is superior to traditional proton pump inhibitor (PPI) in acid suppression and has been approved in the treatment of acid-related disorders. Accumulating evidence suggest associations between PPI use and gut microbiota, yet the effect of vonoprazan on GI microbiota is obscure.
METHODS: Transgenic FVB/N insulin-gastrin (INS-GAS) mice as a model of gastric cancer (GC) were administered vonoprazan by gavage every other day for 12 weeks. Stomachs were evaluated by histopathology, Ki-67 proliferation index, and inflammatory cytokines. The mucosal and lumen microbiota from stomach, jejunum, ileum, cecum, and feces were detected using 16S rRNA gene sequencing.
RESULTS: Higher incidence of intestinal metaplasia and epithelial proliferation were observed in the vonoprazan group than that in the control mice. Vonoprazan also elevated the gastric expression of proinflammatory cytokines, including TNF-α, IL-1β, and IL-6. Each mice comprised a unique microbiota composition that was consistent across different niches. The structure of GI microbiota changed dramatically after vonoprazan treatment with the stomach being the most disturbed segment. Vonoprazan administration shifted the gut microbiota toward the enrichment of pathogenic Streptococcus, Staphylococcus, Bilophila, and the loss of commensal Prevotella, Bifidobacterium, and Faecalibacterium. Interestingly, compared to the controls, microbial interactions were weaker in the stomach while stronger in the jejunum of the vonoprazan group.
CONCLUSIONS: Long-term vonoprazan treatment promoted gastric lesions in male INS-GAS mice, with the disequilibrium of GI microbiome. The clinical application of vonoprazan needs to be judicious particularly among those with high risk of GC.

Helicobacter pylori eradication is crucial in the treatment of peptic ulcers caused by H. pylori infection, a disease highly prevalent in Asia. We present a pooled analysis of two randomized, double-blind, double-dummy, phase 3 studies evaluating the efficacy and safety of vonoprazan-based bismuth-containing quadruple therapy for H. pylori eradication. Patients aged ≥18 years with endoscopically confirmed duodenal or gastric ulcers were randomized 1 : 1 to receive vonoprazan 20 mg or lansoprazole 30 mg once daily for up to 6 (duodenal ulcers) or 8 weeks (gastric ulcers). H. pylori-positive patients received vonoprazan- or lansoprazole-based bismuth-containing quadruple therapy for the first 2 weeks. H. pylori eradication was determined using the carbon-13 urea breath test at a follow-up visit 4 weeks post-treatment. The H. pylori eradication rate was 90.6% with vonoprazan vs. 85.2% with lansoprazole (difference: 5.4%; 95% confidence interval (CI): -0.1, 10.8). H. pylori eradication rates were 7.1% (95% CI: 1.4, 12.8) and 12.6% (95% CI: 3.9, 22.0) higher in patients aged <65 years and current smokers, respectively, with vonoprazan vs. lansoprazole. In the Chinese subpopulation, the H. pylori eradication rate was 92.0% with vonoprazan vs. 86.0% with lansoprazole (difference: 6.1%; 95% CI: 0.5, 11.7). Treatment-emergent adverse events occurred in 72.7 vs. 62.6% of H. pylori-positive patients at baseline in the vonoprazan vs. lansoprazole arm. H. pylori eradication with vonoprazan-based quadruple therapy was noninferior to lansoprazole-based quadruple therapy and exceeded 90%, a clinically relevant threshold for determining the efficacy of H. pylori eradication regimens (ClinicalTrials.gov identifier: NCT03050359; NCT03050307).