vonoprazan and Gastrointestinal-Hemorrhage

Low-dose aspirin (LDA) administration prevents cerebral infarction and myocardial infarction, but many studies found an association with mucosal injury. Proton-pump inhibitors (PPIs) can prevent gastric and duodenal mucosal damage, but they may exacerbate small-intestinal mucosal injury by altering the microbiota. We aimed to assess the effect of PPIs on the intestinal flora of LDA users.. Thirty-two recruited patients, who received LDA (100 mg/day) but did not take PPIs, were divided into 15 patients additionally receiving esomeprazole (20 mg/day) and 17 patients additionally receiving vonoprazan (10 mg/day). On days 0, 30, 90, and 180, the microbiota of each patient was examined by terminal restriction fragment length polymorphism analysis, and the serum gastrin, hemoglobin, and hematocrit levels were measured.. Additional PPI administration increased the proportion of Lactobacillales in the microbiota of LDA users. This trend was more prevalent in the vonoprazan group (p < 0.0001) than in the esomeprazole group (p = 0.0024). The Lactobacillales proportion was positively correlated with the gastrin level (r = 0.5354). No significant hemoglobin or hematocrit level reduction was observed in subjects receiving LDA with additional PPI.. Additional PPI administration increased the Lactobacillales proportion in the microbiota of LDA users. The positive correlation between the gastrin level and the proportion of Lactobacillales suggested that the change in the intestinal flora was associated with the degree of suppression of gastric acid secretion. Additional oral PPI did not significantly promote anemia, but the risk of causing PPI-induced small-intestinal mucosal injury in LDA users should be considered.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Case-Control Studies; Comorbidity; Dose-Response Relationship, Drug; Esomeprazole; Female; Gastrins; Gastrointestinal Hemorrhage; Gastrointestinal Microbiome; Hematocrit; Hemoglobins; Humans; Intestinal Mucosa; Lactobacillales; Male; Middle Aged; Polymorphism, Restriction Fragment Length; Prospective Studies; Proton Pump Inhibitors; Pyrroles; Sulfonamides

To assess the non-inferiority of vonoprazan to lansoprazole for secondary prevention of non-steroidal anti-inflammatory drug (NSAID)-induced peptic ulcer (PU) and the safety of vonoprazan during extended use.. A phase 3, 24-week, multicenter, randomised, double-blind (DB), active-controlled study, followed by a phase 3, ≥28 week, multicenter, single-blind, parallel-group extension study (EXT) in outpatients (n=642) receiving long-term NSAID therapy who are at risk of PU recurrence. The patients received vonoprazan (10 mg or 20 mg) or lansoprazole 15 mg once daily. For DB, non-inferiority of the proportion of patients with recurrent PU within 24 weeks was analysed by Farrington and Manning test (significance level 2.5%, non-inferiority margin 8.3%; primary endpoint), recurrent PU within 12 weeks, bleeding and time-to-event of PU (secondary endpoint) and treatment-emergent adverse events (TEAEs). For EXT, TEAEs (primary endpoint), recurrent PU and safety (secondary) were assessed up to 104 weeks for patients in the extension study.. The non-inferiority of vonoprazan 10 mg and 20 mg to lansoprazole 15 mg was verified (percentage difference -2.2%,95% CI -6.2% to 1.8%, p<0.001; -2.1%,95% CI -6.1% to 2.0%, p<0.001, respectively). The proportion of patients with endoscopically confirmed recurrent PU within 24 weeks was 3.3%, 3.4% and 5.5%, for vonoprazan 10 mg, 20 mg and lansoprazole 15 mg, respectively. No significant safety concerns were identified.. The non-inferiority of vonoprazan (10 and 20 mg) was verified in patients receiving long-term NSAIDs in DB; it was effective and well tolerated in EXT for longer than 1 year, with a safety profile similar to lansoprazole (15 mg).. NCT01452750, NCT01456260; Results.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Double-Blind Method; Equivalence Trials as Topic; Female; Gastrointestinal Hemorrhage; Humans; Lansoprazole; Male; Middle Aged; Peptic Ulcer; Pyrroles; Recurrence; Secondary Prevention; Single-Blind Method; Sulfonamides; Survival Analysis; Treatment Outcome

Compare efficacy and safety of vonoprazan and lansoprazole for secondary prevention of low-dose aspirin (LDA)-associated peptic ulcers in a 24-week study and long-term extension therapy in separate study.. Double-blind, randomised, non-inferiority study; single-blind extension study at 104 Japanese sites, including 621 patients (439 in extension) with a history of peptic ulcers who required long-term LDA therapy. Randomised (1:1:1, computer generated) patients received lansoprazole 15 mg (n=217), vonoprazan 10 mg (n=202) or vonoprazan 20 mg (n=202) once daily for 24 weeks (double blind) and ≤2 years (extension). The following measurements were made: 24-week (primary outcome; double blind) and 12-week peptic ulcer recurrence rate, 24-week GI bleeding rate, cumulative incidences of peptic ulcer recurrence and GI bleeding, treatment-emergent adverse events, laboratory results, serum gastrin and pepsinogen I/II concentrations.. The 24-week peptic ulcer recurrence rate was 2.8%, 0.5% and 1.5% in the lansoprazole 15 mg, vonoprazan 10 mg and vonoprazan 20 mg groups, respectively. Vonoprazan was non-inferior (Farrington and Manning test: margin 8.7%, significance level 2.5%) to lansoprazole. In the post hoc analyses of the extension study, peptic ulcer recurrence rates were significantly lower with vonoprazan 10 mg (log-rank test, P=0.039), but not vonoprazan 20 mg (P=0.260), compared with lansoprazole 15 mg. GI bleeding rates were higher with lansoprazole compared with two doses of vonoprazan in both 24-week study and extension study.. Vonoprazan (10 and 20 mg) was as effective as lansoprazole (15 mg) in preventing peptic ulcer recurrence during LDA therapy, had a similar long-term safety profile and was well tolerated.. NCT01452763; NCT01456247.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Aspirin; Double-Blind Method; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Japan; Lansoprazole; Male; Middle Aged; Peptic Ulcer; Pyrroles; Recurrence; Secondary Prevention; Sulfonamides; Treatment Outcome

Vonoprazan, a potassium-competitive acid blocker, is expected to improve the healing of endoscopic submucosal dissection (ESD)-induced gastric ulcers compared with proton pump inhibitors (PPIs).. To compare the healing status of ESD-induced gastric ulcers and the incidence of post-ESD bleeding between subjects treated with vonoprazan for 5 weeks and those treated with PPIs for 8 weeks.. Patients in the vonoprazan group (n = 75) were prospectively enrolled, whereas patients in the PPI group (n = 150) were selected for a 2:1 matched historical control cohort according to baseline characteristics including gastric ulcer size immediately following ESD, age, sex and status of Helicobacter pylori infection. Two controls per case of vonoprazan-treated group were matched with a margin of 20% in terms of ulcer size and a margin of 5 years in terms of their age.. Although a higher number of completely healed ulcers was observed in the PPI group (95/150, 63.3%) than that in the vonoprazan group (14/75, 18.7%; P < 0.001), the ulcer size reduction rates, which were 96.0 ± 6.7% in the vonoprazan group and 94.7 ± 11.6% in the PPI group, were not significantly different (P = 0.373). The post-ESD bleeding incidence in the vonoprazan group (1/75, 1.3%) was less than that in the PPI group (15/150, 10.0%; P = 0.01). The factors affecting post-ESD bleeding incidence were the type of acid secretion inhibitor (P = 0.016) and use of an anti-thrombotic agent (P = 0.014).. Vonoprazan significantly reduced post-endoscopic submucosal dissection bleeding compared with PPIs.

Topics: Adenoma; Aged; Aged, 80 and over; Endoscopic Mucosal Resection; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Postoperative Complications; Proton Pump Inhibitors; Pyrroles; Rabeprazole; Stomach Neoplasms; Stomach Ulcer; Sulfonamides; Wound Healing

Low-dose aspirin (LDA) is used to prevent recurrent cardiovascular (CV) events, but is associated with upper gastrointestinal (GI) bleeding; concomitant use of a proton pump inhibitor (PPI) reduces this risk. This study aimed to assess the cost-effectiveness of vonoprazan compared with PPIs (lansoprazole and esomeprazole) in patients taking LDA for secondary prevention of CV events.Methods and Results: A Markov simulation model was developed to predict the number of GI bleeding and acute CV events using 3 strategies (vonoprazan+LDA, esomeprazole+LDA, and lansoprazole+LDA), which were translated into quality-adjusted life-years (QALYs) and costs. Transition probabilities and utilities were derived from the results of published literature, and medical costs were based on the Japanese National Health Insurance fee table and claims databases in 2020. Outcomes were projected over 30 years starting at age 65 years and discounted at 2% annually. Expected costs with esomeprazole 20 mg, lansoprazole 15 mg and vonoprazan 10 mg were JPY 1,225,657, JPY 943,930, and JPY 1,059,510, respectively. The QALY gain for vonoprazan vs. esomeprazole was 0.35, thus vonoprazan was dominant against esomeprazole. The QALY gain for vonoprazan vs. lansoprazole was 0.29 and the incremental cost-effectiveness ratio (ICER) was JPY 398,551, thus, vonoprazan was more cost-effective than lansoprazole.. Vonoprazan is dominant or cost-effective compared with esomeprazole and lansoprazole in patients taking LDA for secondary prevention of CV events.

Topics: Aged; Aspirin; Cardiovascular Diseases; Cost-Benefit Analysis; Esomeprazole; Gastrointestinal Hemorrhage; Humans; Japan; Lansoprazole; Proton Pump Inhibitors; Pyrroles; Secondary Prevention

Vonoprazan has been launched as an alternative to proton-pump inhibitors (PPIs). This was the first study to compare the occurrence of upper gastrointestinal bleeding (UGIB) with vonoprazan treatment to that with PPI treatment in patients with ischemic heart disease (IHD) taking ≥2 antithrombotic agents, including those receiving dual antiplatelet therapy (DAPT).. Using Japanese Diagnosis Procedure Combination data from 2016 to 2017, we identified 16,415 patients with IHD who were prescribed ≥2 antithrombotic agents, including new antiplatelet medication with concurrent vonoprazan (n = 2226 or PPIs n = 14,189). UGIB occurrence was analyzed using an inverse probability-weighted Cox proportional hazards model. Non-inferiority of vonoprazan to PPI treatment for UGIB occurrence was assessed.. Six-month incidence of UGIB in patients treated with vonoprazan and PPIs was 3.14% 70/2226 and 4.17% (591/14,189), respectively. The adjusted hazard ratio (aHR) of 0.84 was significantly below the non-inferiority margin (HR 2.06) (p < 0.0001), and thus demonstrated that vonoprazan treatment was non-inferior to PPIs in terms of occurrence of UGIB events. The difference between the 2 treatments was also not statistically significant [aHR 0.84; 95% confidence interval (CI): 0.65-1.07; p = 0.154). In a subgroup analysis, UGIB occurrence with vonoprazan and other PPI treatment in patients receiving DAPT was 2.82% (22/779) and 3.96% (209/5276) respectively; a non-significant difference (aHR 0.74; 95% CI: 0.48-1.16; p = 0.189) that demonstrated non-inferiority (p < 0.0001).. Vonoprazan was non-inferior to PPIs in terms of UGIB occurrence over 6 months in patients with IHD receiving ≥2 antithrombotic agents, including new antiplatelet medication.

Topics: Aged; Asian People; Databases, Factual; Female; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Humans; Japan; Male; Myocardial Ischemia; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Pyrroles; Retrospective Studies; Sulfonamides

Vonoprazan is a potassium-competitive acid blocker (P-CAB). It is often used in Japan for Helicobacter pylori (H pylori) eradication, gastroesophageal reflux disease, and endoscopic submucosal dissection (ESD) ulcers and bleeding. This meta-analysis aims to evaluate whether vonoprazan has better therapeutic effect on ESD-induced ulcers and bleeding than proton pump inhibitors (PPIs) at different length of treatment periods (2, 4, and 8 weeks).. This meta-analysis will include both randomized controlled trials (RCTs) and observational studies discussing the effectiveness of vonoprazan and PPIs on ESD-induced ulcers and bleeding. Information of studies will be collected from PubMed, Cochrane Library, ClinicalTrials.gov, and Google Scholar. Studies will be selected according to the eligibility criteria and data will be extracted by 2 people and compared with each other to keep in consistency. Cochrane risk of bias tool will be used to assess RCTs and the Newcastle-Ottawa Quality Assessment Scale will be used to assess the observational studies. Meta-analysis based on the random-effects model will be conducted to compare the differences of ulcers' shrinkage ratios (%) and the odds ratios (OR) of scars' stages and delayed bleeding. Publication bias will be evaluated using funnel plots and Egger's regression test. Heterogeneity will be assessed with the I statistics. Sensitivity analysis will be conducted on follow-up periods. The evidential quality of the findings will be assessed with the Grading of Recommendations Assessment Development and Evaluation (GRADE) profiler.. The findings of the present systematic review will be critical for physicians, patients, and policymakers regarding the use of vonoprazan in ESD-induced ulcers.. PROSPERO registration number: CRD42018116855.

Topics: Endoscopic Mucosal Resection; Epidemiologic Studies; Gastrointestinal Hemorrhage; Humans; Meta-Analysis as Topic; Postoperative Complications; Proton Pump Inhibitors; Pyrroles; Randomized Controlled Trials as Topic; Research Design; Stomach Neoplasms; Stomach Ulcer; Sulfonamides; Systematic Review as Topic; Time Factors

Topics: Anti-Bacterial Agents; Drug Therapy, Combination; Gastric Acid; Gastric Mucosa; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Helicobacter Infections; Helicobacter pylori; Hemostasis, Endoscopic; Humans; Hydrogen-Ion Concentration; Proton Pump Inhibitors; Pyrroles; Sulfonamides; Treatment Outcome

Helicobacter pylori (H. pylori) eradication rarely develops into antibiotic-associated hemorrhagic colitis (AAHC), in which the etiology of colitis remains unclear. We herein report a rare case of AAHC caused by second-line therapy for H. pylori eradication.. A 65-year-old female was administered second-line therapy for H. pylori composed of 1500 mg of amoxicillin, 500 mg of metronidazole and 40 mg of vonoprazan for 7 days because of first-line therapy failure. A day after completing second-line therapy, she complained of abdominal pain and hematochezia. Colonoscopy revealed a hemorrhage and edematous mucosa with no transparent vascular pattern in the transverse colon. A bacterial culture detected Klebsiella oxytoca (K. oxytoca), but no other pathogenic bacteria. A drug-induced lymphocyte stimulation test (DLST) showed positive reactions for both amoxicillin and metronidazole. According to these findings, the patient was diagnosed with AAHC. Bowel rest for 6 days relieved her abdominal pain and hematochezia.. The present case developed AAHC caused by second-line therapy for H. pylori eradication. The pathogenesis is considered to be associated with microbial substitution as well as a delayed-type allergy to antibiotics, suggesting that AAHC is a potential adverse event of second-line therapy for H. pylori eradication.

Topics: Abdominal Pain; Aged; Amoxicillin; Biopsy; Colitis; Colon; Colonoscopy; Female; Gastrointestinal Hemorrhage; Helicobacter Infections; Helicobacter pylori; Hemorrhage; Humans; Klebsiella oxytoca; Metronidazole; Mucous Membrane; Pyrroles; Rare Diseases; Sulfonamides