Decline incidence in upper gastrointestinal bleeding in several recent years: data of the Japan claims database of 13 million accumulated patients.

This study was to examine the recent trends in upper gastrointestinal bleeding in Japan using a large-scale real-world database. The incidence of upper gastrointestinal bleeding was evaluated in the Japan Medical Data Center claims database of 13,019,713 patients aged 20 to 74 years with traceability for 3 months from 2009 to 2014. The incidence was compared with peptic ulcers and gastroesophageal reflux disease. The prescription of medications was also evaluated. The incidence of bleeding was 0.137%, 0.121%, 0.113%, 0.106%, 0.099%, and 0.105% during 2009 to 2014 with a time-dependent decline (p<0.001). Peptic ulcers (>10 times higher than the incidence of bleeding) decreased with time (p<0.001), whereas gastroesophageal reflux disease increased (p = 0.006). Upper gastrointestinal bleeding was higher in male patients and older patients (60-74 years old) (p<0.001 respectively). The prescription rate of antithrombotic medications and proton pump inhibitors increased from 2009 to 2014 (p<0.001 respectively). The incidence of upper gastrointestinal bleeding decreased from 2009 to 2014 in this relatively large-scale real-world database in Japan, concomitant with the decrease in peptic ulcers. The decreased incidence might have been due to changes in the disease structure and therapeutic strategies over time.

Correction to: A case-control study of the risk of upper gastrointestinal mucosal injuries in patients prescribed concurrent NSAIDs and antithrombotic drugs based on data from the Japanese national claims database of 13 million accumulated patients.

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A case-control study of the risk of upper gastrointestinal mucosal injuries in patients prescribed concurrent NSAIDs and antithrombotic drugs based on data from the Japanese national claims database of 13 million accumulated patients.

BACKGROUND: We aimed to identify the adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and antithrombotics on the upper gastrointestinal (GI) mucosa in a clinical setting as a case-control study using a large-scale medical database in Japan. METHODS: We evaluated the risk of upper GI mucosal injuries in patients receiving NSAIDs and antithrombotics using the Japan Medical Data Center claims database with data for 13 million accumulated patients, from January 2009 to December 2014. Endoscopically evaluated upper GI mucosal injuries were peptic ulcers (n = 143,271), upper GI bleeding (n = 10,545), and gastroesophageal reflux disease (n = 154,755). For each patient, ten controls were matched by age, sex, and diagnosis month. RESULTS: The odds ratio (OR) for peptic ulcers was 1.45, 1.31, 1.50, 1.53, and 1.62; for upper GI bleeding: 1.76, 1.62, 1.96, 1.82, and 2.38; and for gastroesophageal reflux disease: 1.54, 1.41, 1.89, 1.67, and 1.91 for NSAIDs, COX-2 selective inhibitors, low-dose aspirin, antiplatelet drugs, and anticoagulants, respectively (all statistically significant: P < 0.001). Polypharmacy with NSAIDs and antithrombotic drugs increased the risk of upper GI injuries compared with single-drug therapy. The injury risk was also increased by lifestyle-related diseases, including diabetes mellitus and hyperlipidemia. CONCLUSIONS: This case-control study using the large organized Japanese claims database provided the risk of upper GI mucosal injuries in patients receiving NSAIDs and antithrombotic drugs.

Long-term efficacy and safety of rabeprazole in patients taking low-dose aspirin with a history of peptic ulcers: a phase 2/3, randomized, parallel-group, multicenter, extension clinical trial.

A 24-week, double-blind, clinical trial of rabeprazole for the prevention of recurrent peptic ulcers caused by low-dose aspirin (LDA) has been reported, but trials for longer than 24 weeks have not been reported. The aim of this study is to assess the long-term efficacy and safety of rabeprazole for preventing peptic ulcer recurrence on LDA therapy. Eligible patients had a history of peptic ulcers on long-term LDA (81 or 100 mg/day) therapy. Patients with no recurrence of peptic ulcers at the end of the 24-week double-blind phase with rabeprazole (10- or 5-mg once daily) or teprenone (50 mg three times daily) entered the extension phase. Rabeprazole doses were maintained for a maximum of 76 weeks, including the double-blind 24-week period and the extension phase period (long-term rabeprazole 10- and 5-mg groups). Teprenone was randomly switched to rabeprazole 10 or 5 mg for a maximum of 52 weeks in the extension phase (newly-initiated rabeprazole 10- and 5-mg groups). The full analysis set consisted of 151 and 150 subjects in the long-term rabeprazole 10- and 5-mg groups, respectively, and the cumulative recurrence rates of peptic ulcers were 2.2 and 3.7%, respectively. Recurrent peptic ulcers were not observed in the newly-initiated rabeprazole 10- and 5-mg groups. No bleeding ulcers were reported. No clinically significant safety findings, including cardiovascular events, emerged. The use of long-term rabeprazole 10- and 5-mg once daily prevents the recurrence of peptic ulcers in subjects on low-dose aspirin therapy, and both were well-tolerated.

Dose-response relationships of rabeprazole 5, 10, 20, and 40 mg once daily on suppression of gastric acid secretion through the night in healthy Japanese individuals with different CYP2C19 genotypes.

PURPOSE: This study was designed to investigate the antisecretory activity of rabeprazole administered once daily in doses of 5, 10, 20, and 40 mg and different cytochrome P450 2C19 (CYP2C19) genotypes on gastric pH in healthy individuals. Additional objectives were delineating the nighttime from the daytime effect and determining the relationships between the pharmacokinetics and pharmacodynamics of rabeprazole. METHODS: Eight individuals of each of the three genotypes of CYP2C19-homozygous extensive metabolizers (homo-EMs), heterozygous EMs (hetero-EMs), and poor metabolizers (PMs)-were recruited. Twenty-four individuals received a once-daily dose, with dosing interval 24 h of 5, 10, 20, or 40 mg rabeprazole for 5 days in a 4-period crossover fashion. Twenty-four-hour intragastric pH and plasma rabeprazole concentrations were determined on day 5. RESULTS: A dose-dependent increase in median pH and in pH 4 holding time was observed across all CYP2C19 genotypes. When rabeprazole was increased from 20 mg to 40 mg, the differences and 95% confidence intervals (CIs) of nighttime pH 4 holding time between 40 mg and 20 mg in homo-EMs, hetero-EMs, and PMs were 8.0% (-5.0% -21.0%), 28.7% (15.7% -41.6%), and 16.9% (3.9% -29.9%), respectively. The relationship between the area under the plasma concentration-time curve up to the last time point at which rabeprazole was quantifiable (AUC(0-t)) and the pH 4 holding time could be described using a sigmoid maximum effect (E(max)) model. CONCLUSIONS: Our data demonstrate that increasing rabeprazole dose up to 40 mg once daily results in an increasing pharmacodynamic effect, which is most apparent for the control of nocturnal gastric acid secretion.