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1.
J Cardiol ; 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32184027

RESUMO

BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

2.
J Gastroenterol ; 54(12): 1083-1095, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31396703

RESUMO

BACKGROUND: Gastroesophageal reflux disease (GERD) can be treated using a vonoprazan-first strategy (first-line treatment with vonoprazan), or esomeprazole-first/rabeprazole-first strategies (first-line treatment with proton-pump inhibitors [PPIs], esomeprazole/rabeprazole, followed by a switch to vonoprazan). This cost-utility analysis used long-term simulation modeling to evaluate the cost-effectiveness of a vonoprazan-first strategy compared with the esomeprazole-first and rabeprazole-first strategies. METHODS: A Markov simulation model was developed to evaluate the cost-effectiveness of vonoprazan-first, esomeprazole-first, and rabeprazole-first strategies, comprising healing and maintenance therapies, over 5 years (4-week cycles). Healing therapy began with the administration of a normal dose of drug per real-world practice. If patients were not healed endoscopically, either a longer duration of healing therapy was provided (vonoprazan), the dose was increased (rabeprazole), or patients were switched to vonoprazan (immediately for esomeprazole, and after dose-escalation for rabeprazole, respectively). Healed patients received maintenance (lower/same dose as healing therapy). Recurrence resulted in re-challenge with healing therapy. Transition probabilities were derived from the results of indirect comparisons (network meta-analysis) and costs calculated from the Japanese payer perspective. Outcomes were defined as quality-adjusted life years (QALYs), with utilities based on published values. RESULTS: Expected costs of the vonoprazan-, esomeprazole-, and rabeprazole-first strategies were ¥36,194, ¥76,719, and ¥41,105, respectively, over 5 years. QALY gains for vonoprazan-first strategy versus the esomeprazole- and rabeprazole-first strategies were 0.014 and 0.003, respectively. Both estimated incremental cost-effectiveness ratios were dominant and robust to two sensitivity analyses. CONCLUSIONS: Vonoprazan-first strategy increased QALYs and appeared to be cost-effective for GERD patients compared with the esomeprazole- or rabeprazole-first strategies.

3.
J Gastroenterol Hepatol ; 34(12): 2112-2117, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31264254

RESUMO

BACKGROUND AND AIM: Both clarithromycin-resistant Helicobacter pylori and CYP2C19 polymorphisms may be passed down for generations and are known risk factors for the failure of H. pylori eradication therapy. However, no study has evaluated the risk of clarithromycin triple therapy failure in patients with a parental history of such failure. This study investigated the association between a history of clarithromycin triple therapy failure in parents and clarithromycin triple therapy failure in the offspring. METHODS: This cross-sectional study was conducted using a large administrative claims database of 3 100 000 insured individuals. We identified 404 patients who had both personal and parental records of prescriptions for first-line clarithromycin triple therapy between January 2005 and February 2018. Failure of clarithromycin triple therapy was defined as treatment with second-line therapy after having received first-line clarithromycin triple therapy. A parental history of clarithromycin triple therapy failure was defined as failure of clarithromycin triple therapy by either the father or the mother. Odds ratios were estimated using logistic regression models adjusted for age, sex, diabetes mellitus, and peptic ulcer. RESULTS: The incidence of clarithromycin triple therapy failure was 22.5% (91/404). Based on univariate analysis (odds ratio [95% confidence interval], 1.90 [1.10-3.29]) and multivariable analysis (odds ratio [95% confidence interval], 1.93 [1.10-3.39]), parental history of clarithromycin triple therapy failure was associated with failure of clarithromycin triple therapy in the offspring. CONCLUSION: A parental history of clarithromycin triple therapy failure is a risk factor for failure of clarithromycin triple therapy in the offspring.

4.
Digestion ; : 1-9, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31216549

RESUMO

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.

5.
J Gastroenterol Hepatol ; 34(8): 1316-1328, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30883868

RESUMO

BACKGROUND AND AIM: Gastroesophageal reflux disease (GERD) is a common disease caused by reflux of gastric contents to the esophagus. Proton-pump inhibitors (PPIs) are recommended as a first-line therapy to treat GERD. Recently, a new potassium-competitive acid blocker, vonoprazan, was launched in Japan. We aimed to evaluate the comparative efficacy of vonoprazan and other PPIs in healing GERD. METHODS: We used MEDLINE and the Cochrane Central Register of Controlled Trials to search the literature. Double-blind randomized controlled trials for PPIs and/or vonoprazan that were published in English or Japanese and assessed healing effects in adult GERD patients were included. To estimate the comparative efficacy of treatments, we performed a Bayesian network meta-analysis to assess the consistency assumption. RESULTS: Of 4001 articles identified in the database, 42 studies were eligible. One study was hand-searched and added to the analysis. For the main analysis of healing effects at 8 weeks, odds ratios (ORs) of vonoprazan (20 mg daily) to esomeprazole (20 mg), rabeprazole (20 mg), lansoprazole (30 mg), and omeprazole (20 mg) were 2.29 (95% credible interval, 0.79-7.06), 3.94 (1.15-14.03), 2.40 (0.90-6.77), and 2.71 (0.98-7.90), respectively. Subgroup analysis for patients with severe esophagitis at baseline showed significantly higher ORs for vonoprazan versus most of the comparator PPIs. CONCLUSIONS: This analysis shows that the GERD healing effect of vonoprazan is higher than that of rabeprazole (20 mg) but not higher than other PPIs. Subgroup analysis indicated that vonoprazan is more effective than most PPIs for patients with severe erosive esophagitis.


Assuntos
Esofagite Péptica/tratamento farmacológico , Refluxo Gastroesofágico/tratamento farmacológico , Inibidores da Bomba de Prótons/uso terapêutico , Pirróis/uso terapêutico , Sulfonamidas/uso terapêutico , Cicatrização/efeitos dos fármacos , Teorema de Bayes , Esofagite Péptica/diagnóstico , Esofagite Péptica/fisiopatologia , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/fisiopatologia , Humanos , Metanálise em Rede , Seleção de Pacientes , Inibidores da Bomba de Prótons/efeitos adversos , Pirróis/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Índice de Gravidade de Doença , Sulfonamidas/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
6.
J Gastroenterol ; 54(8): 718-729, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30919071

RESUMO

BACKGROUND: Long-term maintenance treatment of gastroesophageal reflux disease (GERD) is important to prevent relapse. Proton-pump inhibitors (PPIs) are used for both treatment and maintenance therapy of GERD. Recently, a potassium-competitive acid blocker vonoprazan was launched in Japan. We evaluated the comparative efficacy of vonoprazan and other PPIs for GERD maintenance. METHODS: A systematic literature search was performed using MEDLINE and Cochrane Central Register of Controlled Trials. Double-blind randomized controlled trials (RCTs) of PPIs, vonoprazan, and placebo for GERD maintenance published in English or Japanese were selected. Among them, studies conducted at the recommended dose and for the recommended use, and containing information on maintenance rate based on endoscopic assessment, were included. The comparative efficacies of treatments were estimated by performing a Bayesian network meta-analysis, which assessed the consistency assumption. Outcomes were number or rate of patients who maintained remission. RESULTS: Of 4001 articles identified, 22 RCTs were eligible for analysis. One study published as an abstract was hand-searched and added. The consistency hypothesis was not rejected for the analysis. The odds ratio of vonoprazan 10 mg to each PPI was 13.92 (95% credible interval [CI] 1.70-114.21) to esomeprazole 10 mg; 5.75 (95% CI 0.59-51.57) to rabeprazole 10 mg; 3.74 (95% CI 0.70-19.99) to lansoprazole 15 mg; and 9.23 (95% CI 1.17-68.72) to omeprazole 10 mg. CONCLUSIONS: The efficacy of vonoprazan in GERD maintenance treatment may be higher than that of some PPIs. However, a direct comparison of vonoprazan and PPIs is required to confirm these effects.

7.
Free Radic Biol Med ; 51(9): 1799-805, 2011 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-21906674

RESUMO

Nonsteroidal anti-inflammatory drugs are the drugs of choice in the treatment of rheumatoid arthritis (RA) because of their rapid analgesic effect. However, they induce severe gastric damage in RA patients and animals by a process mediated by reactive oxygen species (ROS). Nitroxides (nitroxyl radicals) are widely used as imaging agents and antioxidants to explore the role of ROS generation in the pathogenesis of disease. In this study, the effectiveness of the newly synthesized nitroxides 8-aza-7,7,9,9-tetramethyl-1,4-dioxaspiro[4.5]undecan-8-oxyl (compound 1) and 4-oxo-2,2,6,6-tetraethylpiperidine-1-oxyl (compound 2) in the prevention of gastric ulcers in adjuvant arthritis rats treated with indomethacin was evaluated by monitoring the reaction of reactive oxygen species in gastric tissue with Overhauser-enhanced magnetic resonance imaging (OMRI). Pretreatment with all tested nitroxides suppressed the ulcers induced by indomethacin treatment in arthritic rats. OMRI using compounds 1 and 2 as well as 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) demonstrated a redox imbalance in the stomach of these rats. Lipid peroxide and interleukin (IL)-1ß levels in the gastric mucosa were significantly suppressed by compound 1 and TEMPOL, whereas CINC/gro, a member of the IL-8 family, was significantly suppressed by compound 1 only. These results suggest that the preventive effects of nitroxides on gastric ulcers may operate by different mechanisms.


Assuntos
Artrite Experimental/metabolismo , Óxidos de Nitrogênio/metabolismo , Úlcera Gástrica/prevenção & controle , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Antioxidantes/metabolismo , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Indometacina/efeitos adversos , Imagem por Ressonância Magnética , Masculino , Ratos , Ratos Endogâmicos , Espécies Reativas de Oxigênio/metabolismo , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo
8.
Free Radic Biol Med ; 49(11): 1703-9, 2010 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-20828609

RESUMO

Nitroxyl radicals (nitroxide) have great potential advantages as spin probes, antioxidants, contrast agents, and radiation-protecting agents. However, they are readily reduced by reductants in cells and lose their paramagnetic nature. Recently, tetraethyl-substituted nitroxyl radicals have been reported to have high stability toward reduction by ascorbic acid (AsA). We report the general considerations of tetraethyl nitroxyl radicals for in vivo application. The reason for the low reactivity to AsA reduction was the positive value of Gibbs energy between the tetraethyl nitroxyl radical and AsA. Further, these compounds had an inhibitory effect on lipid peroxidation despite having AsA resistance. They had low antiproliferative effects in HepG2 cells and HUVECs and did not have a lowering effect on blood pressure in animals. Further, after intravenous injection, the ESR signal intensities of tetraethyl-substituted piperidine nitroxyl radicals were very stable in mice over 20 min. These results suggest that tetraethyl-substituted nitroxyl radicals have stability against bioreduction with reductants such as AsA and confer onto them features as antioxidants and paramagnetic tracers/contrast agents. Hence, they will be useful in identifying the foci of oxidative stress in vivo using redox-based imaging approaches.


Assuntos
Óxidos de Nitrogênio/metabolismo , Óxidos de Nitrogênio/farmacologia , Animais , Antioxidantes/efeitos adversos , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Ácido Ascórbico , Pressão Sanguínea/efeitos dos fármacos , Células Cultivadas , Meios de Contraste/efeitos adversos , Meios de Contraste/metabolismo , Meios de Contraste/farmacologia , Estabilidade de Medicamentos , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Células Hep G2 , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Óxidos de Nitrogênio/efeitos adversos , Oxirredução , Ratos , Ratos Endogâmicos SHR , Ratos Sprague-Dawley
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