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Chen PH, Tsai CL, Hsieh YW, Cho DY, Tsai FJ, Lin CL, Liao HY. Antihyperlipidemic drugs mitigate the elevated incidence of peptic ulcer disease caused by hyperlipidemia: A cohort study. J Chin Med Assoc 2024; 87:961-968. [PMID: 39118217 DOI: 10.1097/jcma.0000000000001145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/10/2024] Open
Abstract
BACKGROUND Several risk factors for peptic ulcer disease (PUD) have been identified; however, the recurrence rate of PUD remains high even with standard ulcer treatments. High cholesterol levels have been proposed as a risk factor for PUD, but clinical evidence remains limited. Therefore, this database study investigated whether hyperlipidemia increases PUD risk and whether antihyperlipidemic drugs reduce this risk. METHODS A long-term cohort design was adopted, and Taiwan's National Health Insurance Research Database was used to enroll patients diagnosed with hyperlipidemia between 2000 and 2016. Patients without hyperlipidemia were randomly matched based on variables such as age and gender to establish a comparison cohort at a 1:1 ratio. Another cohort study was conducted to determine whether antihyperlipidemic drugs or red yeast rice prescriptions can reduce the incidence of PUD in patients with hyperlipidemia. RESULTS The overall incidence of PUD was 1.48 times higher in the hyperlipidemia cohort (203,235 patients) than in the nonhyperlipidemia cohort (adjusted hazard ratio, 1.48; 95% CI, 1.46-1.50; p < 0.001). Among the patients with hyperlipidemia, those who used antihyperlipidemic drugs with or without red yeast rice prescriptions exhibited a lower risk of developing PUD relative to those who did not use them; the adjusted hazard ratios were 0.33 (95% CI, 0.21-0.52) and 0.81 (95% CI, 0.78-0.84), respectively. When the cumulative exposure to antihyperlipidemic drugs and red yeast rice prescriptions increased, the risk of developing PUD showed a decreasing trend, which was statistically significant for antihyperlipidemic drugs but not for red yeast rice. CONCLUSION Hyperlipidemia is associated with a higher risk of PUD, which can be reduced through the administration of antihyperlipidemic drugs with or without red yeast rice prescriptions.
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Affiliation(s)
- Pei-Hsien Chen
- Department of Chinese Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan, ROC
| | - Chiu-Lin Tsai
- Department of Chinese Medicine Pharmacy, China Medical University Hospital, China Medical University, Taichung, Taiwan, ROC
| | - Yow-Wen Hsieh
- Department of Pharmacy, China Medical University Hospital, China Medical University, Taichung, Taiwan, ROC
- Graduate Institute of Pharmacy, China Medical University, Taichung, Taiwan, ROC
| | - Der-Yang Cho
- Translational Cell Therapy Center, Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan, ROC
- Department of Neurosurgery, China Medical University Hospital, China Medical University, Taichung, Taiwan, ROC
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, ROC
| | - Fuu-Jen Tsai
- School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan, ROC
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan, ROC
- Division of Medical Genetics, China Medical University Children's Hospital, China Medical University, Taichung, Taiwan, ROC
- Department of Medical Laboratory Science & Biotechnology, Asia University, Taichung, Taiwan, ROC
| | - Cheng-Li Lin
- Management Office for Health Data, China Medical University Hospital, Taichung, China Medical University, Taiwan, ROC
| | - Hsien-Yin Liao
- School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan, ROC
- Department of Acupuncture, China Medical University Hospital, China Medical University, Taichung, Taiwan, ROC
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Kagawa T, Ishikawa S, Hidaka Y, Colvin HS, Nakanishi A, Ohkawa J, Negishi S, Yasutomi E, Yamauchi K, Okamoto K, Sakakihara I, Izumikawa K, Yamamoto K, Takahashi S, Tanaka S, Matsuura M, Wato M, Hasui T, Inaba T. Risk factors for postgastric endoscopic submucosal dissection bleeding in direct oral anticoagulant users. Dig Endosc 2024; 36:1130-1139. [PMID: 38695106 DOI: 10.1111/den.14806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 03/27/2024] [Indexed: 10/12/2024]
Abstract
OBJECTIVES Bleeding after endoscopic submucosal dissection (ESD) for gastric tumors in patients taking antithrombotic drugs, in particular direct oral anticoagulants (DOACs), remains unresolved; therefore, we evaluated the risk factors for post-ESD bleeding and drug differences in patients taking DOACs. METHODS We included 278 patients taking antithrombotic drugs who underwent gastric ESD between January 2017 and March 2022. Antithrombotic drugs were withdrawn following the 2017 guidelines (Appendix on anticoagulants including DOACs). To further clarify differences in antithrombotic agents' effects, the peri-cancerous mucosa in the resected specimen was pathologically evaluated according to the Updated Sydney System. Multivariate analysis was performed to assess the risk of post-ESD bleeding. RESULTS The incidence of post-ESD bleeding in patients taking DOACs was 19.6% (10/51). Among patients taking antithrombotic drugs, DOACs were identified as a possible factor involved in post-ESD bleeding (odds ratio [OR] 4.92). Among patients taking DOACs, possible factors included resection length diameter ≥30 mm (OR 3.72), presence of neutrophil infiltration (OR 2.71), lesions occurring in the lower third of stomach (OR 2.34), and preoperative antiplatelet use (OR 2.22). Post-ESD bleeding by DOAC type was 25.0% of patients (4/16) receiving apixaban, in 20.0% (3/15) receiving edoxaban, in 21.4% (3/14) receiving rivaroxaban, and in none of those receiving dabigatran. CONCLUSIONS The administration of DOACs was shown to be a possible factor involved in post-ESD bleeding, and risk factors for patients taking DOACs included neutrophil infiltration. The pharmacological differences in the effects of DOACs contributing to bleeding in gastric ulcers suggest comparatively less bleeding with dabigatran after ESD.
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Affiliation(s)
- Tomo Kagawa
- Department of Gastroenterology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Shigenao Ishikawa
- Department of Gastroenterology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Yu Hidaka
- Department of Medical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hugh Shunsuke Colvin
- Department of Gastroenterology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Akira Nakanishi
- Department of Gastroenterology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Jumpei Ohkawa
- Department of Gastroenterology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Shin Negishi
- Department of Gastroenterology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Eriko Yasutomi
- Department of Gastroenterology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Kenji Yamauchi
- Department of Gastroenterology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Kunio Okamoto
- Department of Gastroenterology, Kagawa Prefectural Central Hospital, Kagawa, Japan
- Department of Medical Oncology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Ichiro Sakakihara
- Department of Gastroenterology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Koichi Izumikawa
- Department of Gastroenterology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Kumiko Yamamoto
- Department of Gastroenterology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Sakuma Takahashi
- Department of Gastroenterology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Shigetomi Tanaka
- Department of Gastroenterology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Mihoko Matsuura
- Department of Gastroenterology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Masaki Wato
- Department of Gastroenterology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Toshimi Hasui
- Department of Gastroenterology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Tomoki Inaba
- Department of Gastroenterology, Kagawa Prefectural Central Hospital, Kagawa, Japan
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Bai CY, Tian W, Zhang Q. Clinical study on microscopic syndrome differentiation and traditional Chinese medicine treatment for liver stomach disharmony in chronic gastritis. World J Gastrointest Surg 2024; 16:1377-1384. [PMID: 38817300 PMCID: PMC11135293 DOI: 10.4240/wjgs.v16.i5.1377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 04/05/2024] [Accepted: 04/11/2024] [Indexed: 05/23/2024] Open
Abstract
BACKGROUND Chronic gastritis (CG) is a common gastrointestinal disorder characterized by inflammation of the stomach lining. Liver-stomach disharmony (LSD) syndrome is believed to contribute to CG symptoms. AIM To evaluate the efficacy and safety of microcosmic syndrome differentiation and Chinese herbal medicine (CHM) treatment in patients with CG and LSD syndrome. METHODS Sixty-four patients with CG and LSD syndrome were randomly divided into two groups: The treatment group received CHM based on microcosmic syndrome differentiation and the control group received conventional Western medicine. The treatment course lasted 12 wk. The primary outcome was improvement in dyspeptic symptoms, measured using the Nepean Dyspepsia Index. The secondary outcomes included the improvement rate of endoscopic findings, histopathological findings, and microcosmic syndrome scores and the incidence of adverse events. RESULTS After 12 wk of treatment, the treatment group showed significantly greater improvement in dyspeptic symptoms than the control group (93.75% vs 65.63%, P < 0.01). The treatment group also showed a significantly higher improvement rate in endoscopic findings than the control group (81.25% vs 53.13%, P < 0.05). The improvement rates of histopathological findings and microcosmic syndrome scores were not significantly different between the two groups (P > 0.05). No serious adverse events were observed in either group. CONCLUSION Microcosmic syndrome differentiation and CHM treatment can effectively improve dyspeptic symptoms and endoscopic findings in patients with CG and LSD syndrome and have a good safety profile. Further studies with larger sample sizes and longer follow-up periods are required to confirm the long-term efficacy and mechanism of action of this treatment.
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Affiliation(s)
- Chun-Yan Bai
- Department of Rehabilitation Medicine, Beijing Aerospace General Hospital, Beijing 100076, China
| | - Wei Tian
- Department of Rehabilitation Medicine, People’s Hospital of Hengshui, Hengshui 053000, Hebei Province, China
| | - Qian Zhang
- Department of Internal Medicine, Hebei Academy of Chinese Medicine Sciences, Shijiazhuang 050000, Hebei Province, China
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Mollace R, Gliozzi M, Macrì R, Tavernese A, Musolino V, Carresi C, Maiuolo J, Muscoli C, Tomino C, Rosano GM, Fini M, Volterrani M, Silvestrini B, Mollace V. Efficacy and Safety of Novel Aspirin Formulations: A Randomized, Double-Blind, Placebo-Controlled Study. Pharmaceutics 2022; 14:pharmaceutics14010187. [PMID: 35057084 PMCID: PMC8779026 DOI: 10.3390/pharmaceutics14010187] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 01/08/2022] [Accepted: 01/10/2022] [Indexed: 01/17/2023] Open
Abstract
Low-dose aspirin represents the best option in the secondary prevention of coronary artery disease, but its extensive use in primary prevention is limited by the occurrence of gastric mucosal lesions and increased risk of bleeding. We investigated the safety profile of a novel sublingual aspirin formulation in 200 healthy volunteers, randomly assigned to ten (n = 20 each) different 7-day once-daily treatment regimens. Gastric mucosal injury based on the modified Lanza score (MLS), the histopathology of gastric mucosa and the serum determination of thromboxane B2 (TXB2) and urinary 11-dehydro-TXB2 levels were evaluated at basal as well as after 7 days of each placebo or aspirin treatment regimen. In Groups A and B (placebo—oral and sublingual, respectively), no changes in MLS and in gastric mucosal micro-vessel diameter were found at day 7. In contrast, in Groups C and D (oral standard aspirin—100 and 50 mg daily, respectively), the median MLS was significantly increased. Very few changes were found in Groups E and F (standard sublingual aspirin—100 and 50 mg, respectively). Groups G and H (oral administration of micronized collagen-cogrinded aspirin) showed gastric protection compared to Groups C and D. Moreover, Groups I and L (sublingual collagen-cogrinded aspirin—100 and 50 mg, respectively) showed a significant reduction (Group I) or total abolition (Group L) of gastric mucosal lesions and no difference compared to the standard one in serum TXB2 and urinary 11-dehydro-TXB2 levels. In conclusion, our data show that the new formulation leads to a better safety profile compared to standard aspirin, representing a better therapeutic option for extended use in primary and secondary prevention of cardiovascular diseases.
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Affiliation(s)
- Rocco Mollace
- Department of Health Science, Institute of Research for Food Safety & Health IRC-FSH, University Magna Graecia, 88100 Catanzaro, Italy; (R.M.); (M.G.); (R.M.); (A.T.); (V.M.); (C.C.); (J.M.); (C.M.); (B.S.)
- IRCCS San Raffaele Pisana, Via di Valcannuta, 00163 Rome, Italy; (C.T.); (G.M.R.); (M.F.); (M.V.)
| | - Micaela Gliozzi
- Department of Health Science, Institute of Research for Food Safety & Health IRC-FSH, University Magna Graecia, 88100 Catanzaro, Italy; (R.M.); (M.G.); (R.M.); (A.T.); (V.M.); (C.C.); (J.M.); (C.M.); (B.S.)
| | - Roberta Macrì
- Department of Health Science, Institute of Research for Food Safety & Health IRC-FSH, University Magna Graecia, 88100 Catanzaro, Italy; (R.M.); (M.G.); (R.M.); (A.T.); (V.M.); (C.C.); (J.M.); (C.M.); (B.S.)
| | - Annamaria Tavernese
- Department of Health Science, Institute of Research for Food Safety & Health IRC-FSH, University Magna Graecia, 88100 Catanzaro, Italy; (R.M.); (M.G.); (R.M.); (A.T.); (V.M.); (C.C.); (J.M.); (C.M.); (B.S.)
| | - Vincenzo Musolino
- Department of Health Science, Institute of Research for Food Safety & Health IRC-FSH, University Magna Graecia, 88100 Catanzaro, Italy; (R.M.); (M.G.); (R.M.); (A.T.); (V.M.); (C.C.); (J.M.); (C.M.); (B.S.)
| | - Cristina Carresi
- Department of Health Science, Institute of Research for Food Safety & Health IRC-FSH, University Magna Graecia, 88100 Catanzaro, Italy; (R.M.); (M.G.); (R.M.); (A.T.); (V.M.); (C.C.); (J.M.); (C.M.); (B.S.)
| | - Jessica Maiuolo
- Department of Health Science, Institute of Research for Food Safety & Health IRC-FSH, University Magna Graecia, 88100 Catanzaro, Italy; (R.M.); (M.G.); (R.M.); (A.T.); (V.M.); (C.C.); (J.M.); (C.M.); (B.S.)
| | - Carolina Muscoli
- Department of Health Science, Institute of Research for Food Safety & Health IRC-FSH, University Magna Graecia, 88100 Catanzaro, Italy; (R.M.); (M.G.); (R.M.); (A.T.); (V.M.); (C.C.); (J.M.); (C.M.); (B.S.)
- IRCCS San Raffaele Pisana, Via di Valcannuta, 00163 Rome, Italy; (C.T.); (G.M.R.); (M.F.); (M.V.)
| | - Carlo Tomino
- IRCCS San Raffaele Pisana, Via di Valcannuta, 00163 Rome, Italy; (C.T.); (G.M.R.); (M.F.); (M.V.)
| | - Giuseppe Maria Rosano
- IRCCS San Raffaele Pisana, Via di Valcannuta, 00163 Rome, Italy; (C.T.); (G.M.R.); (M.F.); (M.V.)
| | - Massimo Fini
- IRCCS San Raffaele Pisana, Via di Valcannuta, 00163 Rome, Italy; (C.T.); (G.M.R.); (M.F.); (M.V.)
| | - Maurizio Volterrani
- IRCCS San Raffaele Pisana, Via di Valcannuta, 00163 Rome, Italy; (C.T.); (G.M.R.); (M.F.); (M.V.)
| | - Bruno Silvestrini
- Department of Health Science, Institute of Research for Food Safety & Health IRC-FSH, University Magna Graecia, 88100 Catanzaro, Italy; (R.M.); (M.G.); (R.M.); (A.T.); (V.M.); (C.C.); (J.M.); (C.M.); (B.S.)
| | - Vincenzo Mollace
- Department of Health Science, Institute of Research for Food Safety & Health IRC-FSH, University Magna Graecia, 88100 Catanzaro, Italy; (R.M.); (M.G.); (R.M.); (A.T.); (V.M.); (C.C.); (J.M.); (C.M.); (B.S.)
- IRCCS San Raffaele Pisana, Via di Valcannuta, 00163 Rome, Italy; (C.T.); (G.M.R.); (M.F.); (M.V.)
- Correspondence:
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Murata M, Sugimoto M. Effect of a rabeprazole half-dose twice daily on acid inhibition in patients with different CYP2C19 alleles. Eur J Clin Pharmacol 2020; 76:1253-1261. [PMID: 32488332 DOI: 10.1007/s00228-020-02917-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Accepted: 05/25/2020] [Indexed: 10/24/2022]
Abstract
PURPOSE Fractional doses of proton pump inhibitors (PPIs) more often than once daily (qd) inhibit 24-h acid secretion more effectively than an increase in the standard single daily dose. Although rabeprazole 5 mg qd is covered for prevention of aspirin-induced gastric injury under the Japanese insurance system, it is unclear whether rabeprazole 5 mg twice daily (bid) would more effectively inhibit acid secretion. We compared acid inhibition between rabeprazole 10 mg qd and 5 mg bid in healthy volunteers with different alleles of CYP2C19. METHODS Twelve Helicobacter pylori-negative healthy volunteers (CYP2C19 genotypes: extensive metabolizer (EM) (n = 6) and poor metabolizer (PM) (n = 6)) received three kinds of regimen for 7 days under a randomized crossover design: rabeprazole 5 mg qd (5 mg QD), 10 mg qd (10 mg QD), and 5 mg bid (5 mg BID). A 24-hour pH monitoring was conducted before the trial and on day 7 of each regimen. RESULTS No significant differences in median pH values (4.0 (1.9-5.9)) and (4.4 (2.1-6.5)) or percent time of pH ≥ 4 (50.7% (11.9-86.8%) and 56.8% (19.3-83.9%)) were seen between the 10 mg QD and 5 mg BID regimens. Median pHs and percent time of pH ≥ 4 in CYP2C19 PMs were significantly higher than those in EMs. With 5 mg BID, there was no significant difference in percent-time with pH ≥ 4 between daytime and nighttime, but the 10 mg QD showed a significant difference. CONCLUSION Rabeprazole 5 mg bid provided no therapeutic advantage for acid inhibition compared with rabeprazole 10 mg qd, regardless of CYP2C19 genotype status.
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Affiliation(s)
- Masaki Murata
- Department of Gastroenterology, National Hospital Organization, Kyoto Medical Center, Kyoto, 612-8555, Japan
| | - Mitsushige Sugimoto
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, 6-7-1, Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.
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Scheidl E, Benz C, Loeff P, Groneck V, König A, Schulte-Fischedick A, Lück H, Fuhr U. Frequency and Types of Pathological Upper Gastrointestinal Endoscopy Findings in Clinically Healthy Individuals. Drugs R D 2020; 20:115-124. [PMID: 32335854 PMCID: PMC7221033 DOI: 10.1007/s40268-020-00303-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND AND OBJECTIVE Beyond its application for diagnostics in patients, esophagogastroduodenoscopy (EGD) is used to assess gastrointestinal drug effects in clinical trials, where the interpretation of any pathological findings depends on the respective background variability. The objective of this analysis was to characterize the occurrence of pathological findings in the upper gastrointestinal tract in symptom-free healthy individuals. METHODS A baseline EGD was performed in clinically healthy individuals in three clinical trials aimed to assess gastrointestinal tolerability of drugs. Pathological findings were described by type (redness, erosion, ulcer or other), number, size and location, and by clinical relevance as assessed by the endoscopist. Characteristics of volunteers were tested as potential covariates. RESULTS A total of 294 EGDs were assessed. Characteristics of individuals were as follows: 257 (87.4%) males, age (mean ± SD) 32.0 ± 8.1 years, body weight 76.0 ± 10.6 kg, body mass index (BMI) 24.0 ± 2.5 kg/m2, 200 consumed alcohol, 250 (of 290 where this information was available) consumed caffeine and 39 (of 152) were smokers, 30 (of 151) tested positive for H. pylori. Any pathological finding was present in 79.6%. Clinically relevant findings occurred in 44.2%, mainly erosions (39.1%). Nine stomach ulcers were observed. Only age and BMI had a statistically significant relationship to overall pathological findings [age 3.4 years higher (p = 0.027), and BMI 1.6 kg/m2 higher (p < 0.001); for clinically relevant vs no findings]. CONCLUSION Upper gastrointestinal tract mucosal lesions, including those assessed as clinically relevant, are frequent in clinically healthy individuals, impeding the assessment of causality for both disease and drug effects on gastrointestinal health.
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Affiliation(s)
- Elisabeth Scheidl
- Clinical Pharmacology Unit, Department I of Pharmacology, Center for Pharmacology, University Hospital Cologne (AöR), Gleueler Straße 24, 50931, Köln, Germany
- ITECRA GmbH & Co. KG, Köln, Germany
| | - Claus Benz
- Department of Gastroenterology, Ev. Krankenhaus Köln-Weyertal, Köln, Germany
| | - Peter Loeff
- Department of Gastroenterology, Ev. Krankenhaus Köln-Weyertal, Köln, Germany
| | - Volker Groneck
- Department of Gastroenterology, Ev. Krankenhaus Köln-Weyertal, Köln, Germany
| | - Andreas König
- Department of Gastroenterology, Ev. Krankenhaus Köln-Weyertal, Köln, Germany
| | | | | | - Uwe Fuhr
- Clinical Pharmacology Unit, Department I of Pharmacology, Center for Pharmacology, University Hospital Cologne (AöR), Gleueler Straße 24, 50931, Köln, Germany.
- ITECRA GmbH & Co. KG, Köln, Germany.
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Masuda T, Yano F, Omura N, Tsuboi K, Hoshino M, Yamamoto SR, Akimoto S, Kashiwagi H, Yanaga K. Effect of Low-Dose Aspirin on Chronic Acid Reflux Esophagitis in Rats. Dig Dis Sci 2018; 63:72-80. [PMID: 29143196 DOI: 10.1007/s10620-017-4840-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2017] [Accepted: 11/06/2017] [Indexed: 12/23/2022]
Abstract
BACKGROUND Clinical role of low-dose aspirin (LDA) in pathogenesis of gastroesophageal reflux disease is by far controversial. This can be attributed to the paucity of basic research detailing the mechanism of LDA-induced esophageal mucosal injury (EI) on underlying chronic acid reflux esophagitis (RE). AIM The aim of this study was to clarify the effect of LDA on chronic RE in rats. METHODS Esophagitis was induced in 8-week-old male Wistar rats by ligating the border between forestomach and glandular portion with a 2-0 silk tie and covering the duodenum with a small piece of 18-Fr Nélaton catheter. Seventy-eight chronic RE rat models were divided into five treatment groups, consisting of orally administered vehicle (controls), and aspirin doses of 2, 5, 50 or 100 mg/kg once daily for 28 days. EI was assessed by gross area of macroscopic mucosal injury, severity grade of esophagitis and microscopic depth of infiltration by inflammatory cells. RESULTS Area of esophagitis in animals with aspirin dose of 100 mg/kg/day showed a 36.5% increase compared with controls, although it failed to achieve statistical significance (p = 0.812). Additionally, the rate of severe EI was increased in animals with aspirin dose of 100 mg/kg/day as compared with controls (p < 0.05). The grade of severity correlated with the depth of inflammation (r s = 0.492, p < 0.001). CONCLUSIONS Maximal dose aspirin (100 mg/kg/day) contributed in exacerbating preexisting EI. LDA (2 and 5 mg/kg/day), on the other hand, did not affect chronic RE in this model. LDA seems to be safe for use in patients with chronic RE.
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Affiliation(s)
- Takahiro Masuda
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishishinbashi, Minato-ku, Tokyo, 105-8461, Japan.
| | - Fumiaki Yano
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishishinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Nobuo Omura
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishishinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Kazuto Tsuboi
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishishinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Masato Hoshino
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishishinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Se Ryung Yamamoto
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishishinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Shunsuke Akimoto
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishishinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Hideyuki Kashiwagi
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishishinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Katsuhiko Yanaga
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishishinbashi, Minato-ku, Tokyo, 105-8461, Japan
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Kono Y, Okada H, Takenaka R, Miura K, Kanzaki H, Hori K, Kita M, Tsuzuki T, Kawano S, Kawahara Y, Yamamoto K. Does Helicobacter pylori Exacerbate Gastric Mucosal Injury in Users of Nonsteroidal Anti-Inflammatory Drugs? A Multicenter, Retrospective, Case-Control Study. Gut Liver 2016; 10:69-75. [PMID: 26087789 PMCID: PMC4694737 DOI: 10.5009/gnl14372] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Background/Aims The interaction between nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori remains controversial. We retrospectively investigated whether H. pylori infection exacerbates severe gastric mucosal injury among chronic NSAID users. Methods From January 2010 to December 2013, a total of 245 long-term NSAID (including low-dose aspirin) users who had undergone an esophagogastroduodenoscopy and had been evaluated for H. pylori infection were enrolled at Okayama University Hospital and Tsuyama Chuo Hospital. The degree of gastric mucosal injury was assessed according to the modified Lanza score (MLS). Severe gastric mucosal injury was defined as an MLS ≥4. Univariate and multivariate logistic regression analyses were performed. Results In the univariate analysis, age ≥75 years (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.3 to 4.2), H. pylori-positivity (OR, 2.0; 95% CI, 1.2 to 3.5), and the concomitant use of proton pump inhibitors (PPIs) (OR, 0.48; 95% CI, 0.26 to 0.86) were significantly associated with severe gastric mucosal injury. The multivariate analysis was adjusted by age and sex and demonstrated that H. pylori-positivity (OR, 1.8; 95% CI, 1.0 to 3.3) and the concomitant use of PPIs (OR, 0.53; 95% CI, 0.28 to 0.99) significantly contributed to severe gastric mucosal injury. Conclusions H. pylori infection exacerbates severe gastric mucosal injury among chronic NSAID users.
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Affiliation(s)
- Yoshiyasu Kono
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Hiroyuki Okada
- Department of Endoscopy, Okayama University Hospital, Okayama, Japan
| | - Ryuta Takenaka
- Department of Internal Medicine, Tsuyama Chuo Hospital, Okayama, Japan
| | - Ko Miura
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Hiromitsu Kanzaki
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Keisuke Hori
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Masahide Kita
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Takao Tsuzuki
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Seiji Kawano
- Department of Endoscopy, Okayama University Hospital, Okayama, Japan
| | - Yoshiro Kawahara
- Department of Endoscopy, Okayama University Hospital, Okayama, Japan
| | - Kazuhide Yamamoto
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
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Cossentini LA, Da Silva RV, Yamada-Ogatta SF, Yamauchi LM, De Almeida Araújo EJ, Pinge-Filho P. Aspirin treatment exacerbates oral infections by Trypanosoma cruzi. Exp Parasitol 2016; 164:64-70. [PMID: 26826555 DOI: 10.1016/j.exppara.2016.01.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2015] [Revised: 01/08/2016] [Accepted: 01/20/2016] [Indexed: 01/05/2023]
Abstract
Oral transmission of the protozoan parasite Trypanosoma cruzi, the etiological agent of Chagas disease, has been documented in Latin American countries. The reported cases of infection were due to the ingestion of contaminated fresh fruit, juices, or sugar cane juice. There have been few studies on the physiopathology of the disease in oral transmission cases. Gastritis is a common ailment that can be caused by poor dietary habits, intake of alcohol or other gastric irritants, bacterial infection, or by the widespread use of non-steroidal anti-inflammatory drugs (NSAIDs). This study investigated in a mouse model whether gastric mucosal injury, induced by aspirin, would affect the course of disease in animals infected with T. cruzi by the oral route. The CL14 and G strains of T. cruzi, both of low infectivity, were used. To this end, groups of BALB/c mice were treated during 5 days with aspirin (100 mg kg(-1)) before oral infection with T. cruzi metacyclic forms (4 × 10(5) or 5 × 10(7) parasites/mouse). Histological analysis and determination of nitric oxide and TNF-α were performed in gastric samples obtained 5 days after infection. Parasitemia was monitored from the thirteenth day after infection. The results indicate that aspirin treatment of mice injured their gastric mucosa and facilitated invasion by both CL14 and G strains of T. cruzi. Strain CL14 caused more severe infection compared to the G strain, as larger numbers of amastigote nests were found in the stomach and parasitemia levels were higher. Our study is novel in that it shows that gastric mucosal damage caused by aspirin, a commonly used NSAID, facilitates T. cruzi infection by the oral route.
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Affiliation(s)
- Luana Aparecida Cossentini
- Laboratório de Imunopatologia Experimental, Departamento de Ciências Patológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil
| | | | | | - Lucy Megumi Yamauchi
- Departamento de Microbiologia, Universidade Estadual de Londrina, Londrina, Paraná, Brazil
| | - Eduardo José De Almeida Araújo
- Laboratório de Neurogastroenterologia, Departamento de Histologia, Universidade Estadual de Londrina, Londrina, Paraná, Brazil
| | - Phileno Pinge-Filho
- Laboratório de Imunopatologia Experimental, Departamento de Ciências Patológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.
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10
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Iijima K, Shimosegawa T. Geographic differences in low-dose aspirin-associated gastroduodenal mucosal injury. World J Gastroenterol 2015; 21:7709-7717. [PMID: 26167071 PMCID: PMC4491958 DOI: 10.3748/wjg.v21.i25.7709] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2015] [Revised: 05/14/2015] [Accepted: 06/10/2015] [Indexed: 02/06/2023] Open
Abstract
Aspirin, even at low doses, has been known to cause upper gastro-intestinal complications, such as gastroduodenal ulcers, despite the definite benefits from its antithrombotic effects. Helicobacter pylori (H. pylori) is major pathogen responsible for gastroduodenal ulcer formation. There have been conflicting results about the potential interaction between these two ulcerogenic factors and the geographic areas involved. In Western countries, the prevalence of gastroduodenal ulcers is consistently higher in H. pylori-positive low-dose aspirin (LDA) users than in H. pylori-negative ones, suggesting that H. pylori infection exacerbates LDA-induced gastroduodenal mucosal injury in these geographic areas. Meanwhile, previous studies from Japan have generally reported a similar prevalence of LDA-induced gastroduodenal mucosal injury regardless of the presence of H. pylori infection, indicating that the infection is not an overall exacerbating factor for drug-induced injury. H. pylori infection could have a synergistic or antagonistic interaction with LDA use in adverse gastroduodenal events depending on gastric acid secretion. It is well-recognized that the net effect of H. pylori infection on gastric acid secretion shows considerable geographic variation at the population level. While gastric acid secretion levels were not decreased and were well-preserved in most patients with H. pylori infection from Western countries, the majority of Japanese patients with H. pylori infection exhibited decreased gastric acid secretion. Such large geographic differences in the net effect of H. pylori infection on gastric acid secretion could be at least partly responsible for the geographically distinct interaction between LDA use and H. pylori infection on adverse gastroduodenal lesions.
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11
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Fujishiro M, Higuchi K, Kato M, Kinoshita Y, Iwakiri R, Watanabe T, Takeuchi T, Sugisaki N, Okada Y, Ogawa H, Arakawa T, Fujimoto K, the PLANETARIUM Study Group. 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. J Clin Biochem Nutr 2015; 56:228-239. [PMID: 26060354 PMCID: PMC4454079 DOI: 10.3164/jcbn.15-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2015] [Accepted: 01/26/2015] [Indexed: 12/22/2022] Open
Abstract
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.
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Affiliation(s)
- Mitsuhiro Fujishiro
- Department of Endoscopy and Endoscopic Surgery, Graduate
School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655,
Japan
| | - Kazuhide Higuchi
- Second Department of Internal Medicine, Osaka Medical
College, 2-7 Daigaku-cho, Takatsuki, Osaka 569-8686, Japan
| | - Mototsugu Kato
- Division of Endoscopy, Hokkaido University Hospital, Nishi
5-chome, Kita 14-jou, Kita-ku, Sapporo, Hokkaido 060-8648, Japan
| | - Yoshikazu Kinoshita
- Department of Internal Medicine II, Faculty of Medicine,
Shimane University, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan
| | - Ryuichi Iwakiri
- Department of Internal Medicine & Gastrointestinal
Endoscopy, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan
| | - Toshio Watanabe
- Department of Gastroenterology, Osaka City University
Graduate School of Medicine, 1-5-7 Asahi-cho, Abeno-ku, Osaka 545-8586, Japan
| | - Toshihisa Takeuchi
- Second Department of Internal Medicine, Osaka Medical
College, 2-7 Daigaku-cho, Takatsuki, Osaka 569-8686, Japan
| | - Nobuyuki Sugisaki
- Clinical Development, Japan/Asia Clinical Research
Product Creation Unit, Eisai Product Creation Systems, Eisai Co., Ltd., 4-6-10
Koishikawa, Bunkyo-ku, Tokyo 112-8088, Japan
| | - Yasushi Okada
- Clinical Research Institute and Cerebrovascular Medicine,
National Hospital Organization, Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka
810-8563, Japan
| | - Hisao Ogawa
- Department of Cardiovascular Medicine, Graduate School of
Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556,
Japan
- National Cerebral and Cardiovascular Center, 5-7-1
Fujishiro-dai, Suita, Osaka, 565-8565, Japan
| | - Tetsuo Arakawa
- Department of Gastroenterology, Osaka City University
Graduate School of Medicine, 1-5-7 Asahi-cho, Abeno-ku, Osaka 545-8586, Japan
| | - Kazuma Fujimoto
- Department of Internal Medicine, Saga Medical School,
5-1-1 Nabeshima, Saga 849-8501, Japan
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12
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Iwakiri R, Higuchi K, Kato M, Fujishiro M, Kinoshita Y, Watanabe T, Takeuchi T, Yamauchi M, Sanomura M, Nakagawa H, Sugisaki N, Okada Y, Ogawa H, Arakawa T, Fujimoto K. Randomised clinical trial: prevention of recurrence of peptic ulcers by rabeprazole in patients taking low-dose aspirin. Aliment Pharmacol Ther 2014; 40:780-95. [PMID: 25100080 DOI: 10.1111/apt.12907] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2014] [Revised: 05/28/2014] [Accepted: 07/18/2014] [Indexed: 12/21/2022]
Abstract
BACKGROUND Few studies have evaluated the effects of rabeprazole on low-dose aspirin (LDA)-induced gastroduodenal injuries. AIM To conduct a randomised, double-blind, triple-dummy, active-controlled, multicentre trial, named the PLANETARIUM study, to assess the efficacy, dose-response relationship and safety of rabeprazole for peptic ulcer recurrence in Japanese patients on long-term LDA therapy. METHODS Eligible patients had a history of endoscopically confirmed peptic ulcers and were receiving long-term LDA (81 or 100 mg/day) therapy for cardiovascular or cerebrovascular protection. Subjects were randomly segregated into three groups receiving rabeprazole 10 mg once daily (standard dose in Japan), rabeprazole 5 mg once daily, or teprenone (geranylgeranylacetone; mucosal protective agent commercially available in Japan) 50 mg three times per day as an active control. The primary endpoint was recurrence of peptic ulcers over 24 weeks. RESULTS Among 472 randomised subjects, 452 subjects (n = 151, 150, 151, respectively) constituted the full analysis set. The cumulative recurrence rates of peptic ulcers over 24 weeks in the 10- and 5-mg rabeprazole groups were 1.4% and 2.8%, respectively, both of which were significantly lower than that in the teprenone group (21.7%). The cumulative occurrence rate of bleeding ulcers over 24 weeks in the teprenone group was 4.6%, while bleeding ulcers were not observed in the 10- or 5-mg rabeprazole groups. Rabeprazole was well tolerated at both doses. CONCLUSION Rabeprazole prevents the recurrence of peptic ulcers with no evidence of a major dose-response effect in subjects on low-dose aspirin therapy.
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Affiliation(s)
- R Iwakiri
- Department of Internal Medicine & Gastrointestinal Endoscopy, Saga Medical School, Saga, Japan
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13
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Sugimoto M, Shirai N, Nishino M, Kodaira C, Uotani T, Sahara S, Ichikawa H, Kagami T, Sugimoto K, Furuta T. Comparison of acid inhibition with standard dosages of proton pump inhibitors in relation to CYP2C19 genotype in Japanese. Eur J Clin Pharmacol 2014; 70:1073-1078. [PMID: 24996380 DOI: 10.1007/s00228-014-1713-y] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2014] [Accepted: 06/25/2014] [Indexed: 12/24/2022]
Abstract
INTRODUCTION The aim of therapeutic regimens using proton pump inhibitors (PPIs) in patients with acid-related diseases is to potently inhibit acid secretion for the full 24 h. However, optimum treatment is still unclear because the pharmacodynamics of PPIs differ among CYP2C19 genotypes and most of the previous studies have had loss of sample power. METHODS Using pH monitoring, we compared acid inhibition at standard dosage of omeprazole (20 mg, 50 times), lansoprazole (30 mg, 68 times), and rabeprazole (10 mg, 65 times) in Helicobacter pylori-negative healthy young Japanese volunteers. RESULTS Median pH with rabeprazole was 5.4 (3.3-7.5), which was significantly greater than with either omeprazole [4.4 (2.1-7.3)] or lansoprazole [4.8 (3.5-6.4)] (both P < 0.05). Median 24-h pH differed among the different CYP2C19 genotypes in all three PPIs. In CYP2C19 extensive metabolizers (EMs), the genotype that is refractory to PPI treatment, median pH with omeprazole, lansoprazole, and rabeprazole was 3.8 (2.1-4.4), 4.5 (3.5-5.3) and 4.8 (3.3-7.5), respectively. DISCUSSION Treatment with the selected PPIs at their standard dosages had difficulty maintaining acid inhibition for a full 24 h, especially in CYP2C19 EM. However, rabeprazole has the merit of less influence of CYP2C19 genotype compared with the other PPIs.
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Affiliation(s)
- Mitsushige Sugimoto
- First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan,
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14
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Uotani T, Sugimoto M, Nishino M, Ichikawa H, Sahara S, Yamade M, Iwaizumi M, Yamada T, Osawa S, Sugimoto K, Umemura K, Watanabe H, Miyajima H, Furuta T. Prevention of gastric mucosal injury induced by anti-platelet drugs by famotidine. J Clin Pharmacol 2014; 54:858-864. [PMID: 24615745 DOI: 10.1002/jcph.284] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2013] [Accepted: 03/03/2014] [Indexed: 01/11/2025]
Abstract
Anti-platelet drug-induced gastric mucosal injury correlates with intragastric pH. Our aim was to investigate prophylaxis effects of famotidine, one of the representative histamine-2 receptor antagonists (H2RA), on gastric mucosal injury induced by dual therapy with low-dose aspirin and clopidogrel in relation to Helicobacter pylori (H. pylori) infection and CYP2C19 genotypes. This study was conducted for 20 healthy Japanese volunteers (10 H. pylori-positive and 10-negative subjects) with 100 mg aspirin plus 75 mg clopidogrel (AC) once-daily dosing and AC plus 20 mg famotidine twice-daily dosing (ACH). Mucosal injury was endoscopically assessed on day 3 and 7 and 24-hour intragastric pH and antiplatelet-function test was performed on day 7. Median pH in ACH was similar between CYP2C19 extensive metabolizer (EM) and intermediate metabolizer (IM)/poor metabolizer (PM) and was significantly higher in H. pylori-positive than negative subjects (P < .05). Mucosal injury with ACH significantly decreased in both day 3 and 7 compared with AC, irrespective with H. pylori and CYP2C19 genotypes (P < .05). Although antiplatelet effect of clopidogrel in EM was significantly higher than that in IM/PM, the additional famotidine did not affect the effect. Anti-platelet drug-induced gastric injury was alleviated by famotidine without attenuation of anti-platelet functions irrespective of H. pylori and CYP2C19 genotypes.
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Affiliation(s)
- Takahiro Uotani
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
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15
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Sugimoto M, Uotani T, Furuta T. Does rebamipide prevent gastric mucosal injury in patients taking aspirin and clopidogrel? Dig Dis Sci 2014; 59:1671-1673. [PMID: 24711076 DOI: 10.1007/s10620-014-3145-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2014] [Accepted: 03/27/2014] [Indexed: 02/06/2023]
Affiliation(s)
- Mitsushige Sugimoto
- First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan,
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16
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Sugimoto M, Uotani T, Nishino M, Yamade M, Sahara S, Yamada T, Osawa S, Sugimoto K, Umemura K, Watanabe H, Miyajima H, Furuta T. Antiplatelet drugs are a risk factor for esophageal mucosal injury. Digestion 2013; 87:281-289. [PMID: 23774797 DOI: 10.1159/000350438] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2012] [Accepted: 02/27/2013] [Indexed: 02/04/2023]
Abstract
BACKGROUND In esophagus whether antiplatelet drugs, such as low-dose aspirin (LDA) and clopidogrel, induce mucosal injury by pH changes or by acid reflux is unclear. We designed to clarify which mechanism was responsible. METHODS In study 1, 80 patients taking LDA and 80 age- and sex-matched subjects who underwent endoscopy for dyspeptic symptoms or for a health check-up were evaluated the endoscopic incidence of esophageal mucosal injury and severity. In study 2, 35 healthy subjects were treated with LDA 100 mg (regimen A), and then 20 randomly selected subjects were dosed clopidogrel 75 mg (regimen C), LDA/clopidogrel (regimen AC), or LDA/clopidogrel/rabeprazole 10 mg for 7 days. Subjects underwent endoscopy and 24-hour pH measurements on day 7. RESULTS In study 1, the prevalence of esophageal injury in LDA patients was 40.0%, significantly higher than in non-LDA subjects (25.0%, p = 0.042). In study 2, significant increases in incidence of injury were observed with regimens A (45.8%) and AC (50.0%), but not with C (20.0%), on day 7. Among subjects in whom pH was >5.0 and <4.0 for less than 40% of time, none developed esophageal injury. CONCLUSIONS LDA caused esophageal injury in half of patients and volunteers. Acid-inhibitory drugs effectively prevented the development of LDA-induced, not clopidogrel, esophageal injury.
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Affiliation(s)
- Mitsushige Sugimoto
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
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Tamura A, Murakami K, Kadota J. Prevalence of gastroduodenal ulcers/erosions in patients taking low-dose aspirin with either 15 mg/day of lansoprazole or 40 mg/day of famotidine: the OITA-GF study 2. BMC Res Notes 2013; 6:116. [PMID: 23531145 PMCID: PMC3626555 DOI: 10.1186/1756-0500-6-116] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2012] [Accepted: 03/20/2013] [Indexed: 12/27/2022] Open
Abstract
Background The preventive effects of histamine 2 receptor antagonists vs. proton pump inhibitors on low-dose aspirin (LDA)-related gastroduodenal mucosal injury have not been fully investigated. We conducted a cross-sectional study to compare the prevalence of gastroduodenal ulcers or erosions in patients taking LDA with either 40 mg/day of famotidine or 15 mg/day of lansoprazole for at least three months. Methods Of 84 eligible patients, two taking 40 mg/day of famotidine and four taking 15 mg/day of lansoprazole refused to undergo upper gastrointestinal endoscopy. Ultimately, we performed upper gastrointestinal endoscopy in 78 patients taking either 40 mg/day of famotidine (group F, n = 31) or 15 mg/day of lansoprazole (group L, n = 47). The prevalence of gastroduodenal ulcers or erosions and the magnitude of gastric mucosal injury evaluated using modified Lanza scores were compared between the two groups. Results No patients in either group had gastroduodenal ulcers. Gastroduodenal erosions were more prevalent in group F than in group L (48.4% vs. 17.0%, p = 0.005). The modified Lanza scores (mean ± SD) were significantly higher in group F than in group L (0.9 ± 1.3 vs. 0.3 ± 0.7, p = 0.007). A multivariate logistic regression analysis showed that the use of lansoprazole was negatively associated with gastroduodenal erosions. Conclusions This study suggests that 15 mg/day of lansoprazole may be more effective in preventing the development of LDA-related gastroduodenal erosions than 40 mg/day of famotidine. The preventive effects of these two regimens on the development of LDA-related gastroduodenal ulcers require further investigation.
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Affiliation(s)
- Akira Tamura
- Internal Medicine 2, Oita University, Yufu, Japan.
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18
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Furuta T, Sugimoto M, Shirai N. Individualized therapy for gastroesophageal reflux disease: potential impact of pharmacogenetic testing based on CYP2C19. Mol Diagn Ther 2012. [PMID: 22873740 DOI: 10.2165/11634960-000000000-00000] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
The main therapeutic agent for gastroesophageal reflux disease (GERD) is a proton pump inhibitor (PPI). Plasma levels and the acid inhibitory effect of PPIs depend on the activity of cytochrome P450 (CYP) 2C19, which is polymorphic. Genotypes of CYP2C19 are classified into three groups: rapid metabolizers (RMs: *1/*1), intermediate metabolizers (IMs: *1/*X), and poor metabolizers (PMs: *X/*X), where *1 and X represent the wild type and the mutant allele, respectively. RMs include ultra-rapid metabolizers, who possess the CYP2C19*17 allele. The pharmacokinetics and pharmacodynamics of PPIs differ among different CYP2C19 genotype groups. Plasma PPI levels and intragastric pH values during PPI treatment are lowest in the RM group, intermediate in the IM group, and highest in the PM group. These CYP2C19-genotype-dependent differences in the pharmacokinetics and pharmacodynamics of PPIs influence the healing and recurrence of GERD during PPI treatment, suggesting the need for CYP2C19 genotype-based tailored therapy for GERD. CYP2C19 pharmacogenetics should be taken into consideration for the personalization of PPI-based therapy. However, the clinical usefulness of CYP2C19 genotype testing in GERD therapy should be verified in clinical studies.
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Affiliation(s)
- Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan.
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Sanuki T, Fujita T, Kutsumi H, Hayakumo T, Yoshida SI, Inokuchi H, Murakami M, Matsubara Y, Kuwayama H, Kawai T, Miyaji H, Fujisawa T, Terao S, Yamazaki Y, Azuma T. Rabeprazole reduces the recurrence risk of peptic ulcers associated with low-dose aspirin in patients with cardiovascular or cerebrovascular disease: a prospective randomized active-controlled trial. J Gastroenterol 2012; 47:1186-97. [PMID: 22526273 DOI: 10.1007/s00535-012-0588-x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2012] [Accepted: 03/19/2012] [Indexed: 02/04/2023]
Abstract
BACKGROUND Patients using low-dose aspirin (LDA) have an increased risk of gastroduodenal mucosal lesions and upper gastrointestinal symptoms. We aimed to clarify the efficacy of rabeprazole for preventing peptic ulcer, esophagitis, and gastrointestinal symptoms associated with LDA. METHODS Patients with a history of peptic ulcers who were receiving LDA for cardiovascular or cerebrovascular disease were randomly assigned to receive rabeprazole at 10 mg daily, rabeprazole at 20 mg daily, or gefarnate (a cytoprotective anti-ulcer agent) at 50 mg twice daily. The primary endpoint was the development of gastric and/or duodenal ulcer at 12 weeks. The modified Lanza score (MLS) and gastrointestinal symptoms were evaluated at baseline and at 12 weeks. RESULTS The full analysis set comprised 261 patients (rabeprazole 10 mg: n = 87, rabeprazole 20 mg: n = 89, gefarnate 100 mg: n = 85). The cumulative incidences of gastroduodenal ulcers at 12 weeks in the 10 mg rabeprazole group, 20 mg rabeprazole group, and gefarnate group were 7.4, 3.7, and 26.7 %, respectively (rabeprazole group 5.5 % vs. gefarnate group 26.7 %, hazard ratio [HR] 0.179; 95 % confidence interval [CI] 0.082-0.394; p < 0.0001). The proportions of patients with an MLS of ≥1 and erosive esophagitis were significantly lower in the rabeprazole group than in the gefarnate group at 12 weeks (gastric lesions 33.5 vs. 62.4 %, p < 0.0001; duodenal lesions 5.7 vs. 24.7 %, p < 0.0001; erosive esophagitis 5.8 vs. 19.4 %, p < 0.0001). Rabeprazole was significantly more effective than gefarnate for the resolution and prevention of gastrointestinal symptoms (resolution 53.6 vs. 25.0 %, p = 0.017; occurrence 9.2 vs. 28.3 %, p = 0.0026). CONCLUSIONS Rabeprazole is more effective than gefarnate for reducing the risk of recurrence of peptic ulcer, esophagitis, and gastrointestinal symptoms in LDA users.
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Affiliation(s)
- Tsuyoshi Sanuki
- Department of Gastroenterology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
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20
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Sugimoto M, Shirai N, Nishino M, Kodaira C, Uotani T, Yamade M, Sahara S, Ichikawa H, Sugimoto K, Miyajima H, Furuta T. Rabeprazole 10 mg q.d.s. decreases 24-h intragastric acidity significantly more than rabeprazole 20 mg b.d. or 40 mg o.m., overcoming CYP2C19 genotype. Aliment Pharmacol Ther 2012; 36:627-634. [PMID: 22882464 DOI: 10.1111/apt.12014] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2012] [Revised: 06/26/2012] [Accepted: 07/20/2012] [Indexed: 12/14/2022]
Abstract
BACKGROUND Standard dosing (i.e. once daily) of proton pump inhibitors (PPIs) cannot inhibit acid secretion for a full 24 h. Better therapeutic regimens using PPIs are required to sustain potent acid inhibition for the full 24 h in all patients with acid-related diseases. AIM To evaluate acid inhibitory effects by different dosing times of a PPI at the same daily dosage, in a study involving 70 rounds of pH monitoring. METHODS Using pH monitoring, we evaluated the efficacy of different divided treatment regimens with the same total daily dose of rabeprazole (40 mg o.m., 15 rounds; 20 mg b.d., 20 rounds; 10 mg q.d.s., 35 rounds) on day 7 or 8 of PPI dosing. RESULTS In the study of divided treatment, the median pH (when administered once, twice or four times to achieve a daily dose of 40 mg) was 4.8 (3.6-6.4), 5.7 (4.1-7.4), 6.6 (4.9-8.4), respectively. When comparing the median pHs at the same CYP2C19 genotype among different dosing times of rabeprazole, the median pH attained with 10 mg q.d.s. was significantly higher than that in 40 mg o.m. or 20 mg b.d. Increase in the frequency of dosing effectively increased pH [median percent time of pH > 4.0 with q.d.s. therapy: 95.5% (63.2-100.0%)], irrespective to CYP2C19 genotype. CONCLUSION Four times daily dosing with rabeprazole 10 mg achieved potent acid inhibition, including during the night-time, suggesting its potential usefulness as a regimen for patients who are refractory to standard once daily PPI treatment.
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Affiliation(s)
- M Sugimoto
- First Department of Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan.
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21
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Furuta T, Sugimoto M, Shirai N. Individualized therapy for gastroesophageal reflux disease: potential impact of pharmacogenetic testing based on CYP2C19. Mol Diagn Ther 2012; 16:223-234. [PMID: 22873740 DOI: 10.1007/bf03262211] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The main therapeutic agent for gastroesophageal reflux disease (GERD) is a proton pump inhibitor (PPI). Plasma levels and the acid inhibitory effect of PPIs depend on the activity of cytochrome P450 (CYP) 2C19, which is polymorphic. Genotypes of CYP2C19 are classified into three groups: rapid metabolizers (RMs: *1/*1), intermediate metabolizers (IMs: *1/*X), and poor metabolizers (PMs: *X/*X), where *1 and X represent the wild type and the mutant allele, respectively. RMs include ultra-rapid metabolizers, who possess the CYP2C19*17 allele. The pharmacokinetics and pharmacodynamics of PPIs differ among different CYP2C19 genotype groups. Plasma PPI levels and intragastric pH values during PPI treatment are lowest in the RM group, intermediate in the IM group, and highest in the PM group. These CYP2C19-genotype-dependent differences in the pharmacokinetics and pharmacodynamics of PPIs influence the healing and recurrence of GERD during PPI treatment, suggesting the need for CYP2C19 genotype-based tailored therapy for GERD. CYP2C19 pharmacogenetics should be taken into consideration for the personalization of PPI-based therapy. However, the clinical usefulness of CYP2C19 genotype testing in GERD therapy should be verified in clinical studies.
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Affiliation(s)
- Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan.
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22
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Kim Y, Yokoyama S, Watari J, Hori K, Yamasaki T, Okugawa T, Toyoshima F, Kondo T, Sakurai J, Tanaka J, Tomita T, Oshima T, Fukui H, Abe T, Matsumoto T, Miwa H. Endoscopic and clinical features of gastric ulcers in Japanese patients with or without Helicobacter pylori infection who were using NSAIDs or low-dose aspirin. J Gastroenterol 2012; 47:904-11. [PMID: 22350702 DOI: 10.1007/s00535-012-0553-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2011] [Accepted: 01/31/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND The endoscopic characteristics of gastric ulcers in patients who were using non-steroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin (LDA) and were infected with Helicobacter pylori remain unclear. We elucidated the endoscopic characteristics of gastric ulcers that occurred in the presence or absence of H. pylori infection and were associated with the use of these drugs. METHODS A total of 379 patients with active-stage gastric ulcer were divided into three groups: H. pylori-positive patients using neither NSAIDs nor LDA (control group, n = 216), H. pylori-positive or -negative patients using NSAIDs (NSAIDs group, n = 100), and H. pylori-positive or -negative patients using LDA (LDA group, n = 63). The differences among these groups in endoscopic characteristics of the ulcers (site, multiplicity, and morphology) were determined. The influence of an antacid drug, i.e., a proton pump inhibitor (PPI) or a histamine H(2) receptor antagonist (H(2)RA), was also investigated. RESULTS The NSAIDs group, regardless of H. pylori infection status, had higher incidences of antral, multiple, and irregularly shaped ulcers. The LDA group had a higher incidence of antral ulcers in H. pylori-negative patients and, regardless of H. pylori infection status, a higher incidence of multiple ulcers. However, the incidence of irregularly shaped ulcers in the LDA group did not differ from that in the control group. Neither the concomitant use of an antacid nor the dosing period of NSAIDs affected the results. CONCLUSIONS Our study elucidated the morphological characteristics of gastric ulcers in persons taking NSAIDs or LDA in the presence and absence of H. pylori infection. Our results may be clinically useful for inferring the causes of ulcers from their morphological characteristics.
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Affiliation(s)
- Yongmin Kim
- Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
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23
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Uotani T, Sugimoto M, Nishino M, Kodaira C, Yamade M, Sahara S, Yamada T, Osawa S, Sugimoto K, Tanaka T, Umemura K, Watanabe H, Miyajima H, Furuta T. Ability of rabeprazole to prevent gastric mucosal damage from clopidogrel and low doses of aspirin depends on CYP2C19 genotype. Clin Gastroenterol Hepatol 2012; 10:879-885.e2. [PMID: 22542748 DOI: 10.1016/j.cgh.2012.04.016] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2011] [Revised: 03/22/2012] [Accepted: 04/11/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Low doses of aspirin can injure the gastric mucosa. It is not clear whether other drugs such as the antiplatelet agent clopidogrel also cause gastric mucosal injury or exacerbate aspirin-induced injury, or whether proton pump inhibitors prevent damage. METHODS Twenty Japanese subjects with different CYP2C19 genotypes were randomly assigned to groups that were given a low dose of aspirin (100 mg; A), clopidogrel (75 mg; C), low dose of aspirin and clopidogrel (AC), or low dose of aspirin in combination with clopidogrel and rabeprazole (10 mg; ACR) once daily for 7 days. Subjects underwent gastroduodenoscopy and platelet tests on days 3 and 7; gastric mucosal damage was assessed by using the modified Lanza score (MLS). We performed 24-hour intragastric pH monitoring on day 7 of each regimen. We also analyzed the effects of the AC regimen on 30 patients with different CYP2C19 genotypes. RESULTS Subjects in groups A, C, and AC had significantly higher levels of gastric mucosal damage on days 3 and 7, compared with baseline. The median MLS for the AC group was similar to that of the A group. Helicobacter pylori-negative subjects in the ACR group with different CYP2C19 genotypes had significant differences in MLS, intragastric pH, and platelet function. Gastric mucosal injury was inhibited equally among H pylori-positive subjects in the ACR group. Rabeprazole did not appear to affect platelet function or intragastric pH in subjects given clopidogrel. CONCLUSIONS Clopidogrel and low doses of aspirin cause a similar degree of gastric mucosal damage. Rabeprazole prevented this damage without reducing the antiplatelet function of clopidogrel. However, its prophylactic effect varies with CYP2C19 genotype in H pylori-negative subjects.
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Affiliation(s)
- Takahiro Uotani
- First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Japan
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24
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Sugimoto M, Jang JS, Yoshizawa Y, Osawa S, Sugimoto K, Sato Y, Furuta T. Proton Pump Inhibitor Therapy before and after Endoscopic Submucosal Dissection: A Review. DIAGNOSTIC AND THERAPEUTIC ENDOSCOPY 2012; 2012:791873. [PMID: 22851882 PMCID: PMC3407608 DOI: 10.1155/2012/791873] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/13/2012] [Accepted: 05/23/2012] [Indexed: 02/07/2023]
Abstract
Endoscopic submucosal dissection (ESD) is a novel endoscopic procedure first developed in the 1990s which enables en bloc resection of gastric neoplastic lesions that are difficult to resect via conventional endoscopic mucosal resection. However, given that ESD increases the risk of intra- and post-ESD delayed bleeding and that platelet aggregation and coagulation in artificial ulcers after ESD strongly depend on intragastric pH, faster and stronger acid inhibition via proton pump inhibitors (PPIs) and histamine 2-receptor antagonists (H(2)RAs) as well as endoscopic hemostasis by thermocoagulation during ESD have been used to prevent ESD-related bleeding. Because PPIs more potently inhibit acid secretion than H(2)RAs, they are often the first-line drugs employed in ESD treatment. However, acid inhibition after the initial infusion of a PPI is weaker in the early phase than that achievable with H(2)RAs; further, PPI effectiveness can vary depending on genetic differences in CYP2C19. Therefore, optimal acid inhibition may require tailored treatment based on CYP2C19 genotype when ESD is performed, with a concomitant infusion of PPI and H(2)RA possibly most effective for patients with the rapid metabolizer CYP2C19 genotype, while PPI alone may be sufficient for those with the intermediate or poor metabolizer genotypes.
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Affiliation(s)
- Mitsushige Sugimoto
- First Department of Medicine, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu 431-3192, Japan
| | - Jin Seok Jang
- Department of Gastroenterology, College of Medicine, Dong-A University, Busan 602-715, Republic of Korea
| | - Yashiro Yoshizawa
- Department of Gastroenterology, Seirei General Hospital, Naka-ku, Hamamatsu 430-8558, Japan
| | - Satoshi Osawa
- First Department of Medicine, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu 431-3192, Japan
- Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu 431-3192, Japan
| | - Ken Sugimoto
- First Department of Medicine, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu 431-3192, Japan
| | - Yoshihiko Sato
- Department of Gastroenterology, Seirei General Hospital, Naka-ku, Hamamatsu 430-8558, Japan
| | - Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu 431-3192, Japan
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25
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Fukuzawa M, Kawai T, Watanabe M, Tomiyama H, Yamashina A, Moriyasu F. Correlation between Helicobacter pylori infection and low-dose aspirin use on damage of the upper gastrointestinal tract. J Gastroenterol Hepatol 2012; 27 Suppl 3:76-81. [PMID: 22486876 DOI: 10.1111/j.1440-1746.2012.07077.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
BACKGROUND AND AIM Low-dose aspirin (LDA), and Helicobacter pylori (HP) infection are considered the two primary causes of peptic ulceration. The interaction between HP infection and non-steroidal anti-inflammatory drugs is, however, a matter of considerable discussion and controversy. In this study, we investigated possible synergistic or negative interactions between HP infection and LDA in gastric mucosal lesions, according to lesion site. METHODS The subjects were 120 patients attending the Cardiology Outpatients Department (average age, 67.1 ± 8.9 years; male : female ratio 2.9:1). Endoscopic findings were graded using the Modified Lanza score. Lesions were scored for the antral, body and fundal regions. Ulcers were defined as mucosal defects ≥ 5 mm in size. RESULTS There were 55 HP-positive and 65 HP-negative subjects, and 91 subjects on LDA therapy. The gastric antral Lanza scores were HP(-) LDA(-): 0.2 ± 1.6, HP(-) LDA(+): 1.8 ± 1.5, HP(+) LDA(-): 0.3 ± 0.7, and HP(+) LDA(+): 0.5 ± 1.0. The gastric body and fundal Lanza scores were 0.0 ± 0.0, 0.8 ± 0.9, 0.4 ± 1.1, and 1.0 ± 1.5, respectively, and 0.1 ± 0.3, 0.5 ± 0.9, 0.1 ± 0.3, and 0.1 ± 0.3, respectively. Variance analysis of the correlation between HP infection and LDA by regional Lanza scores identified both HP infection and LDA use as factors that significantly influence the antral Lanza score. However, LDA was an aggressive factor, and HP infection a protective factor. In the gastric body, LDA was a non-significant, and HP infection a significant, aggressive factor. In the gastric fundus, neither HP infection nor LDA was a significant factor (LDA was an aggressive factor, and HP infection a protective factor). CONCLUSIONS LDA had aggressive effects in all gastric lesions; on the other hand, HP infection had protective effects in the antrum and fundus in the stomach, and aggressive effects in the body in the stomach.
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Affiliation(s)
- Mari Fukuzawa
- Endoscopy Center, Tokyo Medical University Hospital, Tokyo, Japan
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Abstract
The presence of gastric acid plays a critical role in the mechanisms of NSAIDs/aspirin-associated gastric and duodenal mucosal injury and ulceration. The role of gastric acid and its relationship to NSAIDs/aspirin in mucosal damage, ulcer and ulcer complications continues to be an important concern because of the increasing worldwide use of NSAIDs and aspirin. Acid suppression continues to be an important prevention strategy for NSAID-associated gastric and duodenal ulcer and ulcer complications. While a coxib or an NSAID and PPI in combination are considered to have comparable safety profiles, the evidence from direct comparisons in high-risk patients is limited, and the cardiovascular safety of coxibs and NSAIDs remains a concern especially in patients with a high risk of cardiovascular disease. An evaluation of individual gastrointestinal and cardiovascular risks and benefits, selection of the most appropriate NSAID and dose for each particular patient should always be emphasized. Twice daily PPI is more appropriate to protect a patient who is taking NSAIDs twice daily. PPI co-therapy is still recommended in patients receiving dual antiplatelet treatment, although conflicting results have been reported about adverse drug interactions between PPIs and clopidogrel.
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Affiliation(s)
- Richard H Hunt
- Farncombe Family Digestive Health Research Institute, Division of Gastroenterology, McMaster University Health Science Centre, Hamilton, Ont., Canada.
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27
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Nakamura H, Yokoyama H, Yaguchi T, Suzuki Y, Tokuoka K, Watanabe M, Kitagawa Y, Yamada Y. [Investigation into the effect of gastric secretion inhibitor for the prevention of upper gastrointestinal lesions associated with low-dose aspirin]. YAKUGAKU ZASSHI 2011; 131:445-52. [PMID: 21372542 DOI: 10.1248/yakushi.131.445] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
In this study, we investigated the effect of histamin H₂ receptor antagonist (H₂RA) or proton pump inhibitor (PPI) for the prevention of upper gastrointestinal lesions associated with low-dose aspirin. We carried out a retrospective study of 2811 patients who had been prescribed low-dose aspirin (Bayaspirin® 100 mg) for more than 30 days at Tokai University Hachioji Hospital from 2006 to 2008. We classified them into three groups: aspirin alone group (n=1103), aspirin with H₂RA group (n=844) and aspirin with PPI group (n=864). Patients who developed upper gastrointestinal lesions were diagnosed with gastric ulcer, duodenal ulcer, gastritis or duodenitis by gastroscopy. We then compared the incidence of upper gastrointestinal lesions among the groups. The incidence in aspirin alone group, aspirin with H₂RA group and aspirin with PPI group was 2.54%, 1.54% and 1.04%, respectively; that of aspirin with PPI group being significantly lower (p<0.05). Additively, the odds ratio (OR) of aspirin with H₂RA group and aspirin with PPI group was 0.60 (95% confidence interval [95%CI]: 0.31-1.17) and 0.40 (95% CI: 0.19-0.86) as compared with aspirin alone group, respectively. The upper gastrointestinal lesions were developed within two years in all groups. Our results suggest that the combined administration of low-dose aspirin and PPI is effective for the prevention of upper gastrointestinal lesions associated with low-dose aspirin. Also, the pharmacists should be especially careful for upper gastrointestinal lesions development within two years after administration of low-dose aspirin, regardless of combined whether H₂RA or PPI.
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Affiliation(s)
- Hironori Nakamura
- Department of Clinical Evaluation of Drug Efficacy, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
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28
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Nishino M, Sugimoto M, Kodaira C, Yamade M, Uotani T, Shirai N, Ikuma M, Tanaka T, Sugimura H, Hishida A, Furuta T. Preventive effects of lansoprazole and famotidine on gastric mucosal injury induced by low-dose aspirin in Helicobacter pylori-negative healthy volunteers. J Clin Pharmacol 2011; 51:1079-1086. [PMID: 20663999 DOI: 10.1177/0091270010376194] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
The preventive effects of lansoprazole and famotidine on low-dose aspirin-induced gastric mucosal injury in relation to gastric acidity were compared in healthy Japanese volunteers. Fifteen Helicobacter pylori-negative volunteers with different CYP2C19 genotypes were randomly administered aspirin 100 mg, aspirin plus famotidine 20 mg twice daily, or aspirin plus lansoprazole 15 mg once daily for 7 days each in a crossover fashion. Gastroscopy for the evaluation of mucosal injury based on modified Lanza score (MLS) and 24-hour intragastric pH monitoring were performed on day 7 of each regimen. Aspirin induced gastric mucosal injury (median MLS = 3). Lansoprazole significantly decreased MLS to 0, which was significantly lower than that by famotidine (MLS = 1) (P < .05). Medians of pH 3 holding time and mean 24-hour pH values with the lansoprazole regimen were significantly higher than those with famotidine (P < .05). No significant differences in MLS were observed among the different CYP2C19 genotype groups in any of the treatment regimens. In this 7-day study, lansoprazole appeared to be more protective than famotidine against low-dose aspirin-induced mucosal injury but a larger well-controlled study is necessary to establish a definitive clinical benefit.
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Affiliation(s)
- Masafumi Nishino
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
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