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Vakil N. Peptic Ulcer Disease: A Review. JAMA 2024; 332:1832-1842. [PMID: 39466269 DOI: 10.1001/jama.2024.19094] [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: 10/29/2024]
Abstract
Importance In the US, peptic ulcer disease affects 1% of the population and approximately 54 000 patients are admitted to the hospital annually for bleeding peptic ulcers. Observations Approximately 10% of patients presenting with upper abdominal pain in a primary care setting have a peptic ulcer as the cause of their symptoms. The principal causes of peptic ulcer disease are Helicobacter pylori infection, which affects approximately 42% of patients with peptic ulcer disease, and aspirin or nonsteroidal anti-inflammatory drug (NSAID) use, which are etiologic factors in approximately 36% of people with peptic ulcer disease. Complications of peptic ulcer include bleeding (73% of patients), perforation (9% of patients), and pyloric obstruction (3% of patients). Annually, 10 000 people die of peptic ulcer disease in the US. Endoscopy definitively diagnoses peptic ulcer disease. Acid blockers, such as omeprazole, can heal peptic ulcers in approximately 80% to 100% of patients within 4 weeks, but gastric ulcers larger than 2 cm may require 8 weeks of treatment. Eradication of H pylori decreases peptic ulcer recurrence rates from approximately 50% to 60% to 0% to 2%. Discontinuing NSAIDs heals 95% of ulcers identified on endoscopy and reduces recurrence from 40% to 9%. When discontinuing an NSAID is not desirable, changing the NSAID (eg, from ketorolac to ibuprofen), adding a proton pump inhibitor such as omeprazole or lansoprazole, and eradicating H pylori with treatment such as bismuth, metronidazole, and tetracycline combined with omeprazole can reduce recurrence rates. Conclusions and Relevance Peptic ulcer disease is associated with increased hospitalization rates and mortality. Acid blocking with proton pump inhibitors, such as omeprazole or lansoprazole, is the primary treatment. Recurrence of ulcers can be prevented by eradicating H pylori if present and discontinuing aspirin or NSAIDs if applicable.
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Affiliation(s)
- Nimish Vakil
- University of Wisconsin School of Medicine and Public Health, Madison
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Weng J, Song Y, Kuai D, Dai W, Yao Y, Xu W, Li Y, Fan L, Xu B. Omeprazole taken once every other day can effectively prevent aspirin-induced gastrointestinal mucosal damage in rats. BMC Gastroenterol 2024; 24:187. [PMID: 38811868 PMCID: PMC11134753 DOI: 10.1186/s12876-024-03265-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Accepted: 05/15/2024] [Indexed: 05/31/2024] Open
Abstract
BACKGROUND Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such as gastric polyps and enterochromaffin-like cell hyperplasia. Current research indicates that the abovementioned adverse reactions are mainly related to hypergastrinemia. We investigated whether low-frequency administration of omeprazole could effectively repair aspirin-induced mucosal damage and reduce the increase in gastrin levels associated with long-term use of PPIs. METHODS Sprague‒Dawley rats were divided into four treatment groups: daily aspirin, daily aspirin and omeprazole once every day (qd), daily aspirin and omeprazole once every other day (qod), and daily aspirin and omeprazole once every three days (1/d3). After 15 days of feeding, blood samples were collected, and the stomachs of sacrificed rats were subjected to macroscopic, histological, and immunohistochemical studies. Moreover, in clinical practice, patients with peptic ulcers caused by aspirin took a standard dose of omeprazole (20 mg) every other day. Two months later, gastroscopy was performed to examine the healing of the ulcers. RESULTS Both the omeprazole qd and omeprazole qod administrations effectively prevented aspirin-induced gastric peptic ulcers, with no significant difference between the two groups in the inhibition of parietal cell secretion of gastric acid and cell apoptosis. However, omeprazole 1/d3 failed to completely prevent aspirin-induced gastric mucosal injury. Notably, the gastrin levels, cell proliferation ability and cholecystokinin B receptor expression of the omeprazole qd group were significantly higher than those of the omeprazole qod group. In clinical work, patients with peptic ulcers caused by aspirin were given a standard dose of omeprazole every other day, and their ulcers healed after 2 months, as observed by gastroscopy. CONCLUSIONS Omeprazole administration once every other day can effectively prevent aspirin-induced peptic ulcers and reduce hypergastrinemia, which may reduce the long-term adverse effects of PPI treatment.
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Affiliation(s)
- Junhua Weng
- Department of Gastroenterology, Beijing Lu He Hospital, Capital Medical University, 82 Xinhua South Road, Beijing, 101149, P.R. China
| | - Yuli Song
- Department of Gastroenterology, Beijing Lu He Hospital, Capital Medical University, 82 Xinhua South Road, Beijing, 101149, P.R. China
| | - Dayu Kuai
- Department of Gastroenterology, Beijing Lu He Hospital, Capital Medical University, 82 Xinhua South Road, Beijing, 101149, P.R. China
| | - Weiwei Dai
- Department of Gastroenterology, Beijing Lu He Hospital, Capital Medical University, 82 Xinhua South Road, Beijing, 101149, P.R. China
| | - Yuxia Yao
- Department of Gastroenterology, Beijing Lu He Hospital, Capital Medical University, 82 Xinhua South Road, Beijing, 101149, P.R. China
| | - Wenjing Xu
- Department of Gastroenterology, Beijing Lu He Hospital, Capital Medical University, 82 Xinhua South Road, Beijing, 101149, P.R. China
| | - Yaqiang Li
- Department of Gastroenterology, Beijing Lu He Hospital, Capital Medical University, 82 Xinhua South Road, Beijing, 101149, P.R. China
| | - Longying Fan
- Department of Gastroenterology, Beijing Lu He Hospital, Capital Medical University, 82 Xinhua South Road, Beijing, 101149, P.R. China
| | - Baohong Xu
- Department of Gastroenterology, Beijing Lu He Hospital, Capital Medical University, 82 Xinhua South Road, Beijing, 101149, P.R. China.
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Fischbach W, Bornschein J, Hoffmann JC, Koletzko S, Link A, Macke L, Malfertheiner P, Schütte K, Selgrad DM, Suerbaum S, Schulz C. Update S2k-Guideline Helicobacter pylori and gastroduodenal ulcer disease of the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:261-321. [PMID: 38364851 DOI: 10.1055/a-2181-2225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/18/2024]
Affiliation(s)
| | - Jan Bornschein
- Translational Gastroenterology Unit John, John Radcliffe Hospital Oxford University Hospitals, Oxford, United Kingdom
| | - Jörg C Hoffmann
- Medizinische Klinik I, St. Marien- und St. Annastiftskrankenhaus, Ludwigshafen, Deutschland
| | - Sibylle Koletzko
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU-Klinikum Munich, Munich, Deutschland
- Department of Paediatrics, Gastroenterology and Nutrition, School of Medicine Collegium Medicum University of Warmia and Mazury, 10-719 Olsztyn, Poland
| | - Alexander Link
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Magdeburg, Magdeburg, Deutschland
| | - Lukas Macke
- Medizinische Klinik und Poliklinik II Campus Großhadern, Universitätsklinikum Munich, Munich, Deutschland
- Deutsches Zentrum für Infektionsforschung, Standort Munich, Munich, Deutschland
| | - Peter Malfertheiner
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Magdeburg, Magdeburg, Deutschland
- Medizinische Klinik und Poliklinik II Campus Großhadern, Universitätsklinikum Munich, Munich, Deutschland
| | - Kerstin Schütte
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Niels-Stensen-Kliniken Marienhospital Osnabrück, Osnabrück, Deutschland
| | - Dieter-Michael Selgrad
- Medizinische Klinik Gastroenterologie und Onkologie, Klinikum Fürstenfeldbruck, Fürstenfeldbruck, Deutschland
- Klinik für Innere Medizin 1, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Sebastian Suerbaum
- Universität Munich, Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Munich, Deutschland
- Nationales Referenzzentrum Helicobacter pylori, Pettenkoferstr. 9a, 80336 Munich, Deutschland
- Deutsches Zentrum für Infektionsforschung, Standort Munich, Munich, Deutschland
| | - Christian Schulz
- Medizinische Klinik und Poliklinik II Campus Großhadern, Universitätsklinikum Munich, Munich, Deutschland
- Deutsches Zentrum für Infektionsforschung, Standort Munich, Munich, Deutschland
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Wang W, Song L, Yang L, Li C, Ma Y, Xue M, Shi D. Panax quinquefolius saponins combined with dual antiplatelet therapy enhanced platelet inhibition with alleviated gastric injury via regulating eicosanoids metabolism. BMC Complement Med Ther 2023; 23:289. [PMID: 37596586 PMCID: PMC10436642 DOI: 10.1186/s12906-023-04112-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Accepted: 08/01/2023] [Indexed: 08/20/2023] Open
Abstract
BACKGROUND Panax quinquefolius saponin (PQS) was shown beneficial against platelet adhesion and for gastroprotection. This study aimed to investigate the integrated efficacy of PQS with dual antiplatelet therapy (DAPT) on platelet aggregation, myocardial infarction (MI) expansion and gastric injury in a rat model of acute MI (AMI) and to explore the mechanism regarding arachidonic acid (AA)-derived eicosanoids metabolism. METHODS Wistar rats were subjected to left coronary artery occlusion to induce AMI model followed by treatment with DAPT, PQS or the combined therapy. Platelet aggregation was measured by light transmission aggregometry. Infarct size, myocardial histopathology was evaluated by TTC and H&E staining, respectively. Gastric mucosal injury was examined by scanning electron microscope (SEM). A comprehensive eicosanoids profile in plasma and gastric mucosa was characterized by liquid chromatography-mass spectrometer-based lipidomic analysis. RESULTS PQS+DAPT further decreased platelet aggregation, lessened infarction and attenuated cardiac injury compared with DAPT. Plasma lipidomic analysis revealed significantly increased synthesis of epoxyeicosatrienoic acid (EET) and prostaglandin (PG) I2 (potent inhibitors for platelet adhesion and aggregation) while markedly decreased thromboxane (TX) A2 (an agonist for platelet activation and thrombosis) by PQS+DAPT, relative to DAPT. DAPT induced overt gastric mucosal damage, which was attenuated by PQS co-administration. Mucosal gastroprotective PGs (PGE2, PGD2 and PGI2) were consistently increased after supplementation of PQS+DAPT. CONCLUSIONS Collectively, PQS+DAPT showed synergistic effect in platelet inhibition with ameliorated MI expansion partially through upregulation of AA/EET and AA/PGI2 synthesis while suppression of AA/TXA2 metabolism. PQS attenuated DAPT-induced gastric injury, which was mechanistically linked to increased mucosal PG production.
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Affiliation(s)
- Wenting Wang
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China
- Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Lei Song
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China
- Center of Cardiovascular Disease, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China
| | - Lin Yang
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China
- Center of Cardiovascular Disease, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China
| | - Changkun Li
- Shimadzu (China) Co., LTD Beijing Branch, Beijing, 100020, China
| | - Yan Ma
- Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology & Immunology, Vienna General Hospital, Medical University of Vienna, 1090, Vienna, Austria
| | - Mei Xue
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
- Center of Cardiovascular Disease, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
| | - Dazhuo Shi
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
- Center of Cardiovascular Disease, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
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Autoren, Collaborators:. Aktualisierte S2k-Leitlinie Helicobacter
pylori und gastroduodenale Ulkuskrankheit der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – Juli 2022 – AWMF-Registernummer: 021–001. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:544-606. [PMID: 37146633 DOI: 10.1055/a-1975-0414] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/07/2023]
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Masuda S, Muramatsu T, Ishibashi Y, Kozuma K, Tanabe K, Nakatani S, Kogame N, Nakamura M, Asano T, Okamura T, Miyazaki Y, Tateishi H, Ozaki Y, Nakazawa G, Morino Y, Katagiri Y, Garg S, Hara H, Ono M, Kawashima H, Lemos PA, Serruys PW, Onuma Y. Reduced-dose prasugrel monotherapy without aspirin after PCI with the SYNERGY stent in East Asian patients presenting with chronic coronary syndromes or non-ST-elevation acute coronary syndromes: rationale and design of the ASET Japan pilot study. ASIAINTERVENTION 2023; 9:39-48. [PMID: 36936091 PMCID: PMC10018289 DOI: 10.4244/aij-d-22-00033] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Accepted: 09/01/2022] [Indexed: 06/18/2023]
Abstract
The Acetyl Salicylic Elimination Trial (ASET) Japan pilot study is a multicentre, single-arm, open-label, proof-of-concept study with a stopping rule based on the occurrence of definite stent thrombosis. This study aims to demonstrate the feasibility and safety of low-dose prasugrel monotherapy following percutaneous coronary intervention (PCI) in Japanese patients presenting with chronic coronary syndromes (CCS) or non-ST-elevation acute coronary syndromes (NSTE-ACS). Four hundred patients with a SYNTAX score <23 requiring PCI due to CCS or NSTE-ACS will be screened and considered eligible for the study. The enrolment is planned in two phases: 1) 200 patients presenting with CCS, followed by 2) 200 patients presenting with NSTE-ACS. After optimal PCI with implantation of a SYNERGY (Boston Scientific) stent, patients will be enrolled and loaded with prasugrel 20 mg, followed by a maintenance dose of prasugrel 3.75 mg once daily without aspirin continued for 3 months in Phase 1 (CCS patients), and for 12 months in Phase 2 (NSTE-ACS patients). After these follow-up periods, prasugrel will be replaced by standard antiplatelet therapy according to local practice. The primary endpoint is a composite of cardiac death, target vessel myocardial infarction, or definite stent thrombosis after the index procedure. The primary bleeding endpoint is any Bleeding Academic Research Consortium type 3 or 5 bleeding occurring within 3 months of the index PCI for CCS patients, or 12 months for NSTE-ACS patients. The ASET Japan study is designed to demonstrate the feasibility and safety of reduced-dose prasugrel monotherapy after PCI in East Asian patients with acute and chronic coronary syndromes.
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Affiliation(s)
- Shinichiro Masuda
- Department of Cardiology, National University of Ireland Galway (NUIG), Galway, Ireland
| | - Takashi Muramatsu
- Department of Cardiology, Fujita Health University Hospital, Toyoake, Japan
| | - Yuki Ishibashi
- Division of Cardiology, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan
| | - Ken Kozuma
- Department of Cardiology, Teikyo University Hospital, Tokyo, Japan
| | - Kengo Tanabe
- Division of Cardiology, Mitsui Memorial Hospital, Tokyo, Japan
| | - Shimpei Nakatani
- Department of Cardiology, JCHO Hoshigaoka Medical Center, Osaka, Japan
| | - Norihiro Kogame
- Division of Cardiovascular Medicine, Toho University Ohashi Medical Center, Tokyo, Japan
| | - Masato Nakamura
- Division of Cardiovascular Medicine, Toho University Ohashi Medical Center, Tokyo, Japan
| | - Taku Asano
- Department of Cardiology, St. Luke's International Hospital, Tokyo, Japan
| | - Takayuki Okamura
- Division of Cardiology, Department of Clinical Science and Medicine, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Yosuke Miyazaki
- Division of Cardiology, Department of Clinical Science and Medicine, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Hiroki Tateishi
- Division of Cardiology, Department of Clinical Science and Medicine, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
- Department of Cardiology, Shibata Hospital, Aichi, Japan
| | - Yukio Ozaki
- Department of Cardiology, Fujita Health University Okazaki Medical Center, Aichi, Japan
| | - Gaku Nakazawa
- Department of Cardiology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Yoshihiro Morino
- Department of Cardiology, Iwate Medical University Hospital, Iwate, Japan
| | - Yuki Katagiri
- Department of Cardiology, Sapporo Higashi Tokushukai Hospital, Hokkaido, Japan
| | - Scot Garg
- Department of Cardiology, Royal Blackburn Hospital, Blackburn, UK
| | - Hironori Hara
- Department of Cardiology, National University of Ireland Galway (NUIG), Galway, Ireland
| | - Masafumi Ono
- Department of Cardiology, National University of Ireland Galway (NUIG), Galway, Ireland
| | - Hideyuki Kawashima
- Department of Cardiology, National University of Ireland Galway (NUIG), Galway, Ireland
- Department of Cardiology, Teikyo University Hospital, Tokyo, Japan
| | - Pedro A Lemos
- Heart Institute (InCor), University of São Paulo, São Paulo, Brazil
- Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - Patrick W Serruys
- Department of Cardiology, National University of Ireland Galway (NUIG), Galway, Ireland
| | - Yoshinobu Onuma
- Department of Cardiology, National University of Ireland Galway (NUIG), Galway, Ireland
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Kinoshita Y, Kato M, Sugizaki K, Ikeuchi S. Rabeprazole Coadministration Controls Ulcer Recurrence in Patients on Low-dose Aspirin Therapy: A Multicenter Prospective Study. Intern Med 2023; 62:495-502. [PMID: 35908971 PMCID: PMC10017235 DOI: 10.2169/internalmedicine.9646-22] [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] [Indexed: 11/09/2022] Open
Abstract
Objective To evaluate the efficacy and safety of rabeprazole coadministration with low-dose aspirin (LDA). Methods From 2015 to 2018, we conducted a large-scale, multicenter, prospective observational study to assess the safety and efficacy of treatment with rabeprazole (5 or 10 mg/day) in combination with LDA. Results The incidence of adverse reactions was 0.73% (11/1,513 patients), with no serious adverse reactions. We found no trend toward increases in the incidence of adverse reactions with increases in treatment duration. The cumulative recurrence rate of ulcers by Week 52 (Kaplan-Meier estimates) was 3.50% (range, 1.56-7.75%). No gastrointestinal bleeding was reported. Conclusion Rabeprazole in combination with LDA appears as safe and effective in real-world situations as in clinical trials.
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Affiliation(s)
| | - Mototsugu Kato
- National Hospital Organization, Hakodate National Hospital, Japan
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Abstract
A 77-year-old man presented with abdominal pain for 1 week. He was taking enteric-coated low-dose aspirin (LDA) to prevent secondary cardiovascular events and a proton pump inhibitor (PPI). Computed tomography indicated a small intestinal perforation; thus, small intestine resection was performed. Two months after surgery, he experienced a recurrence of the perforation. Since his repeated perforation was suspected to be due to LDA, LDA was discontinued. He has experienced no further recurrence since then. This is the first case of small intestinal perforation caused by enteric-coated LDA. Enteric-coated LDA may cause small intestinal perforation in patients with severe atherosclerosis under PPI administration.
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Affiliation(s)
| | - Ken-Ei Sada
- Department of Clinical Epidemiology, Kochi Medical School, Kochi University, Japan
| | - Haruo Sawada
- Department of Internal Medicine, Oida Hospital, Japan
| | - Jiro Oida
- Department of Surgery, Oida Hospital, Japan
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Quach DT, Mai BH, Tran MK, Dao LV, Tran HV, Vu KT, Vu KV, Pham HTT, Bui HH, Ho DDQ, Trinh DT, Nguyen VT, Duong TH, Tran TTK, Nguyen HTV, Nguyen TT, Nguyen TD, Nguyen LC, Dao HV, Thai KD, Phan NT, Le LT, Vo CHM, Ho PT, Nguyen TL, Le QD, Le NV, Phan HQ, Nguyen BC, Tran TT, Tran TV, Ta L. Vietnam Association of Gastroenterology (VNAGE) consensus on the management of Helicobacter pylori infection. Front Med (Lausanne) 2023; 9:1065045. [PMID: 36714104 PMCID: PMC9878302 DOI: 10.3389/fmed.2022.1065045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Accepted: 12/21/2022] [Indexed: 01/15/2023] Open
Abstract
Helicobacter pylori (H. pylori) infection is prevalent and has a rapidly increasing antibiotic resistance rate in Vietnam. Reinfection is quite common, and gastric carcinoma remains one of the most common malignancies, which is not uncommon to develop after successful eradication. The purpose of this consensus is to provide updated recommendations on the management of H. pylori infection in the country. The consensus panel consisted of 32 experts from 14 major universities and institutions in Vietnam who were invited to review the evidence and develop the statements using the Delphi method. The process followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The consensus level was defined as ≥80% for agreement on the proposed statements. Due to the limited availability of high-quality local evidence, this consensus was also based on high-quality evidence from international studies, especially those conducted in other populations in the Asia-Pacific region. The panel finally reached a consensus on 27 statements after two voting rounds, which consisted of four sections (1) indications for testing and selection of diagnostic tests (2), treatment regimens, (3) post-treatment confirmation of H. pylori status, and (4) reinfection prevention methods and follow-up after eradication. Important issues that require further evidence include studies on third-line regimens, strategies to prevent H. pylori reinfection, and post-eradication follow-up for precancerous gastric lesions. We hope this consensus will help guide the current clinical practice in Vietnam and promote multicenter studies in the country and international collaborations.
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Affiliation(s)
- Duc Trong Quach
- Department of Internal Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
- Nhan Dan Gia Dinh Hospital, Ho Chi Minh City, Vietnam
| | | | - Mien Kieu Tran
- Department of Internal Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Long Van Dao
- Internal Medicine Faculty, Hanoi Medical University, Hanoi, Vietnam
| | - Huy Van Tran
- Hue University of Medicine and Pharmacy, Hue, Vietnam
| | | | | | - Ho Thi-Thu Pham
- Internal Medicine Faculty, Hanoi Medical University, Hanoi, Vietnam
| | - Hoang Huu Bui
- Department of Internal Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | | | | | - Vinh Thuy Nguyen
- Department of Internal Medicine, Hanoi National University, Hanoi, Vietnam
| | - Thai Hong Duong
- Department of Internal Medicine, Thai Nguyen University of Medicine and Pharmacy, Thai Nguyen, Vietnam
| | - Tuong Thi-Khanh Tran
- Department of Internal Medicine, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam
| | | | | | | | | | - Hang Viet Dao
- Internal Medicine Faculty, Hanoi Medical University, Hanoi, Vietnam
| | | | | | | | | | | | | | - Quang Dinh Le
- Department of Internal Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Nho Viet Le
- Department of Internal Medicine, Da Nang University of Medical Technology and Pharmacy, Da Nang, Vietnam
| | | | | | - Trung Thien Tran
- Department of Internal Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | | | - Long Ta
- 108 Military Central Hospital, Hanoi, Vietnam
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10
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Hawkey C, Avery A, Coupland CAC, Crooks C, Dumbleton J, Hobbs FDR, Kendrick D, Moore M, Morris C, Rubin G, Smith M, Stevenson D. Helicobacter pylori eradication for primary prevention of peptic ulcer bleeding in older patients prescribed aspirin in primary care (HEAT): a randomised, double-blind, placebo-controlled trial. Lancet 2022; 400:1597-1606. [PMID: 36335970 DOI: 10.1016/s0140-6736(22)01843-8] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Revised: 09/13/2022] [Accepted: 09/20/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND Peptic ulcers in patients receiving aspirin are associated with Helicobacter pylori infection. We aimed to investigate whether H pylori eradication would protect against aspirin-associated ulcer bleeding. METHODS We conducted a randomised, double-blind, placebo-controlled trial (Helicobacter Eradication Aspirin Trial [HEAT]) at 1208 primary care centres in the UK, using routinely collected clinical data. Eligible patients were aged 60 years or older who were receiving aspirin at a daily dose of 325 mg or less (with four or more 28-day prescriptions in the past year) and had a positive C13 urea breath test for H pylori at screening. Patients receiving ulcerogenic or gastroprotective medication were excluded. Participants were randomly assigned (1:1) to receive either a combination of oral clarithromycin 500 mg, metronidazole 400 mg, and lansoprazole 30 mg (active eradication), or oral placebo (control), twice daily for 1 week. Participants, their general practitioners and health-care providers, and the research nurses, trial team, adjudication committee, and analysis team were all masked to group allocation throughout the trial. Follow-up was by scrutiny of electronic data in primary and secondary care. The primary outcome was time to hospitalisation or death due to definite or probable peptic ulcer bleeding, and was analysed by Cox proportional hazards methods in the intention-to-treat population. This trial is registered with EudraCT, 2011-003425-96. FINDINGS Between Sept 14, 2012, and Nov 22, 2017, 30 166 patients had breath testing for H pylori, 5367 had a positive result, and 5352 were randomly assigned to receive active eradication (n=2677) or placebo (n=2675) and were followed up for a median of 5·0 years (IQR 3·9-6·4). Analysis of the primary outcome showed a significant departure from proportional hazards assumptions (p=0·0068), requiring analysis over separate time periods. There was a significant reduction in incidence of the primary outcome in the active eradication group in the first 2·5 years of follow-up compared with the control group (six episodes adjudicated as definite or probable peptic ulcer bleeds, rate 0·92 [95% CI 0·41-2·04] per 1000 person-years vs 17 episodes, rate 2·61 [1·62-4·19] per 1000 person-years; hazard ratio [HR] 0·35 [95% CI 0·14-0·89]; p=0·028). This advantage remained significant after adjusting for the competing risk of death (p=0·028) but was lost with longer follow-up (HR 1·31 [95% CI 0·55-3·11] in the period after the first 2·5 years; p=0·54). Reports of adverse events were actively solicited; taste disturbance was the most common event (787 patients). INTERPRETATION H pylori eradication protects against aspirin-associated peptic ulcer bleeding, but this might not be sustained in the long term. FUNDING National Institute for Health and Care Research Health Technology Assessment.
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Affiliation(s)
- Chris Hawkey
- STAR (Simple Trials for Academic Research) Unit, School of Medicine, University of Nottingham, Nottingham, UK.
| | - Anthony Avery
- Centre for Academic Primary Care, School of Medicine, University of Nottingham, Nottingham, UK
| | - Carol A C Coupland
- Centre for Academic Primary Care, School of Medicine, University of Nottingham, Nottingham, UK
| | - Colin Crooks
- STAR (Simple Trials for Academic Research) Unit, School of Medicine, University of Nottingham, Nottingham, UK
| | - Jennifer Dumbleton
- STAR (Simple Trials for Academic Research) Unit, School of Medicine, University of Nottingham, Nottingham, UK
| | - F D Richard Hobbs
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Denise Kendrick
- Centre for Academic Primary Care, School of Medicine, University of Nottingham, Nottingham, UK
| | - Michael Moore
- Primary Care Research Centre, University of Southampton, Southampton, UK
| | | | - Gregory Rubin
- Population Health Sciences Institute, Newcastle University, Newcastle, UK
| | - Murray Smith
- Community and Health Research Unit, University of Lincoln, Lincoln, UK
| | - Diane Stevenson
- STAR (Simple Trials for Academic Research) Unit, School of Medicine, University of Nottingham, Nottingham, UK
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11
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Prevalence of H. pylori among patients undergoing coronary angiography (The HP-DAPT prevalence study). Sci Rep 2022; 12:16591. [PMID: 36198683 PMCID: PMC9535026 DOI: 10.1038/s41598-022-17034-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Accepted: 07/19/2022] [Indexed: 11/16/2022] Open
Abstract
Helicobacter pylori (H. pylori) screening and treatment is recommended for patients on chronic aspirin (ASA) therapy to reduce the risk of gastrointestinal bleeding. Coronary artery disease patients requiring combination antithrombotic therapy (dual antiplatelet therapy; DAPT, or dual pathway inhibition; DPI) are at an even higher risk of GI bleeding. Therefore, we aimed to evaluate the prevalence of H. pylori among patients referred for angiography and likely to receive DAPT or DPI. This single-center prospective observational study recruited patients undergoing coronary angiography and with the possibility of requiring DAPT or DPI. All included patients underwent H. pylori serology testing. Multivariable logistic regression was performed to determine predictors of seropositivity. 195 patients were included in the analysis. Mean age was 67 years, 50% had known prior CAD, and 49% underwent coronary intervention. H. pylori serology was positive in 36%. Chronic kidney disease (odds ratio [OR] 2.76; 95% confidence interval [CI] 1.24 to 6.15; p = 0.01) and chronic obstructive pulmonary disease (OR 2.52; 95% CI 1.14 to 5.55; p = 0.02) history were independent predictors of H. pylori seropositivity. Given the clinically significant prevalence of H. pylori seropositivity among patients referred for angiography, systematic screening strategies and eradication of H. pylori could significantly reduce the incidence of GI bleeding in patients requiring DAPT or DPI.
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12
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Chen X, Gao F, Zhang J. Lactobacillus complex capsules ameliorate aspirin-related small intestinal mucosal injury: a prospective, randomized, controlled clinical trial. Scand J Gastroenterol 2022; 57:1195-1201. [PMID: 35534443 DOI: 10.1080/00365521.2022.2073184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Aspirin can reduce cardiovascular disease risk; however, it can increase the risk of gastrointestinal injury. Lactobacilli have some protective effects; however, there are few studies on their effects on humans. This study investigates the effects of Lactobacillus complex capsule treatment on the aspirin-related small intestinal mucosal injury. METHODS This single-center, prospective, randomized controlled clinical trial included 69 patients using enteric-coated aspirin for >1 month between May and December 2019. After baseline magnetically controlled capsule endoscopy (MCCE), patients with aspirin-related small intestinal mucosal injury were randomly assigned (1:1) to receive enteric-coated aspirin and Lactobacillus complex capsules containing a combination of Lactobacillus rhamnosus I, Lactobacillus rhamnosus II, and Enterococcus faecium (probiotics group) or enteric-coated aspirin only (control group) for 2 months. After treatment, the patient underwent MCCE again. The primary outcome was the change in small intestinal mucosal injury scores from baseline to post-intervention. RESULTS Twenty-five patients in the probiotics group and 28 in the control group completed the trial. The decrease in small intestinal mucosal injury scores from baseline to post-intervention was significantly greater in the probiotics group than that in the control group (p < .001). The improvement rates of red spots and erosions in the probiotics group were higher compared with the control group (p = .027 and .022, respectively), and the improvement rate of small intestinal ulcers in the probiotics group was 75.0%; however, there was no improvement in the control group. CONCLUSION Lactobacillus complex capsules can ameliorate aspirin-related small intestinal mucosal injury.
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Affiliation(s)
- Xue Chen
- Department of Gastroenterology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Feng Gao
- Department of Gastroenterology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Jie Zhang
- Department of Gastroenterology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
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13
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Nguyen TNM, Sha S, Chen LJ, Holleczek B, Brenner H, Schöttker B. Strongly increased risk of gastric and duodenal ulcers among new users of low-dose aspirin: results from two large cohorts with new-user design. Aliment Pharmacol Ther 2022; 56:251-262. [PMID: 35621052 DOI: 10.1111/apt.17050] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 03/31/2022] [Accepted: 05/13/2022] [Indexed: 01/01/2023]
Abstract
BACKGROUND Low-dose aspirin is a risk factor for peptic ulcer disease but previous, population-based cohort studies may have underestimated the low-dose aspirin risk because they did not use a new-user design. Gastrointestinal bleeding occurs more frequently early after initiation of low-dose aspirin therapy than in later years. AIM To assess the associations of low-dose aspirin with gastric and duodenal ulcer incidence in prevalent- and new-user design. METHODS Multivariate Cox regression models in the German ESTHER study (N = 7737) and the UK Biobank (N = 213,598) with more than 10 years of follow-up. RESULTS In the prevalent-user design, there was no significant association between low-dose aspirin and gastric ulcer observed in both cohorts. Furthermore, low-dose aspirin was weakly, statistically significantly associated with prevalent duodenal ulcer in the UK Biobank (hazard ratio [95% confidence interval]: 1.27 [1.07-1.51]) but not in the ESTHER study (1.33 [0.54-3.29]). When restricting the exposure to only new users, the hazard ratios for incident gastric and duodenal ulcer disease were 1.82 [1.58-2.11] and 1.66 [1.36-2.04] in the UK Biobank, respectively, and 2.83 [1.40-5.71] and 3.89 [1.46-10.42] in the ESTHER study, respectively. CONCLUSIONS This study shows that low-dose aspirin is an independent risk factor for both gastric and duodenal ulcers. The associations were not significant or weak in the prevalent-user design and strong and statistically significant in the new-user design in both cohorts. Thus, it is important to weigh risks against benefits when low-dose aspirin treatment shall be initiated and to monitor adverse gastrointestinal symptoms after the start of low-dose aspirin therapy.
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Affiliation(s)
- Thi Ngoc Mai Nguyen
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Network Aging Research, University of Heidelberg, Heidelberg, Germany
| | - Sha Sha
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Li-Ju Chen
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | | | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Network Aging Research, University of Heidelberg, Heidelberg, Germany
| | - Ben Schöttker
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Network Aging Research, University of Heidelberg, Heidelberg, Germany
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14
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Randomized controlled trial of early endoscopy for upper gastrointestinal bleeding in acute coronary syndrome patients. Sci Rep 2022; 12:5798. [PMID: 35388113 PMCID: PMC8986851 DOI: 10.1038/s41598-022-09911-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Accepted: 03/30/2022] [Indexed: 12/14/2022] Open
Abstract
Acute upper gastrointestinal bleeding (UGIB) in acute coronary syndrome (ACS) patients are not uncommon, particularly under dual antiplatelet therapy (DAPT). The efficiency and safety of early endoscopy (EE) for UGIB in these patients needs to be elucidated. This multicenter randomized controlled trial randomized recent ACS patients presenting acute UGIB to non-EE and EE groups. All eligible patients received intravenous proton pump inhibitor therapy. Those in EE group underwent therapeutic endoscopy within 24 h after bleeding. The data regarding efficacy and safety of EE were analyzed. It was early terminated because the UGIB rate was lower than expected and interim analysis was done. In total, 43 patients were randomized to non-EE (21 patients) and EE (22 patients) groups. The failure rate of control hemorrhage (intention-to-treat [ITT] 4.55% vs. 23.81%, p < 0.001; per-protocol [PP] 0% vs. 4.55%, p = 0.058) and 3-day rebleeding rate (ITT 4.55% vs. 28.57%, p = 0.033; PP 0% vs. 21.05%, p = 0.027) were lower in EE than non-EE group. The mortality, minor and major complication rates were not different between two groups. Male patients were at higher risk of minor and major complications after EE with OR (95% CI) of 3.50 (1.15–10.63) and 4.25 (1.43–12.63), respectively. In multivariate analysis, EE was associated with lower needs for blood transfusion (HR 0.13, 95% CI 0.02–0.98). Among patients who discontinued DAPT during acute UGIB, a higher risk (OR 5.25, 95% CI 1.21–22.74) of coronary artery stent re-thrombosis within 6 months was noticed. EE for acute UGIB in recent ACS patients has higher rate of bleeding control, lower 3-day rebleeding rate and lower needs for blood transfusion, but more complications in male patients. Further enrollment is mandatory to avoid bias from small sample size (ClinicalTrial.gov Number NCT02618980, registration date 02/12/2015).
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15
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Angiolillo DJ, Prats J, Deliargyris EN, Schneider DJ, Scheiman J, Kimmelstiel C, Steg PG, Alberts M, Rosengart T, Mehran R, Bhatt DL. Pharmacokinetic and Pharmacodynamic Profile of a Novel Phospholipid Aspirin Formulation. Clin Pharmacokinet 2022; 61:465-479. [PMID: 35060092 PMCID: PMC8773391 DOI: 10.1007/s40262-021-01090-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/01/2021] [Indexed: 12/25/2022]
Abstract
Aspirin is one of the most widely used medicines. Although aspirin is commonly utilized for the treatment of several medical conditions, its broadest uptake is for the prevention of recurrent ischemic events in patients with atherosclerotic disease. Its mechanism of action of inhibiting platelet activation via blockade of thromboxane A2 production is unique and is not covered by any other antiplatelet agents. While plain, uncoated, immediate-release aspirin is used in acute settings to help assure rapid absorption, enteric-coated aspirin formulations dominate current chronic use, particularly in North America, including for secondary prevention of cardiovascular events. The unmet needs with current aspirin formulations include a high risk of gastrointestinal (GI) adverse events with plain aspirin, which enteric-coated formulations are not able to overcome, and subject to erratic absorption leading to reduced drug bioavailability. These observations underscore the need for aspirin formulations with a more favorable safety and efficacy profile. Phospholipid-aspirin complex (PL-ASA) is a novel formulation designed to address these needs. It is associated with reduced local acute GI injury compared with plain aspirin, and predictable absorption resulting in more reliable platelet inhibition compared with enteric-coated tablets. This review explores the rationale and pharmacologic profile of PL-ASA intended to address the unmet needs for aspirin therapy.
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Affiliation(s)
- Dominick J Angiolillo
- Division of Cardiology, University of Florida College of Medicine, 655 West 8th street, Jacksonville, FL, 32209, USA.
| | | | | | - David J Schneider
- Cardiovascular Division Department of Medicine and Cardiovascular Research Institute, University of Vermont Burlington, Burlington, VT, USA
| | - James Scheiman
- iDivision of Gastroenterology and Hepatology, University of Virginia, Charlottesville, VA, USA
| | - Carey Kimmelstiel
- Division of Cardiology, Tufts Medical Center Boston, Boston, MA, USA
| | - Ph Gabriel Steg
- Université de Paris, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, INSERM-U1148, Paris, France
| | - Mark Alberts
- Department of Neurology, Hartford Hospital, Hartford, CT, USA
| | - Todd Rosengart
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA
| | - Roxana Mehran
- Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Deepak L Bhatt
- Brigham and Women's Hospital Heart and Vascular Center, Harvard Medical School, Boston, MA, USA
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16
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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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17
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Salari N, Darvishi N, Shohaimi S, Bartina Y, Ahmadipanah M, Salari HR, Mohammadi M. The Global Prevalence of Peptic Ulcer in the World: a Systematic Review and Meta-analysis. Indian J Surg 2021. [DOI: 10.1007/s12262-021-03189-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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18
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Hofer SJ, Davinelli S, Bergmann M, Scapagnini G, Madeo F. Caloric Restriction Mimetics in Nutrition and Clinical Trials. Front Nutr 2021; 8:717343. [PMID: 34552954 PMCID: PMC8450594 DOI: 10.3389/fnut.2021.717343] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Accepted: 08/13/2021] [Indexed: 12/29/2022] Open
Abstract
The human diet and dietary patterns are closely linked to the health status. High-calorie Western-style diets have increasingly come under scrutiny as their caloric load and composition contribute to the development of non-communicable diseases, such as diabetes, cancer, obesity, and cardiovascular disorders. On the other hand, calorie-reduced and health-promoting diets have shown promising results in maintaining health and reducing disease burden throughout aging. More recently, pharmacological Caloric Restriction Mimetics (CRMs) have gained interest of the public and scientific community as promising candidates that mimic some of the myriad of effects induced by caloric restriction. Importantly, many of the CRM candidates activate autophagy, prolong life- and healthspan in model organisms and ameliorate diverse disease symptoms without the need to cut calories. Among others, glycolytic inhibitors (e.g., D-allulose, D-glucosamine), hydroxycitric acid, NAD+ precursors, polyamines (e.g., spermidine), polyphenols (e.g., resveratrol, dimethoxychalcones, curcumin, EGCG, quercetin) and salicylic acid qualify as CRM candidates, which are naturally available via foods and beverages. However, it is yet unclear how these bioactive substances contribute to the benefits of healthy diets. In this review, we thus discuss dietary sources, availability and intake levels of dietary CRMs. Finally, since translational research on CRMs has entered the clinical stage, we provide a summary of their effects in clinical trials.
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Affiliation(s)
- Sebastian J. Hofer
- Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria
- BioTechMed-Graz, Graz, Austria
- Field of Excellence BioHealth, University of Graz, Graz, Austria
| | - Sergio Davinelli
- Department of Medicine and Health Sciences “V. Tiberio”, University of Molise, Campobasso, Italy
| | - Martina Bergmann
- Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria
| | - Giovanni Scapagnini
- Department of Medicine and Health Sciences “V. Tiberio”, University of Molise, Campobasso, Italy
| | - Frank Madeo
- Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria
- BioTechMed-Graz, Graz, Austria
- Field of Excellence BioHealth, University of Graz, Graz, Austria
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19
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Sohn SH, Kim TS, Kim JW, Yoo SM, Jo WM. Anti-thrombotic and anti-inflammatory activity of sulodexide compared to aspirin in the rat model. Clin Hemorheol Microcirc 2021; 77:435-442. [PMID: 33386798 DOI: 10.3233/ch-201043] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Although the number of vascular surgeries performed is increasing, the incidence of complications associated with this surgery has not improved and re-operations are frequently required. Thrombosis in a vessel is the most hazardous postoperative complication. OBJECTIVE The aim of this study was to evaluate the anti-thrombotic and anti-inflammatory effects of sulodexide compared to aspirin in a rat model. METHODS We divided the animals into three groups (sham (saline), aspirin, and sulodexide). The abdominal aorta was surgically opened and closed, primarily with 8/0 Prolene sutures. Postoperatively, saline, aspirin, or sulodexide was administered by oral gavage for 14 days to the rats. The degree of neovascularization, thrombus, calcification, inflammatory infiltrates, and fibrosis were analyzed histopathologically by hematoxylin and eosin staining. RESULTS There was no significant difference in the incidence of postoperative thrombogenesis, but less calcification and inflammatory infiltrates were observed in the sulodexide group compared to the aspirin group. Histopathologic score revealed less infiltration of inflammatory cells and mild calcification for the sulodexide group (0.17±0.41 and 1.33±0.52, respectively) compared to the aspirin group (0.67±0.52 and 1.67±0.52, respectively) at days 14. CONCLUSIONS This study offers the possibility that sulodexide could be used as an aspirin substitute for the postoperative management of vascular patients, with low gastrointestinal discomfort. In addition, it may also offer reduced postoperative calcification and inflammation.
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Affiliation(s)
- Sung-Hwa Sohn
- Department of Thoracic & Cardiovascular Surgery, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Tae Sik Kim
- Department of Thoracic & Cardiovascular Surgery, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Ji-Won Kim
- Department of Thoracic & Cardiovascular Surgery, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Sung Mook Yoo
- Department of Thoracic & Cardiovascular Surgery, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Won-Min Jo
- Department of Thoracic & Cardiovascular Surgery, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
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20
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Zhao C, Wang J, Xiao Q. Efficacy of Teprenone for Prevention of NSAID-Induced Gastrointestinal Injury: A Systematic Review and Meta-Analysis. Front Med (Lausanne) 2021; 8:647494. [PMID: 33898483 PMCID: PMC8058206 DOI: 10.3389/fmed.2021.647494] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 03/12/2021] [Indexed: 12/23/2022] Open
Abstract
Background: The study aimed to conduct a systematic review and meta-analysis comparing the efficacy of teprenone with control or other drugs for reducing the incidence of gastrointestinal (GI) adverse events in patients receiving long-term non-steroidal anti-inflammatory drugs (NSAIDs). Methods: Databases of PubMed, Embase, BioMed Central, CENTRAL, and Google Scholar were searched up to November 10th, 2020 for randomized controlled trials (RCTs) comparing teprenone with control or other drugs. A random-effects model was used for the meta-analysis. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was used for assessing the certainty of evidence. Results: Seven RCTs were included. Six compared teprenone with control and one with famotidine. Meta-analysis indicated a statistically significant reduced risk of GI ulcers in patients receiving teprenone as compared to control after 12 weeks/3months (RR 0.37 95% CI 0.17, 0.18 I 2 = 0% p = 0.01). Pooled data of three open-label studies indicated statistically significant reduction of GI symptoms in patients on teprenone as compared to control at 6 months and 12 months, but not at 3 months. Comparing teprenone with control, our analysis indicated non-significant but a tendency of better reduction in Modified Lanza Score (MLS) with teprenone. The RCT comparing teprenone to famotidine demonstrated better reduction of MLS with famotidine. The certainty of evidence-based on GRADE was deemed to be low. Conclusion: Low-quality evidence indicates a beneficial role of teprenone in preventing GI injuries in patients receiving long-term NSAIDs. Further high-quality RCTs comparing teprenone with placebo as well as other gastroprotective drugs are needed to strengthen current evidence.
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Affiliation(s)
- Chongxiang Zhao
- Department of Gastroenterology, Zaozhuang Hospital of Traditional Chinese Medicine, Zaozhuang, China
| | - Jingwu Wang
- Department of Gastroenterology, Zaozhuang Hospital of Traditional Chinese Medicine, Zaozhuang, China
| | - Qiang Xiao
- Department of Gastroenterology, Zaozhuang Hospital of Traditional Chinese Medicine, Zaozhuang, China
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21
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Kakiuchi T, Kumamoto T, Koji A, Matsuo M. Low-dose aspirin-induced gastric mucosal injury after Fontan surgery in an adolescent. Clin Case Rep 2021; 9:2460-2464. [PMID: 33936713 PMCID: PMC8077239 DOI: 10.1002/ccr3.4070] [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: 02/02/2021] [Revised: 03/08/2021] [Accepted: 03/08/2021] [Indexed: 11/10/2022] Open
Abstract
Low-dose aspirin (LDA)-induced gastric mucosal injury always requires rigorous follow-up while taking LDA, even in adolescents, and after a long time from the start of LDA.
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Affiliation(s)
| | - Takashi Kumamoto
- Department of PediatricsFaculty of MedicineSaga UniversitySagaJapan
| | - Azusa Koji
- Department of PediatricsFaculty of MedicineSaga UniversitySagaJapan
| | - Muneaki Matsuo
- Department of PediatricsFaculty of MedicineSaga UniversitySagaJapan
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22
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Weltermann T, Schulz C, Macke L. Effect of frequently prescribed drugs on gastric cancer risk. Best Pract Res Clin Gastroenterol 2021; 50-51:101741. [PMID: 33975680 DOI: 10.1016/j.bpg.2021.101741] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 03/09/2021] [Accepted: 03/10/2021] [Indexed: 02/07/2023]
Abstract
Gastric cancer is the fifth leading cancer worldwide. Infection with Helicobacter pylori represents the major risk factor, but only a small fraction of infected individuals will develop neoplasia. The progression of advanced gastric lesions to cancer is influenced by characteristics of the bacterial strain, host genetic and environmental factors. Recently, the effect of medications on gastric cancer risk has gained interest, because many commonly prescribed drugs affect gastric homeostasis. While non-steroidal anti-inflammatory drugs (NSAIDs) are a frequent cause of gastric ulcer disease, low-dose aspirin has been propagated for chemoprevention of various tumour entities. Beneficial effects of cyclooxygenase-inhibition for gastric cancer prevention is plausible, but its clinical relevance remains unclear. Furthermore, anti-tumorous effects have been postulated for statins and metformin. On the contrary, proton pump inhibitors (PPIs), which are commonly used for prevention of gastric ulcers and bleeding, have been associated with an increased gastric cancer risk in large observational studies. Most of these observations still require confirmation in prospective controlled trials. NSAIDs, statins and metformin have also been investigated as concomitant cancer treatment, but studies did not show convincing results to date. Here, we review the available evidence and possible mechanisms for the role of PPIs, NSAIDs, statins and metformin in gastric carcinogenesis, and discuss possible implications for clinical practice.
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Affiliation(s)
- Theresa Weltermann
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany, Marchioninistr. 15, 81377, Munich, Germany.
| | - Christian Schulz
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany, Marchioninistr. 15, 81377, Munich, Germany.
| | - Lukas Macke
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany, Marchioninistr. 15, 81377, Munich, Germany.
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Orally Administered NSAIDs-General Characteristics and Usage in the Treatment of Temporomandibular Joint Osteoarthritis-A Narrative Review. Pharmaceuticals (Basel) 2021; 14:ph14030219. [PMID: 33807930 PMCID: PMC7998670 DOI: 10.3390/ph14030219] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Revised: 03/02/2021] [Accepted: 03/03/2021] [Indexed: 02/07/2023] Open
Abstract
Background: Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative joint disease. The aim of this review was to present the general characteristics of orally administered nonsteroidal anti-inflammatory drugs (NSAIDs) and to present the efficacy of NSAIDs in the treatment of TMJ OA. Methods: PubMed database was analyzed with the keywords: "(temporomandibular joint) AND ((disorders) OR (osteoarthritis) AND (treatment)) AND (nonsteroidal anti-inflammatory drug)". After screening of 180 results, 6 studies have been included in this narrative review. Results and Conclusions: Nonsteroidal anti-inflammatory drugs are one of the most commonly used drugs for alleviation of pain localized in the orofacial area. The majority of articles predominantly examined and described diclofenac sodium in the treatment of pain in the course of TMJ OA. Because of the limited number of randomized studies evaluating the efficacy of NSAIDs in the treatment of TMJ OA, as well as high heterogeneity of published researches, it seems impossible to draw up unequivocal recommendations for the usage of NSAIDs in the treatment of TMJ OA. However, it is highly recommended to use the lowest effective dose of NSAIDs for the shortest possible time. Moreover, in patients with increased risk of gastrointestinal complications, supplementary gastroprotective agents should be prescribed.
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Aspirin in Primary Prevention: What Changed? A Critical Appraisal of Current Evidence. Am J Cardiol 2021; 141:38-48. [PMID: 33221264 DOI: 10.1016/j.amjcard.2020.11.014] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 11/05/2020] [Accepted: 11/06/2020] [Indexed: 12/12/2022]
Abstract
Aspirin has been the mainstay of both secondary and primary prevention of cardiovascular disease for half a century. In 2018, 3 trials showed a modest reduction in cardiovascular outcomes that appeared counterbalanced by the risk of clinically significant bleeding. The latest ACC/AHA primary prevention guidelines downgraded their recommendation for aspirin use in primary prevention to that of physician preference. Despite the consistent and robust evidence previously supporting the use of aspirin in cardiovascular disease prevention, little discussion has been given to mechanisms or analytic explanations for this revision of recommendations. In this review, we explore 3 possible mechanisms that may have contributed to the alteration of our perception of aspirin's role in primary prevention. These include changes in the population potentially using aspirin in primary prevention, changes in cardiovascular disease and its presentation, and changes in aspirin itself. Here we present a translational look at knowledge gaps that should be addressed to better guide contemporary aspirin use in primary prevention. In conclusion, based on these considerations, the current recommendations might be improved by recalibration of the cardiovascular risk threshold above which aspirin should be recommended for primary prevention, including the incorporation of newer risk assessment modalities such as calcium scoring. A second enhancement would be developing a bleeding risk calculator to support clinicians' assessment of risk vs benefit. The use of enteric-coated aspirin vs noncoated aspirin should also be reassessed.
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25
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Tseng ZF, Hsu PI, Peng NJ, Kao SS, Tsay FW, Cheng JS, Chen WC, Tsai KF, Tang SY, Chuah SK, Shie CB. Omeprazole vs famotidine for the prevention of gastroduodenal injury in high-risk users of low-dose aspirin: A randomized controlled trial. J Chin Med Assoc 2021; 84:19-24. [PMID: 33230059 DOI: 10.1097/jcma.0000000000000465] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Low-dose aspirin is widely used in the prevention of cardiovascular diseases. However, the use of aspirin is associated with an increased risk of gastrointestinal injury. METHODS Low-dose aspirin users with a history of peptic ulcers who did not have gastroduodenal mucosal breaks at initial endoscopy were randomly assigned to receive famotidine (20 mg bid) or omeprazole (20 mg qd) for 6 months. Follow-up endoscopy was performed at the end of the sixth month and whenever epigastric discomfort, hematemesis, or melena occurred. The primary end point was the occurrence of gastroduodenal mucosal breaks. The secondary end points were (1) the occurrence of gastroduodenal ulcers and (2) the occurrence of gastroduodenal bleeding. RESULT Between November 2013 and June 2018, 170 patients were randomly assigned to receive either famotidine (n = 84) or omeprazole (n = 86). The incidence of gastroduodenal mucosal breaks was 33.8% among the patients receiving famotidine, and 19.8% among those receiving omeprazole (95% CI: 0.4%-27.5%; p = 0.045). The two patient groups had comparable incidence rates of gastroduodenal ulcers (20.0% vs 9.8%; p = 0.071), and gastroduodenal bleeding (2.5% vs 0%; p = 0.243). Multivariate analysis showed that use of the proton pump inhibitor was an independent protective factor (odds ratio: 0.47; 95% CI: 0.23-0.99; p = 0.047), and that smoking was a risk factor for mucosal breaks (odds ratio: 3.84; 95% CI: 1.52-9.71; p = 0.004). CONCLUSION Proton pump inhibitor was superior to histamine-2 receptor antagonist in the prevention of gastroduodenal mucosal breaks in high-risk users of low-dose aspirin, and smoking was an independent risk factor for developing gastroduodenal mucosal breaks.
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Affiliation(s)
- Zhi-Fu Tseng
- Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
| | - Ping-I Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, An Nan Hospital, China Medical University, Tainan, Taiwan, ROC
| | - Nan-Jing Peng
- Department of Nuclear Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan, ROC
| | - Sung-Shuo Kao
- Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
| | - Feng-Woei Tsay
- Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
| | - Jin-Shiung Cheng
- Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
| | - Wen-Chi Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
| | - Kun-Feng Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, An Nan Hospital, China Medical University, Tainan, Taiwan, ROC
| | - Sheng-Yeh Tang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, An Nan Hospital, China Medical University, Tainan, Taiwan, ROC
| | - Seng-Kee Chuah
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC
| | - Chang-Bih Shie
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, An Nan Hospital, China Medical University, Tainan, Taiwan, ROC
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27
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Joo MK. [ Helicobacter pylori Eradication in Drug-related Peptic Ulcer]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2020; 76:227-231. [PMID: 33234768 DOI: 10.4166/kjg.2020.141] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Revised: 10/23/2020] [Accepted: 10/23/2020] [Indexed: 06/11/2023]
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin are the most frequently prescribed drugs worldwide, and their long-term use often leads to peptic ulcers (PUs) along with serious complications, such as bleeding and perforation. Helicobacter pylori (H. pylori) infection is a significant risk factor for developing NSAID-related PU and ulcer bleeding during long-term aspirin use. In a revised version of the Clinical Guidelines for Drug-induced Peptic Ulcer, two statements regarding H. pylori eradication are recommended. 1) Patients scheduled for long-term NSAID therapy should be tested and treated for H. pylori infection to prevent PU and its complications. 2) Patients with a history of PU receiving long-term low-dose aspirin (LDA) therapy should undergo treatment for H. pylori infection to prevent PU and its complications. On the other hand, unlike NSAID-naïve patients, the preventive effects of H. pylori eradication in chronic NSAID users are unclear. In addition, anti-ulcer drugs, such as proton pump inhibitors, may be necessary for maintenance therapy after H. pylori eradication in a subset of long-term LDA users, particularly if the patients are taking concomitant antiplatelet agents or anticoagulants.
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Affiliation(s)
- Moon Kyung Joo
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
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28
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Li Z, Wang Z, Shen B, Chen C, Ding X, Song H. Effects of aspirin on the gastrointestinal tract: Pros vs. cons. Oncol Lett 2020; 20:2567-2578. [PMID: 32782574 PMCID: PMC7400979 DOI: 10.3892/ol.2020.11817] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Accepted: 05/28/2020] [Indexed: 02/07/2023] Open
Abstract
Acetylsalicylic acid, also known as aspirin, is often used in clinical antipyretic, analgesic and antiplatelet therapy. Aspirin can cause numerous side effects in the gastrointestinal (GI) tract, ranging from unpleasant GI symptoms without gastric mucosal lesions to ulcer bleeding and even death. However, recent studies have found that aspirin can significantly prevent GI tumors. Despite impressive advances in cancer research, screening and treatment options, GI tumors remain a leading cause of death worldwide. Prevention is a far better option than treatment for tumors. Therefore, the present review assesses the pros and cons of aspirin on the GI tract and, on this the basis, the appropriate dose of aspirin to protect it.
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Affiliation(s)
- Zhuoya Li
- Department of Internal Medicine, The Medical School of Ningbo University, Ningbo, Zhejiang 315000, P.R. China
- Department of Gastroenterology, Ningbo First Hospital, Ningbo, Zhejiang 315000, P.R. China
| | - Zheng Wang
- Department of Gastroenterology, Ningbo First Hospital, Ningbo, Zhejiang 315000, P.R. China
- Department of Internal Medicine, The Medical School of Zhejiang University, Hangzhou, Zhejiang 310000, P.R. China
| | - Baile Shen
- Department of Internal Medicine, The Medical School of Ningbo University, Ningbo, Zhejiang 315000, P.R. China
- Department of Gastroenterology, Ningbo First Hospital, Ningbo, Zhejiang 315000, P.R. China
| | - Chen Chen
- Department of Internal Medicine, The Medical School of Ningbo University, Ningbo, Zhejiang 315000, P.R. China
- Department of Gastroenterology, Ningbo First Hospital, Ningbo, Zhejiang 315000, P.R. China
| | - Xiaoyun Ding
- Department of Gastroenterology, Ningbo First Hospital, Ningbo, Zhejiang 315000, P.R. China
| | - Haojun Song
- Department of Gastroenterology, Ningbo First Hospital, Ningbo, Zhejiang 315000, P.R. China
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Iwamoto J, Murakami M, Monma T, Ueda H, Tamamushi M, Konishi N, Yara SI, Hirayama T, Ikegami T, Honda A, Mizokami Y. Current states of prevention of drug-induced gastroduodenal ulcer in real clinical practice: a cross-sectional study. J Clin Biochem Nutr 2020; 66:158-162. [PMID: 32231413 DOI: 10.3164/jcbn.19-66] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2019] [Accepted: 12/04/2019] [Indexed: 02/06/2023] Open
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin (LDA) are the most common causes of drug-induced gastroduodenal ulcer and We investigated preventive treatment with use of concomitant anti-ulcer drugs and the clinical features of gastroduodenal ulcer in cases treated with these drugs. Patients with gastroduodenal ulcer and patients with bleeding were classified into 3 groups: LDA, non-aspirin NSAIDs, and those taking neither aspirin nor NSAIDs. Chronological changes over the past 16 years (1st-5th period) were investigated. The status of prevention of ulcer and clinical features were examined. From January 2002 to December 2018, the ratio of all patients taking NSAIDs and LDA increased significantly until 3rd period (p<0.05), but then started to decrease in 4th period; and the percentage of all patients taking NSAIDs and LDA decreased significantly (p<0.05) until 5th period. Among the 292 patients with gastroduodenal ulcer and the 121 patients with a bleeding ulcer taking NSAIDs and LDA, 16 (5.5%) and 9 (7.4%), respectively, were receiving preventive treatment with concomitant anti-ulcer drugs. The percentages of patients taking LDA and other antiplatelet drugs in patients with bleeding gastroduodenal ulcer were significantly higher than those in patients with non-bleeding. In conclusion, although the percentages of patients with gastroduodenal ulcer taking NSAIDs or LDA have not recently increased in real-world practice, preventive treatment in these patients is still low. This low rate of prevention suggests the need to enlighten physicians about preventive treatment because drug withdrawal of LDA has a high risk of cardiovasculr and cerebrovascular events.
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Affiliation(s)
- Junichi Iwamoto
- Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Chuo 3-20-1, Ami, Inashiki, Ibaraki 300-0395, Japan
| | - Masashi Murakami
- Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Chuo 3-20-1, Ami, Inashiki, Ibaraki 300-0395, Japan
| | - Tadakuni Monma
- Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Chuo 3-20-1, Ami, Inashiki, Ibaraki 300-0395, Japan
| | - Hajime Ueda
- Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Chuo 3-20-1, Ami, Inashiki, Ibaraki 300-0395, Japan
| | - Makoto Tamamushi
- Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Chuo 3-20-1, Ami, Inashiki, Ibaraki 300-0395, Japan
| | - Naoki Konishi
- Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Chuo 3-20-1, Ami, Inashiki, Ibaraki 300-0395, Japan
| | - Sho-Ichiro Yara
- Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Chuo 3-20-1, Ami, Inashiki, Ibaraki 300-0395, Japan
| | - Takeshi Hirayama
- Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Chuo 3-20-1, Ami, Inashiki, Ibaraki 300-0395, Japan
| | - Tadashi Ikegami
- Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Chuo 3-20-1, Ami, Inashiki, Ibaraki 300-0395, Japan
| | - Akira Honda
- Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Chuo 3-20-1, Ami, Inashiki, Ibaraki 300-0395, Japan.,Joint Research Center, Tokyo Medical University Ibaraki Medical Center, Chuo 3-20-1, Ami, Inashiki, Ibaraki 300-0395, Japan
| | - Yuji Mizokami
- Department of Gastroenterology, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki 305-8577, Japan
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30
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Dinçer D, Ulukal Karancı E, Akın M, Adanır H. NSAID, antiaggregant, and/or anticoagulant-related upper gastrointestinal bleeding: Is there any change in prophylaxis rate after a 10-year period? TURKISH JOURNAL OF GASTROENTEROLOGY 2020; 30:505-510. [PMID: 31199288 DOI: 10.5152/tjg.2019.19057] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND/AIMS Using proton-pump inhibitor (PPI) is a protective option for patients who require long-term non-steroidal anti-inflammatory drugs (NSAIDs) and antiaggregants. In our previous study, the rate of PPI use in prophylaxis was found to be 2%. Here we aimed to investigate whether there is a change in PPI use in prophylaxis in a similar patient group after 10 years. MATERIALS AND METHODS The patients who followed up with upper gastrointestinal (GI) bleeding diagnosis between January 01, 2016 and December 31, 2017 were retrospectively evaluated. Patients who had malignancy or variceal hemorrhage were excluded. Ninety-six patients, who had taken NSAIDs, antiaggregants, or anticoagulants that were considered as the possible cause of bleeding, were included in the study. Risk groups for NSAID GI toxicity and PPI use rates in these patients were evaluated. RESULTS Twenty (21%) of all patients with upper GI bleeding were using PPI. According to the pre-bleeding risk factor assessment, 86% of the patients were found to have moderate to high risk for NSAID-related GI bleeding, and 81% of these patients were not using PPI. PPI prophylaxis was not provided to 15 (75%) of the 20 patients with previous history of peptic ulcer bleeding. CONCLUSION Despite many studies and recommendations on risk factors and prophylaxis for NSAID-related bleeding, prophylactic PPI use is still largely ignored by physicians. The rate of PPI use in the patient group of this study was found still quite insufficient.
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Affiliation(s)
- Dinç Dinçer
- Department of Gastroenterology, Akdeniz University School of Medicine, Antalya, Turkey
| | - Ece Ulukal Karancı
- Department of Internal Medicine, Akdeniz University School of Medicine, Antalya, Turkey
| | - Mete Akın
- Department of Gastroenterology, Akdeniz University School of Medicine, Antalya, Turkey
| | - Haydar Adanır
- Department of Gastroenterology, Akdeniz University School of Medicine, Antalya, Turkey
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31
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Scheiman JM. Commentary: cardioprotective aspirin and gastroduodenal ulcers. Aliment Pharmacol Ther 2020; 51:203. [PMID: 31850568 DOI: 10.1111/apt.15532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- James M Scheiman
- Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, VA, USA
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32
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Chao G, Ye F, Shen W, Gong W, Zhang S. Study on the characteristic of intestinal flora in patients with dual antiplatelet therapy. J Drug Target 2019; 28:500-507. [PMID: 31613141 DOI: 10.1080/1061186x.2019.1681433] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Objective: The objective of the study was to explore the intestinal flora in patients with dual antiplatelet therapy.Method: We collected fresh stool specimens from 10 patients receiving dual antiplatelet therapy and 10 healthy people as control group. Then, we extracted faecal DNA, amplified 16 s rNDA V3-V4 area, and applied Illumina Miseq to analyse the structure of intestinal flora.Result: At class level, DAPT group show higher abundance of class Bacilli and lower abundance of class Erysipelotrichia. At order level, the abundance of order Lactobacillales in DAPT group is higher (p < .05), while the abundance of order Erysipelotrichales is lower in DAPT group (p < .05). At family level, the abundance of family Streptococcaceae and family Lactobacillaceae in DAPT group is higher (p < .05), while the abundance of family Acidaminococcaceae and family Erysipelotrichaceae is lower in DAPT group (p < .05). At genus level, the abundance of genus Streptococcus and genus Klebsiella in DAPT group is higher (p < .05), while the abundance of genus Blautia, genus Phascolarctobacterium and genus Megamonas is lower in DAPT group (p < .05).Conclusion: Taking aspirin and clopidogrel will not cause a change in the biodiversity of intestinal flora. There are significant differences in the intestinal flora of DAPT group compared with the control group at class, order, family and genus level.
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Affiliation(s)
- Guanqun Chao
- Department of Family Medicine, Sir Run Run Shaw Hospital, Zhejiang University, China
| | - Fangxu Ye
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang Chinese Medical University, China
| | - Wei Shen
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang Chinese Medical University, China
| | - Wenqian Gong
- Department of Integrated Traditional Chinese and Western Medicine on Oncology, Ningbo Yinzhou People Hospital, Zhejiang, China
| | - Shuo Zhang
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang Chinese Medical University, China
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Affiliation(s)
- Emma Sverdén
- Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
- Department of Upper Gastrointestinal Surgery, South Hospital, Stockholm, Sweden
| | - Lars Agréus
- Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
- The University of Newcastle, Australia
| | - Jason M Dunn
- School of Cancer and Pharmaceutical Sciences, King's College London, and Guy's and St Thomas' NHS Foundation Trust, UK
| | - Jesper Lagergren
- Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
- School of Cancer and Pharmaceutical Sciences, King's College London, and Guy's and St Thomas' NHS Foundation Trust, UK
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Chitapanarux T, Lertprasertsuke N, Kongnak A. Teprenone for the prevention of low-dose aspirin-induced gastric mucosal injury in Helicobacter pylori-negative patients. Scand J Gastroenterol 2019; 54:1199-1204. [PMID: 31591940 DOI: 10.1080/00365521.2019.1672781] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Objectives: Low-dose aspirin is the standard treatment for the prevention of cardiovascular events in at-risk patients. We performed a randomized, placebo-controlled study to determine the efficacy of teprenone for primary prevention of gastrointestinal injury in patients taking LDA for vascular protection.Methods: Patients were eligible for enrollment if they required aspirin 100 mg/day. Aspirin- naïve patients without gastroduodenal ulcer and Helicobacter pylori infection were randomized to receive teprenone 150 mg/day or placebo for 12 weeks. Primary outcome was assessed by the incidence rate of gastroduodenal ulcer. Secondary outcomes were assessed by the incidence rate of gastric mucosal injury, the improvement in modified Lanza score (MLS), gastrointestinal symptom rating scale (GSRS) and the change of gastric immunohistochemical expression for COX-1.Results: Total of 130 patients were randomized, 64 in teprenone group and 66 in placebo group. There was no incidence of ulcer after 12 weeks in both groups. Incidence of gastric mucosal injury was higher in placebo group than in teprenone group (40.0 vs. 13.38%, p = .039). Mean change of MLS was higher in placebo group than in teprenone group (0.767 ± 0.467 vs. 0.271 ± 0.158, p = .003). Scores of mucosal edema, hyperemia and hemorrhage and the change of GSRS were not different between the two groups. Change of COX-1 immunoreactive score was higher in placebo group than in teprenone group (2.433 ± 1.476 vs. 1.233 ± 0.955, p = .001). There were no treatment-related adverse events.Conclusions: Teprenone is effective in preventing gastric mucosal injury in patients taking LDA. Preventive effects of teprenone on LDA-related gastroduodenal ulcers require further investigation.
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Affiliation(s)
- Taned Chitapanarux
- Gastrohepatology Unit, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.,Northern Thai Research Group of Radiation Oncology (NTRG-RO), Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Nirush Lertprasertsuke
- Department of Pathology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Acharaporn Kongnak
- Gastrohepatology Unit, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
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Shim KN, Kim JI, Kim N, Kim SG, Jo YJ, Hong SJ, Shin JE, Kim GH, Park KS, Choi SC, Kwon JG, Kim JH, Kim HJ, Kim JW. The efficacy and safety of irsogladine maleate in nonsteroidal anti-inflammatory drug or aspirin-induced peptic ulcer and gastritis. Korean J Intern Med 2019; 34:1008-1021. [PMID: 29847892 PMCID: PMC6718769 DOI: 10.3904/kjim.2017.370] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2017] [Revised: 01/28/2018] [Accepted: 02/21/2018] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND/AIMS Irsogladine maleate, an enhancer of gastric mucosal protective factors, has demonstrated its efficacy for various gastric mucosal injuries. The aim of this study was to evaluate the efficacy and safety of irsogladine for prevention of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin-induced peptic ulcer and gastritis. METHODS In this multicenter, randomized, double-blind, exploratory clinical trial, 100 patients over 50 years of age who needed continuous NSAIDs or aspirin for more than 8 weeks were randomly assigned to either test group (irsogladine maleate 2 mg, twice daily, 39 patients for full analysis) or placebo group (37 patients for full analysis). Primary outcomes were incidence of peptic ulcer and ratio of modified Lanza score (MLS) 2 to 4. Secondary outcome was the number of acute erosions confirmed by endoscopy at 8 weeks. Adverse effects were also compared. RESULTS There were no significant differences in gastric protective effects between test and placebo groups. However, two cases of peptic ulcer in the placebo group but none in the test group were observed. These two cases of peptic ulcer were Helicobacter pylori-negative. In addition, H. pylori-negative group showed significant changes in MLS score (p = 0.0247) and edema score (p = 0.0154) after the treatment compared to those before treatment in the test group. There was no significant difference in adverse events between the two groups. CONCLUSION The efficacy of irsogladine maleate was found in H. pylori-negative group, suggesting its potential as a protective agent against NSAIDs or aspirin-induced peptic ulcer and gastritis.
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Affiliation(s)
- Ki-Nam Shim
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Ewha Medical Research Institute, Seoul, Korea
| | - Jin Il Kim
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Sang Gyun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Yun Ju Jo
- Department of Internal Medicine, Eulji University School of Medicine, Seoul, Korea
| | - Su Jin Hong
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Jeong Eun Shin
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea
| | - Gwang Ha Kim
- Department of Internal Medicine, Pusan National University School of Medicine, and Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Kyung Sik Park
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Suck Chei Choi
- Department of Internal Medicine, Wonkwang University College of Medicine and Digestive Disease Research Institute, Iksan, Korea
| | - Joong Goo Kwon
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
| | - Jie-Hyun Kim
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hyun Jin Kim
- Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Ji Won Kim
- Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, Korea
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Lloyd BR, Leiman DA. An Updated Approach to Evaluation and Treatment of Helicobacter pylori Infection. South Med J 2019; 112:392-398. [PMID: 31282969 DOI: 10.14423/smj.0000000000000997] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Helicobacter pylori is a chronic bacterial infection that can lead to peptic ulcer disease, chronic gastritis, and gastric cancer. Its prevalence in the United States is lower than in most of the world, although specific populations are at particular risk for disease-related complications, including those with lower socioeconomic status and older adults. Since its discovery, there have been advances in H. pylori diagnosis and treatment, which are the focus of this review for general practice. Practice guidelines have expanded the role for treatment, despite traditional management algorithms resulting in diminished effectiveness as a result of increasing antibiotic resistance. In this context, new approaches warrant discussion. As such, this review aims to provide a clinical context and framework for the testing and rational treatment of H. pylori infection consistent with the available evidence.
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Affiliation(s)
- Benjamin R Lloyd
- From the Division of Gastroenterology, Duke University Medical Center, and Duke Clinical Research Institute, Durham, North Carolina
| | - David A Leiman
- From the Division of Gastroenterology, Duke University Medical Center, and Duke Clinical Research Institute, Durham, North Carolina
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Zhao J, Fan Y, Ye W, Feng W, Hu Y, Cai L, Lu B. The Protective Effect of Teprenone on Aspirin-Related Gastric Mucosal Injuries. Gastroenterol Res Pract 2019; 2019:6532876. [PMID: 31316561 PMCID: PMC6604287 DOI: 10.1155/2019/6532876] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Accepted: 11/28/2018] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVE Aspirin usage is associated with increased risk of gastrointestinal bleeding. The present study explored the potential of teprenone, an antiulcerative, in preventing aspirin-related gastric mucosal injuries. METHODS 280 patients with coronary diseases, naïve to aspirin medication, were admitted between 2011 and 2013 at the First Affiliated Hospital of Zhejiang Chinese Medical University and randomized into two groups (n = 140). The aspirin group received aspirin enteric-coated tablets 100 mg/day, while the aspirin+teprenone group received teprenone 50 mg 3 times/day along with aspirin. The patients were recorded for gastrointestinal symptoms and gastric mucosal injuries during a follow-up period of 12 months with 3-month intervals. RESULTS During the 3-month follow-up, no significant difference was observed in the incidence rate of gastrointestinal symptoms between the two groups (P = 0.498). However, the incidence rate of gastrointestinal symptoms was significantly lower in the aspirin+teprenone group than in the aspirin group during the follow-ups at 6 months (P = 0.036) and 12 months (P = 0.036). The incidence rate of gastric mucosal injuries in the aspirin group was significantly increased at 12 months compared to that at 3 months (P = 0.016). The incidence rates at 12 months and cumulative for the entire follow-up period in the aspirin+teprenone group were both significantly lower than those of the aspirin group (P = 0.049 and P = 0.001, respectively). CONCLUSION Long-term use of low-dose aspirin causes varying degrees of gastric mucosal damages and gastrointestinal symptoms; the severity will increase within a certain range with the extension of medication duration. Teprenone mitigates the gastrointestinal symptoms caused by low-dose aspirin, lowering both the incidence and severity of gastric mucosal injuries and exerting a positive protective effect.
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Affiliation(s)
- Jing Zhao
- Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, 54 Youdian Road, Hangzhou 310006, China
- Key Laboratory of Digestive Pathophysiology of Zhejiang Province, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Yihong Fan
- Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, 54 Youdian Road, Hangzhou 310006, China
- Key Laboratory of Digestive Pathophysiology of Zhejiang Province, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Wu Ye
- Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, 54 Youdian Road, Hangzhou 310006, China
| | - Wen Feng
- Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, 54 Youdian Road, Hangzhou 310006, China
| | - Yue Hu
- Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, 54 Youdian Road, Hangzhou 310006, China
- Key Laboratory of Digestive Pathophysiology of Zhejiang Province, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Lijun Cai
- Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, 54 Youdian Road, Hangzhou 310006, China
- Key Laboratory of Digestive Pathophysiology of Zhejiang Province, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Bin Lu
- Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, 54 Youdian Road, Hangzhou 310006, China
- Key Laboratory of Digestive Pathophysiology of Zhejiang Province, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
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Sarri GL, Grigg SE, Yeomans ND. Helicobacter pylori and low-dose aspirin ulcer risk: A meta-analysis. J Gastroenterol Hepatol 2019; 34:517-525. [PMID: 30408229 DOI: 10.1111/jgh.14539] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Revised: 10/25/2018] [Accepted: 10/30/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Owing to wide-spread use, low-dose aspirin (LDA) produces a substantial amount of peptic ulcer disease. Current guidelines are ambivalent about the need for Helicobacter pylori eradication to protect against LDA ulcers. This study aimed to determine, through meta-analysis, if (and by how much) infection alters the baseline risk of peptic ulcers during LDA therapy. METHODS Literature screening was performed in MEDLINE and EMBASE from inception to May 2018. Original studies reporting prevalence or incidence of uncomplicated ulcers in LDA users were included. Ulcer endpoints needed to be specified separately, according to H. pylori infection status. Meta-analysis was performed in MIX 2.0 Pro. RESULTS Ten cross-sectional studies and seven randomized controlled trials were included (n = 5964). The pooled odds ratios with 95% confidence intervals (CI) for the risk of LDA ulcers in H. pylori-positive versus H. pylori-negative individuals were 1.68 (95%CI 1.40-2.02) and 1.65 (95%CI 1.29-2.08) under fixed-effects and random-effects models, respectively. Heterogeneity among studies was minimal (I2 = 26.9%). After adjusting for the protective effects of antisecretory drugs, the odds ratios increased to 1.94 (95%CI 1.54-2.46). CONCLUSION This analysis suggests that H. pylori increases the risk of LDA ulcers by almost 70% in a population where some were taking proton pump inhibitors and/or other acid suppressants. Without antisecretory drugs, the risk almost doubles. Clinically, these findings may support the use of a test-and-treat approach to H. pylori in LDA users, particularly those already at higher risk of developing peptic ulcers.
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Affiliation(s)
- Gino L Sarri
- Melbourne School of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Sam E Grigg
- Melbourne School of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Neville D Yeomans
- Melbourne School of Medicine, University of Melbourne, Melbourne, Victoria, Australia.,Office for Research, Austin Health, Melbourne, Victoria, Australia
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Sugisaki N, Iwakiri R, Tsuruoka N, Sakata Y, Shimoda R, Fujimoto S, Eguchi Y, Fujimoto K. A case-control study of the risk of upper gastrointestinal mucosal injuries in patients prescribed concurrent NSAIDs and antithrombotic drugs based on data from the Japanese national claims database of 13 million accumulated patients. J Gastroenterol 2018; 53:1253-1260. [PMID: 29948304 DOI: 10.1007/s00535-018-1483-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Accepted: 06/05/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND We aimed to identify the adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and antithrombotics on the upper gastrointestinal (GI) mucosa in a clinical setting as a case-control study using a large-scale medical database in Japan. METHODS We evaluated the risk of upper GI mucosal injuries in patients receiving NSAIDs and antithrombotics using the Japan Medical Data Center claims database with data for 13 million accumulated patients, from January 2009 to December 2014. Endoscopically evaluated upper GI mucosal injuries were peptic ulcers (n = 143,271), upper GI bleeding (n = 10,545), and gastroesophageal reflux disease (n = 154,755). For each patient, ten controls were matched by age, sex, and diagnosis month. RESULTS The odds ratio (OR) for peptic ulcers was 1.45, 1.31, 1.50, 1.53, and 1.62; for upper GI bleeding: 1.76, 1.62, 1.96, 1.82, and 2.38; and for gastroesophageal reflux disease: 1.54, 1.41, 1.89, 1.67, and 1.91 for NSAIDs, COX-2 selective inhibitors, low-dose aspirin, antiplatelet drugs, and anticoagulants, respectively (all statistically significant: P < 0.001). Polypharmacy with NSAIDs and antithrombotic drugs increased the risk of upper GI injuries compared with single-drug therapy. The injury risk was also increased by lifestyle-related diseases, including diabetes mellitus and hyperlipidemia. CONCLUSIONS This case-control study using the large organized Japanese claims database provided the risk of upper GI mucosal injuries in patients receiving NSAIDs and antithrombotic drugs.
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Affiliation(s)
- Nobuyuki Sugisaki
- Graduate School of Medical Science, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
| | - Ryuichi Iwakiri
- Graduate School of Medical Science, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Nanae Tsuruoka
- Department of Internal Medicine, Saga University, Saga, 849-8501, Japan
| | - Yasuhisa Sakata
- Department of Internal Medicine, Saga University, Saga, 849-8501, Japan
| | - Ryo Shimoda
- Department of Internal Medicine, Saga University, Saga, 849-8501, Japan
| | - Shun Fujimoto
- Graduate School of Medical Science, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.,Department of Internal Medicine, Saga University, Saga, 849-8501, Japan
| | - Yuichiro Eguchi
- Graduate School of Medical Science, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.,Department of Internal Medicine, Saga University, Saga, 849-8501, Japan
| | - Kazuma Fujimoto
- Graduate School of Medical Science, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.,Department of Internal Medicine, Saga University, Saga, 849-8501, Japan
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Hunt R, B Lazebnik L, C Marakhouski Y, Manuc M, GN R, S Aye K, S Bordin D, V Bakulina N, S Iskakov B, A Khamraev A, M Stepanov Y, Ally R, Garg A. International Consensus on Guiding Recommendations for Management of Patients with Nonsteroidal Antiinflammatory Drugs Induced Gastropathy-ICON-G. Euroasian J Hepatogastroenterol 2018; 8:148-160. [PMID: 30828557 PMCID: PMC6395481 DOI: 10.5005/jp-journals-10018-1281] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Accepted: 11/28/2018] [Indexed: 12/24/2022] Open
Abstract
INTRODUCTION Nonsteroidal anti-inflammatory drugs (NSAIDs), one of the most commonly used medications worldwide, are frequently associated with gastrointestinal adverse events. Primary care physicians often face the challenge of achieving adequate pain relief with NSAIDs, while keeping their adverse events to a minimum. This is especially true when long-term use of NSAIDs is required such as in patients with osteoarthritis and rheumatoid arthritis. To help primary care physicians deal with such challenges more effectively, a panel of expert gastroenterologists came together with the aim of developing practice recommendations. METHODS A modified 'Delphi' process was used to reach consensus and develop practice recommendations. Twelve gastroenterologists from nine countries provided their expert inputs to formulate the recommendations. These recommendations were carefully developed taking into account existing literature, current practices, and expert opinion of the panelists. RESULTS The expert panel developed a total of fifteen practice recommendations. Following are the key recommendations: NSAIDs should be prescribed only when necessary; before prescribing NSAIDs, associated modifiable and non-modifiable risk factors should be considered; H. pylori infection should be considered and treated before initiating NSAIDs; patients should be properly educated regarding NSAIDs use; patients who need to be on long-term NSAIDs should be prescribed a gastroprotective agent, preferably a proton pump inhibitor and these patients should be closely monitored for any untoward adverse events. CONCLUSION/CLINICAL SIGNIFICANCE These practice recommendations will serve as an important tool for primary care physicians and will guide them in making appropriate therapeutic choices for their patients.How to cite this article: Hunt R, Lazebnik LB, Marakhouski YC, Manuc M, Ramesh GN, Aye KS, Bordin DS, Bakulina NV, Iskakov BS, Khamraev AA, Stepanov YM, Ally R, Garg A. International Consensus on Guiding Recommendations for Management of Patients with Nonsteroidal Anti-inflammatory Drugs Induced Gastropathy-ICON-G. Euroasian J Hepatogastroenterol, 2018;8(2):148-160.
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Affiliation(s)
- Richard Hunt
- Department of Medicine, McMaster University Health Science Centre, Hamilton, Ontario, Canada
| | - Leonid B Lazebnik
- Hospital Therapy, Moscow State University of Medicine and Dentistry, Moscow, Russian Federation
| | - Yury C Marakhouski
- Department of Gastroenterology and Nutrition, Belarusian Medical Academy of Postgraduate Education, Minsk, Belarus
| | - Mircea Manuc
- Clinic of Gastroenterology and Hepatology, Fundeni Clinical Institute, Bucharest, Romania
| | - Ramesh GN
- Centre of Excellence in Gastroenterology and Integrated Liver Care Aster Medi City, Cochin, Kerala, India
| | - Khin S Aye
- Department of Gastroenterology, University of Medicine, Yangon, Yangon Region, Myanmar
| | - Dmitry S Bordin
- Department of Pancreatic, Biliary tract and Upper GI disease, A.S. Loginov Moscow Clinical Scientific Center, Moscow, Russian Federation
| | - Natalia V Bakulina
- Department of Therapy and Clinical Pharmacology, North-Western State Medical University, Sankt-Peterburg, Russian Federation
| | - Baurzhan S Iskakov
- Department of Healthcare, Almaty Health Authority, Almaty, Almaty Province, Kazakhstan
| | - Abror A Khamraev
- Department of Gatroenterology, Tashkent Medical Academy, Tashkent, Tashkent Province, Uzbekistan
| | - Yurii M Stepanov
- Institute of Gastroenterology of National Academy of Medical Sciences of Ukraine, Dnipropetrovsk Dnipropetrovsk Oblast, Ukraine
| | - Reidwaan Ally
- Department of Gastroenterolgy, Wits University, Johannesburg, Gauteng, South Africa
| | - Amit Garg
- Department of Emerging Markets, Dr Reddy’s Laboratories Ltd, Hyderabad, Andhra Pradesh, India
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Al Khaja KAJ, Veeramuthu S, Isa HA, Sequeira RP. Prescription audit of NSAIDs and gastroprotective strategy in elderly in primary care. INTERNATIONAL JOURNAL OF RISK & SAFETY IN MEDICINE 2018; 29:57-68. [PMID: 28885223 DOI: 10.3233/jrs-170742] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND The use of non-steroidal anti-inflammatory drug (NSAIDs) is deemed a major risk factor for peptic ulcer disease in elderly population that requires concomitant therapy with gastroprotective agents (GPAs). OBJECTIVE This study evaluated the rational prescribing of NSAIDs and GPAs, and extent of adherence to the guideline recommendations in primary care. METHODS Nationwide audit of prescriptions issued to elderly patients (≥65 years) with hypertension or diabetic hypertension in primary care. RESULTS Among 2090 elderly, 45.9% were on low-dose aspirin, and 13.5% on other NSAIDs. Diclofenac-XR was the most frequently prescribed NSAIDs to three-quarter patients whereas naproxen, the safest NSAID for patients with high cardiovascular (CV) risk, was rarely prescribed. Among those on NSAID, 82.9% were on a scheduled dosing regimen; of these 78.8% received long-term NSAID therapy (3.9±0.9 months). The prescription rate of GPAs was low: 29.2% for aspirin and 33.3% for other NSAIDs. A quarter of the patients on histamine type-2 receptor antagonists received ranitidine at subtherapeutic single-dose for gastroprotection. Approximately half of the patients on proton pump inhibitors (PPIs) were prescribed supra-therapeutic double-dose regimen: omeprazole and esomeprazole accounted for 63.2% of overall prescribed PPIs. CONCLUSIONS The rational choice of NSAIDs and physicians' adherence to gastroprotective measures was suboptimal in primary care. The choice of NSAIDs and gastroprotective strategy in elderly be guided by the CV and gastrointestinal adverse events likelihood due to the NSAIDs and risk profile of patients for such adverse events.
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Affiliation(s)
- Khalid Ahmed Jassim Al Khaja
- Department of Pharmacology and Therapeutics, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain
| | - Sindhan Veeramuthu
- Department of Pharmacology and Therapeutics, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain
| | | | - Reginald Paul Sequeira
- Department of Pharmacology and Therapeutics, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain
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Lanza FL, Collaku A, Liu DJ. Endoscopic comparison of gastroduodenal injury with over-the-counter doses of new fast-dissolving ibuprofen and paracetamol formulations: a randomized, placebo-controlled, 4-way crossover clinical trial. Clin Exp Gastroenterol 2018; 11:169-177. [PMID: 29713191 PMCID: PMC5907787 DOI: 10.2147/ceg.s153231] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
Abstract
Background While gastrointestinal (GI) effects of standard ibuprofen and N-acetyl-p-aminophenol (APAP) have been reported, upper GI injury following treatment with fast-dissolving (FD) formulations of these analgesics has not been investigated. We evaluated upper GI effects of over-the-counter doses of 2 FD ibuprofen products and 1 FD-APAP product. Methods In a randomized, placebo-controlled, endoscopist-blinded, 4-way crossover study, 28 healthy subjects received FD ibuprofen 2×200 mg liquid capsules 3 times daily (TID), ibuprofen 2×200 mg tablets TID, FD-APAP 2×500 mg tablets 4 times daily (QID), and placebo 2×500 mg tablets QID for 7 days. The primary end point was gastric mucosal damage assessed by endoscopy using the Lanza scale: 0=normal stomach or proximal duodenum, 1=mucosal hemorrhages only, 2=1 or 2 erosions, 3=numerous (3-10) erosions, and 4=large number of erosions (>10) or ulcer. Secondary end points included duodenal mucosal damage (Lanza scale); gastroduodenal mucosal injury, classified as present (gastric and/or duodenal endoscopy score ≥2) or absent (gastric and/or duodenal endoscopy score <2); and number of hemorrhages, erosions, and ulcers counted separately in the stomach and duodenum. Results Significantly greater gastric mucosal injury was observed after treatment with both ibuprofen products vs FD-APAP (p<0.0001 and p=0.0095, respectively). FD-APAP showed no difference from placebo (p=0.4794). The odds of having an incidence of gastroduodenal mucosal injury were over 6 times greater from FD ibuprofen liquid capsule treatment (odds ratio [OR]=6.19, 95% confidence interval [CI]: 1.60, 23.97) and over 3 times greater from ibuprofen tablet treatment (OR=3.19, 95% CI: 0.8, 12.74) vs FD-APAP. Conclusion Treatment with 2 ibuprofen products was associated with significant gastric mucosal injury. Of the 4 treatments studied, FD ibuprofen liquid capsules had the highest risk of incidence of gastroduodenal mucosal injury. Treatment with FD-APAP did not induce any clinically or statistically significant gastroduodenal mucosal injury.
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Affiliation(s)
- Frank L Lanza
- Department of Gastroenterology, Houston Institute for Clinical Research, Houston, TX, USA
| | - Agron Collaku
- Biostatistics Department, GlaxoSmithKline Consumer Healthcare, Parsippany, NJ, USA
| | - Dongzhou J Liu
- Global Clinical Development, GlaxoSmithKline, Collegeville, PA, USA
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Verma S, Kumar VL. Artesunate affords protection against aspirin–induced gastric injury by targeting oxidative stress and proinflammatory signaling. Pharmacol Rep 2018; 70:390-397. [PMID: 29397336 DOI: 10.1016/j.pharep.2017.06.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2017] [Revised: 05/02/2017] [Accepted: 06/13/2017] [Indexed: 12/13/2022]
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Koh JS, Joo MK. The Role of Helicobacter pylori Infection in Drug-induced Peptic Ulcer. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2018. [DOI: 10.7704/kjhugr.2018.18.2.89] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Jin Sung Koh
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Moon Kyung Joo
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
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Aspirin Use in Secondary Cardiovascular Protection and the Development of Aspirin-Associated Erosions and Ulcers. J Cardiovasc Pharmacol 2017; 68:121-6. [PMID: 27002280 DOI: 10.1097/fjc.0000000000000387] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Aspirin for secondary cardiovascular disease prevention is well established, but treatment discontinuation, often because of gastrointestinal mucosal injury or symptoms, can lead to increased risk for cardiovascular events. Proton pump inhibitor therapy is recommended for aspirin-treated patients at gastrointestinal risk. PA32540 [enteric-coated aspirin (EC-ASA) 325 mg + immediate-release omeprazole 40 mg] was compared with EC-ASA 325 mg alone once daily for 6 months in 2 duplicate, randomized double-blind trials in gastrointestinal-risk patients taking aspirin for ≥3 months for secondary prevention. In this post hoc analysis, we determined the prevalence of endoscopic upper gastrointestinal ulcers at screening and whether baseline endoscopic gastric erosions impacted subsequent ulcer development. At the screening endoscopy, 6% of subjects had upper gastrointestinal ulcers (not eligible for randomization) and 40% had gastric erosions. Conditional logistic regression modeling showed that baseline gastric erosions are significantly associated with endoscopic gastric ulcer development (OR = 2.12, 95% confidence interval, 1.26-3.57). In subjects with baseline gastric erosion, 4.2% of PA32540-treated versus 13.0% of EC-ASA-treated subjects (P = 0.001) subsequently developed endoscopic gastric ulcers. These data suggest that gastric injury predisposes to gastric ulcer development when taking EC-ASA, and exposure to immediate-release omeprazole in the presence of aspirin therapy significantly reduces the likelihood of progressing to gastric ulcers.
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Negovan A, Iancu M, Moldovan V, Sàrkàny K, Bataga S, Mocan S, Țilea I, Banescu C. The contribution of clinical and pathological predisposing factors to severe gastro-duodenal lesions in patients with long-term low-dose aspirin and proton pump inhibitor therapy. Eur J Intern Med 2017; 44:62-66. [PMID: 28576397 DOI: 10.1016/j.ejim.2017.05.017] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2016] [Revised: 05/16/2017] [Accepted: 05/17/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND Preventive strategies developed to avoid the complications of antiplatelet therapies recommend the evaluation of risk factors for gastrointestinal events and indicated gastroprotective strategies. AIM We aimed to assess the impact of predisposing factors - histological findings, concomitant drug consumption, comorbidities, symptoms, social habits, Helicobacter pylori infection - on severe gastro-duodenal lesions in patients with low-dose aspirin and concomitant protective therapy with proton pump inhibitors (PPI). METHOD We enrolled 237 patients with LDA and PPI therapy, referred for upper digestive endoscopy, divided into two groups according to the severity of their endoscopic lesions (172 patients with no or mild endoscopic lesions and 65 patients with severe endoscopic lesions). RESULTS In the univariate logistic regression model, the factors associated with severe gastro-duodenal lesions were gender (OR=1.87, 95% CI: 1.04-3.41), anticoagulants (OR=2.40, 95% CI: 1.26-4.53), gastric atrophy and/or intestinal metaplasia (OR=1.85, 95% CI: 1.04-3.32), congestive heart failure (OR=2.59, 95% CI: 1.16-6.62), anaemia (OR=3.01, 95% CI: 1.67-5.47) and smoking (OR=4.29, 95% CI: 1.57-12.32). In the final model, anticoagulants (p=0.041<0.05) and anaemia (p=0.019<0.05) were risk factors for severe lesions via multivariate regression analysis, while for active/inactive chronic gastritis and smoking a positive dependency with a tendency towards statistical significance (p<0.10) was noticed for severe gastric lesions. CONCLUSIONS In patients treated with low-dose aspirin and gastroprotective therapy with proton pump inhibitors we have enough evidence to consider co-treatment with anticoagulants and anaemia important predictors for severe endoscopic lesions, while other factors such as inflammation in gastric biopsies, congestive heart failure, co-treatment with clopidogrel and smoking tended to have a positive influence on risk for severe gastro-duodenal lesions.
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Affiliation(s)
- Anca Negovan
- University of Medicine and Pharmacy, Clinical Science-Internal Medicine, Gheorghe Marinescu 38, Tirgu Mureș 540139, Romania
| | - Mihaela Iancu
- University of Medicine and Pharmacy "Iuliu Hațieganu", Department of Medical Informatics and Biostatistics, Louis Pasteur St, no. 6, 400349 Cluj-Napoca, Romania.
| | - Valeriu Moldovan
- University of Medicine and Pharmacy, Morphological Science, Gheorghe Marinescu 38, Tirgu Mureș 540139, Romania
| | - Kinga Sàrkàny
- Emergency County Hospital, IIIrd Medical Clinic, Gheorghe Marinescu 50, Tirgu Mures 540136, Mures, Romania
| | - Simona Bataga
- University of Medicine and Pharmacy, Clinical Science-Internal Medicine, Gheorghe Marinescu 38, Tirgu Mureș 540139, Romania
| | - Simona Mocan
- Emergency County Hospital, Pathological Department, Gheorghe Marinescu 50, Tirgu Mures 540136, Mures, Romania
| | - Ioan Țilea
- University of Medicine and Pharmacy, Clinical Science-Internal Medicine, Gheorghe Marinescu 38, Tirgu Mureș 540139, Romania
| | - Claudia Banescu
- University of Medicine and Pharmacy, Morphological Science, Gheorghe Marinescu 38, Tirgu Mureș 540139, Romania
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Are the Symptoms of an NSAID-Induced Ulcer Truly Milder Than Those of an Ordinary Ulcer? Gastroenterol Res Pract 2017; 2017:4653250. [PMID: 29129973 PMCID: PMC5654275 DOI: 10.1155/2017/4653250] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2017] [Accepted: 07/18/2017] [Indexed: 12/14/2022] Open
Abstract
Objective The percentage of patients with nonsteroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin- (LDA-) induced ulcers who complain of gastrointestinal symptoms has generally been considered to be low. The aim of this study was to examine and compare the symptoms and quality of life (QOL) at peptic ulcer onset. Methods This study involved 200 patients who were confirmed by endoscopy to be in the acute stage of gastroduodenal ulcer (A1-H1). Patients completed a self-administered questionnaire (Global Overall Symptom score and SF-8) at ulcer onset, and data were compared between NSAIDs/LDA ulcers and non-NSAIDs/LDA ulcers. Results The upper gastrointestinal symptoms score was significantly lower for patients using LDA only (20.5 ± 9.4 in the nonusing group, 19.6 ± 8.6 in the NSAIDs-only group, 16.7 ± 11.6 in the LDA-only group, and 18.5 ± 7.2 in the NSAIDs/LDA group, P < 0.05). The QOL score (physical summary) was significantly lower in the NSAID group (42.1 ± 9.9) than in the nonusing group (47.6 ± 7.6) (P < 0.05). Patients' characteristics showed no significant differences among the groups, with the exception of age. Conclusion The severity of upper abdominal symptoms at peptic ulcer onset was similar between NSAID users and nonusers.
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Park SM, Jeong H, Jung MH, Hong KS, Hong MK, Bang CS, Kim CY. Rationale and Design for a Randomized Comparison of Efficacy and Safety between Aspirin and Clopidogrel in Atrial Fibrillation Patients with Low Stroke Risk: CESAC-AF trial. Contemp Clin Trials 2017. [PMID: 28642210 DOI: 10.1016/j.cct.2017.06.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND Atrial fibrillation (AF) increases the risk of thromboembolic stroke. An oral anticoagulant should be administrated to prevent stroke in patients with moderate stroke risk (ie, CHA2DS2-VASc score>2). If the stroke risk is low (i.e. the score=1), however, antiplatelet agent such as aspirin is widely used. Aspirin can cause peptic ulcer disease (PUD) while its alternative, clopidogrel, theoretically does not. OBJECTIVE To elucidate the efficacy and safety between aspirin and clopidogrel, a multicenter randomized controlled trial was designed in AF patients with low stroke risk. METHODS According to sample size estimation based on previous literature, a total of 1560 AF patients with low stroke risk will be randomly assigned into 4 different groups dependent upon initial esophagogastroduodenoscopy (EGD) results: two mono-antiplatelet treatment groups with either aspirin 100mg or clopidogrel 75mg for 1year; two antiplatelet agent and proton pump inhibitor (PPI) combination groups. Follow-up EGD will be performed at 1year. RESULTS The clinical follow-up will be performed for 1year after enrollment. The primary efficacy endpoint is to compare the annual stroke rate between aspirin and clopidogrel treatment groups. The primary safety endpoint is to compare the prevalence of drug-induced gastrointestinal (GI) and intracranial hemorrhage and upper-GI response including PUD based on EGD after 1year. CONCLUSIONS This trial will determine whether clopidogrel is noninferior in stroke prevention and superior in reduction of GI events including PUD to aspirin in AF patients with low stroke risk. (ClinicalTrials.gov: NCT02960126).
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Affiliation(s)
- Sang Min Park
- Cardiovascular Center, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Republic of Korea; Department of Medicine, the Graduate School of Yonsei University, Seoul, Republic of Korea.
| | - Haemin Jeong
- Cardiovascular Center, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Republic of Korea
| | - Mi-Hyang Jung
- Cardiovascular Center, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Republic of Korea
| | - Kyung Soon Hong
- Cardiovascular Center, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Republic of Korea
| | - Myeong-Ki Hong
- Division of Cardiology, Yonsei Cardiovascular Center, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Chang Seok Bang
- Division of Gastroenterology, Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Republic of Korea
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Cho JH, Choi JS, Chun SW, Lee S, Han KJ, Kim HM. The IL-1B Genetic Polymorphism Is Associated with Aspirin-Induced PepticUlcers in a Korean Ethnic Group. Gut Liver 2017; 10:362-8. [PMID: 26601827 PMCID: PMC4849688 DOI: 10.5009/gnl15129] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background/Aims Single nucleotide polymorphisms (SNPs) are associated with aspirin-induced peptic ulcers. However, SNPs of specific genes vary among races, and data regarding SNPs in the Korean population are scarce. In this study, we aimed to investigate the relationships between SNPs of the COX-1, IL-1β, IL-1RN, and TNF genes and aspirin-induced peptic ulcers, as pilot research in a Korean population. Methods Patients who had been taking low-dose aspirin (100 mg) for at least 4 weeks were prospectively enrolled. DNA was extracted from whole blood, and DNA sequencing was subsequently performed. Results A total of 48 patients were enrolled (23 peptic ulcer patients vs 25 nonulcer controls). Three exon SNPs (IL-1β -581C/T [rs1143627], IL-1β -1061C/T [rs16944], and IL-1RN -1129 [rs4251961]) and one intron SNP (IL-1β IVS2+242C/T) were significantly different between the two groups. On the multivariate analysis after adjustments for age and sex, the CC/CT genotypes of IL-1β -581C/T, and the CT/TT genotypes of IL-1β -1061C/T were positively associated with aspirin-induced peptic ulcers (odds ratio [OR], 4.6, 95% confidence interval [CI], 1.054 to 20.303, p=0.04; OR, 4.6, 95% CI, 1.054 to 20.303, p=0.04). Conclusions The IL-1β -581C/T and IL-1β -1061C/T genotypes may be associated with low-dose aspirin-induced peptic ulcers in a Korean ethnic group.
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Affiliation(s)
- Jae Hee Cho
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Ja Sung Choi
- Department of Internal Medicine, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon, Korea
| | - Song Wook Chun
- Division of Gastroenterology, Department of Internal Medicine, Myongji Hospital, Goyang, Korea
| | - Sangheun Lee
- Department of Internal Medicine, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon, Korea
| | - Ki Jun Han
- Department of Internal Medicine, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon, Korea
| | - Hee Man Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
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García-Rayado G, Sostres C, Lanas A. Aspirin and omeprazole for secondary prevention of cardiovascular disease in patients at risk for aspirin-associated gastric ulcers. Expert Rev Clin Pharmacol 2017; 10:875-888. [PMID: 28463532 DOI: 10.1080/17512433.2017.1324782] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Cardiovascular disease is the most important cause of morbidity and mortality in the world and low-dose aspirin is considered the cornerstone of the cardiovascular disease prevention. However, low-dose aspirin use is associated with gastrointestinal adverse effects in the whole gastrointestinal tract. In this setting, co-therapy with a proton pump inhibitor is the most accepted strategy to reduce aspirin related upper gastrointestinal damage. In addition, some adverse effects have been described with proton pump inhibitors long term use. Areas covered: Low-dose aspirin related beneficial and adverse effects in cardiovascular system and gastrointestinal tract are reviewed. In addition, this manuscript summarizes current data on upper gastrointestinal damage prevention and adverse events with proton pump inhibition. Finally, we discuss the benefit/risk ratio of proton pump inhibitor use in patients at risk of gastrointestinal damage taking low-dose aspirin. Expert commentary: Nowadays, with the current available evidence, the combination of low-dose aspirin with proton pump inhibitor is the most effective therapy for cardiovascular prevention in patients at high gastrointestinal risk. However, further studies are needed to discover new effective strategies with less related adverse events.
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Affiliation(s)
- Guillermo García-Rayado
- a Service of Digestive Diseases , University Clinic Hospital Lozano Blesa , Zaragoza , Spain.,b Aragón Health Research Institute (IIS Aragón) , Zaragoza , Spain
| | - Carlos Sostres
- a Service of Digestive Diseases , University Clinic Hospital Lozano Blesa , Zaragoza , Spain.,b Aragón Health Research Institute (IIS Aragón) , Zaragoza , Spain.,c CIBERehd , Madrid , Spain.,d University of Zaragoza , Zaragoza , Spain
| | - Angel Lanas
- a Service of Digestive Diseases , University Clinic Hospital Lozano Blesa , Zaragoza , Spain.,b Aragón Health Research Institute (IIS Aragón) , Zaragoza , Spain.,c CIBERehd , Madrid , Spain.,d University of Zaragoza , Zaragoza , Spain
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