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Zhang X, Xiao X, Chen PR, Li YN, Lv XH, Yang JL. Proton Pump Inhibitors Increase the Risk of Nonsteroidal Anti-inflammatory Drug-Related Small-Bowel Injury: A Systematic Review With Meta-analysis. Clin Transl Gastroenterol 2023; 14:e00588. [PMID: 37019683 PMCID: PMC10299777 DOI: 10.14309/ctg.0000000000000588] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Accepted: 03/28/2023] [Indexed: 04/07/2023] Open
Abstract
INTRODUCTION Conflicting results exist on the association between proton-pump inhibitor (PPI) and nonsteroidal anti-inflammatory drug (NSAID)-related small-bowel damage. The aim of this study was to determine whether PPIs increased the risk of NSAID-related small-bowel damage by meta-analysis. METHODS A systematic electronic search in PubMed, Embase, and Web of Science was conducted from the time the database was created until March 31, 2022, for studies reporting associations between PPI use and outcomes, including the endoscopy-verified prevalence of small-bowel injury, mean number of small-bowel injuries per patient, change in hemoglobin level, and risk of small-bowel bleeding in subjects taking NSAIDs. Meta-analytical calculations for odds ratio (OR) and mean difference (MD) were performed with the random-effects model and interpreted with 95% confidence intervals (CIs). RESULTS Fourteen studies comprising 1996 subjects were included. Pooled analysis demonstrated that concomitant use of PPIs significantly increased the prevalence and number of endoscopy-verified small-bowel injuries (prevalence: OR = 3.00; 95% CI: 1.74-5.16; number: MD = 2.30; 95% CI: 0.61-3.99) and decreased hemoglobin levels (MD = -0.50 g/dL; 95% CI: 0.88 to -0.12) in NSAID users but did not change the risk of small-bowel bleeding (OR = 1.24; 95% CI: 0.80-1.92). Subgroup analysis demonstrated that PPIs significantly increased the prevalence of small-bowel injury in subjects taking nonselective NSAIDs (OR = 7.05; 95% CI: 4.70-10.59, 4 studies, I 2 = 0) and COX-2 inhibitors (OR = 4.00; 95% CI: 1.18-13.60, 1 study, no calculated I 2 ) when compared with COX-2 inhibitors alone. DISCUSSION PPIs increased the risk of NSAID-related small-bowel damage, and the clinical significance of higher prevalence of small-bowel injuries should be studied in the future.
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Affiliation(s)
- Xian Zhang
- Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, Department of Gastroenterology & Hepatology, West China Hospital, Sichuan, University, Chengdu, China
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China;
| | - Xue Xiao
- Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, Department of Gastroenterology & Hepatology, West China Hospital, Sichuan, University, Chengdu, China
- Department of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, China
| | - Ping-Run Chen
- Department of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, China
| | - Yi-Na Li
- Department of Respiratory Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Xiu-He Lv
- Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, Department of Gastroenterology & Hepatology, West China Hospital, Sichuan, University, Chengdu, China
- Department of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, China
| | - Jin-Lin Yang
- Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, Department of Gastroenterology & Hepatology, West China Hospital, Sichuan, University, Chengdu, China
- Department of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, China
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Zhou M, Zhang J, Liu J, Smith SC, Ma C, Ge J, Huo Y, Fonarow GC, Liu J, Hao Y, Gao F, Sun Y, Morgan L, Yang N, Hu G, Zeng Y, Han Y, Zhao D. Proton Pump Inhibitors and In-Hospital Gastrointestinal Bleeding in Patients With Acute Coronary Syndrome Receiving Dual Antiplatelet Therapy. Mayo Clin Proc 2022; 97:682-692. [PMID: 35164933 DOI: 10.1016/j.mayocp.2021.11.037] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 09/12/2021] [Accepted: 11/19/2021] [Indexed: 12/21/2022]
Abstract
OBJECTIVE To evaluate the association between proton pump inhibitor (PPI) use and in-hospital gastrointestinal (GI) bleeding in patients with acute coronary syndrome (ACS) taking dual antiplatelet therapy (DAPT). PATIENTS AND METHODS This study is based on the Improving Care for Cardiovascular Disease in China-ACS project, an ongoing collaborative registry and quality improvement project of the American Heart Association and the Chinese Society of Cardiology. A total of 25,567 patients with ACS taking DAPT from 172 hospitals from July 1, 2017, through December 31, 2018, were included. Multivariable Cox regression and propensity score-matched analyses were used to evaluate the association between PPI use and in-hospital GI bleeding. RESULTS Of these patients with ACS, 63.9% (n=16,332) were prescribed PPIs within 24 hours of admission. Patients using PPIs had a higher rate of GI bleeding compared with those not using PPIs (1.0% vs 0.5%; P<.001). In the multivariable Cox regression analysis, early PPI use was associated with a 58% higher risk of GI bleeding (hazard ratio, 1.58; 95% CI, 1.15 to 2.18; P=.005). Further propensity score matching attenuated the association but still showed that patients using PPIs had a higher rate of GI bleeding (0.8% vs 0.6%; P=.04). CONCLUSION In China, PPIs are widely used within 24 hours of admission in patients with ACS taking DAPT. An increased risk of GI bleeding is observed in inpatients with early PPI use. Randomized trials on early use of PPIs in patients with ACS receiving DAPT are warranted. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02306616.
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Affiliation(s)
- Mengge Zhou
- Department of Epidemiology, Beijing Anzhen Hospital, Capital Medical University, the Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, China; Vanke School of Public Health, Tsinghua University
| | - Jie Zhang
- Department of Gastroenterology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Jing Liu
- Department of Epidemiology, Beijing Anzhen Hospital, Capital Medical University, the Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, China
| | - Sidney C Smith
- Division of Cardiology, University of North Carolina, Chapel Hill
| | - Changsheng Ma
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Junbo Ge
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yong Huo
- Department of Cardiology, Peking University First Hospital, Beijing, China
| | - Gregg C Fonarow
- Division of Cardiology, Geffen School of Medicine at University of California, Los Angeles
| | - Jun Liu
- Department of Epidemiology, Beijing Anzhen Hospital, Capital Medical University, the Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, China
| | - Yongchen Hao
- Department of Epidemiology, Beijing Anzhen Hospital, Capital Medical University, the Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, China
| | - Feng Gao
- Department of Gastroenterology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Yamei Sun
- Department of Gastroenterology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Louise Morgan
- International Quality Improvement Department, American Heart Association, Dallas, TX
| | - Na Yang
- Department of Epidemiology, Beijing Anzhen Hospital, Capital Medical University, the Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, China
| | - Guoliang Hu
- Department of Epidemiology, Beijing Anzhen Hospital, Capital Medical University, the Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, China
| | - Yuhong Zeng
- Department of Epidemiology, Beijing Anzhen Hospital, Capital Medical University, the Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, China
| | - Yaling Han
- Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning, China.
| | - Dong Zhao
- Department of Epidemiology, Beijing Anzhen Hospital, Capital Medical University, the Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, China.
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Chao G, Dai J, Zhang S. Protective effect of naringin on small intestine injury in NSAIDs related enteropathy by regulating ghrelin/GHS-R signaling pathway. Life Sci 2020; 266:118909. [PMID: 33333047 DOI: 10.1016/j.lfs.2020.118909] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Revised: 11/16/2020] [Accepted: 12/08/2020] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To investigate the mechanism of Ghrelin/GHS-R signaling pathway in small intestine injury induced by NSAIDs related enteropathy. To clarify the mechanism network of intestinal mucosal repair with naringin as a new therapeutic method. METHODS Naringin was used as the intervention method, observed the damage of small intestinal mucosa and detected the expression of ghrelin, GHS-R, leptin and TNF-α by electron microscopy, HE staining and immunohistochemistry. RESULTS Compared with the control group, the weight of rats in the model group decreased, the thickness of intestinal mucosa became thinner, the structure of intestinal mucosa changed, the expression of ghrelin, GHS-R and leptin decreased, the expression of TNF-α increased. Compared with the model group, the intestinal mucosa of the treatment group was repaired, the expression of ghrelin, GHS-R and leptin was increased, and the expression TNF-α was decreased. CONCLUSION The mechanism of intestinal mucosal damage in patients with NSAIDs related enteropathy may be related to the decreased expression of ghrelin, GHS-R and leptin, and promotion of TNF-α secretion. Naringin can effectively promote the secretion of ghrelin and leptin, the expression of GSH-R, and inhibit the release of TNF-α, so as to repair intestinal mucosa naringin will become a new method to treat and prevent NSAIDs related intestinal diseases.
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Affiliation(s)
- Guanqun Chao
- Department of General Practice, Sir Run Run Shaw Hospital, Zhejiang University, China.
| | - Jian Dai
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang Chinese Medical University, China
| | - Shuo Zhang
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang Chinese Medical University, China.
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Patrono C. The Multifaceted Clinical Readouts of Platelet Inhibition by Low-Dose Aspirin. J Am Coll Cardiol 2015; 66:74-85. [PMID: 26139061 DOI: 10.1016/j.jacc.2015.05.012] [Citation(s) in RCA: 95] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2015] [Revised: 04/21/2015] [Accepted: 05/05/2015] [Indexed: 12/14/2022]
Abstract
Inactivation of platelet cyclooxygenase (COX)-1 by low-dose aspirin leads to long-lasting suppression of thromboxane (TX) A2 production and TXA2-mediated platelet activation and aggregation. This effect is necessary and sufficient to explain aspirin's unique (among other COX-1 inhibitors) effectiveness in preventing atherothrombosis, as well as its shared (with other antiplatelet agents) bleeding liability. However, different mechanisms of action have been suggested to explain other beneficial effects of aspirin, such as prevention of venous thromboembolism, chemoprevention of colorectal (and other) cancers, and reduced risk of dementia. These mechanisms include acetylation of other proteins in blood coagulation, inhibition of COX-2 activity, and other COX-independent mechanisms. The intent of this review is to develop the concept that the multifaceted therapeutic effects of low-dose aspirin may reflect pleiotropic consequences of platelet inhibition on pathophysiological tissue repair processes. Furthermore, the clinical implications of this concept will be discussed in terms of current clinical practice and future research.
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Affiliation(s)
- Carlo Patrono
- Department of Pharmacology, Catholic University School of Medicine, Rome, Italy.
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