Acute Middle Gastrointestinal Bleeding Risk Associated with NSAIDs, Antithrombotic Drugs, and PPIs: A Multicenter Case-Control Study
Middle gastrointestinal bleeding (MGIB) risk has not been fully investigated due to its extremely rare occurrence and the need for multiple endoscopies to exclude upper and lower gastrointestinal bleeding. This study investigated whether MGIB is associated with the use of non-steroidal anti-inflamma...
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| Veröffentlicht in: | PloS one 2016-03, Vol.11 (3), p.e0151332-e0151332 |
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| creator | Nagata, Naoyoshi Niikura, Ryota Yamada, Atsuo Sakurai, Toshiyuki Shimbo, Takuro Kobayashi, Yuka Okamoto, Makoto Mitsuno, Yuzo Ogura, Keiji Hirata, Yoshihiro Fujimoto, Kazuma Akiyama, Junichi Uemura, Naomi Koike, Kazuhiko |
| description | Middle gastrointestinal bleeding (MGIB) risk has not been fully investigated due to its extremely rare occurrence and the need for multiple endoscopies to exclude upper and lower gastrointestinal bleeding. This study investigated whether MGIB is associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin (LDA), thienopyridines, anticoagulants, and proton-pump inhibitors (PPIs), and whether PPI use affects the interactions between MGIB and antithrombotic drugs.
In this multicenter, hospital-based, case-control study, 400 patients underwent upper and lower endoscopy, 80 had acute overt MGIB and 320 had no bleeding and were matched for age and sex as controls (1:4). MGIB was additionally evaluated by capsule and/or double-balloon endoscopy, after excluding upper and lower GI bleeding. Adjusted odds ratios (AOR) for MGIB risk were calculated using conditional logistic regression. To estimate the propensity score, we employed a logistic regression model for PPI use.
In patients with MGIB, mean hemoglobin level was 9.4 g/dL, and 28 patients (35%) received blood transfusions. Factors significantly associated with MGIB were chronic kidney disease (p |
| doi_str_mv | 10.1371/journal.pone.0151332 |
| format | Article |
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In this multicenter, hospital-based, case-control study, 400 patients underwent upper and lower endoscopy, 80 had acute overt MGIB and 320 had no bleeding and were matched for age and sex as controls (1:4). MGIB was additionally evaluated by capsule and/or double-balloon endoscopy, after excluding upper and lower GI bleeding. Adjusted odds ratios (AOR) for MGIB risk were calculated using conditional logistic regression. To estimate the propensity score, we employed a logistic regression model for PPI use.
In patients with MGIB, mean hemoglobin level was 9.4 g/dL, and 28 patients (35%) received blood transfusions. Factors significantly associated with MGIB were chronic kidney disease (p<0.001), liver cirrhosis (p = 0.034), NSAIDs (p<0.001), thienopyridines (p<0.001), anticoagulants (p = 0.002), and PPIs (p<0.001). After adjusting for these factors, NSAIDs (AOR, 2.5; p = 0.018), thienopyridines (AOR, 3.2; p = 0.015), anticoagulants (AOR, 4.3; p = 0.028), and PPIs (AOR; 2.0; p = 0.021) were independently associated with MGIB. After adjusting for propensity score, the use of PPIs remained an independent risk factors for MGIB (AOR, 1.94; p = 0.034). No significant interactions were observed between PPIs and NSAIDs (AOR, 0.7; p = 0.637), LDA (AOR, 0.3; p = 0.112), thienopyridine (AOR, 0.7, p = 0.671), or anticoagulants (AOR, 0.5; p = 0.545).
One-third of patients with acute small intestinal bleeding required blood transfusion. NSAIDs, thienopyridines, anticoagulants, and PPIs increased the risk of acute small intestinal bleeding. However, there were no significant interactions found between antithrombotic drugs and PPI use for bleeding risk.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0151332</identifier><identifier>PMID: 26978517</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Analysis ; Anti-inflammatory agents ; Anti-Inflammatory Agents, Non-Steroidal - adverse effects ; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use ; Anticoagulants ; Anticoagulants - adverse effects ; Anticoagulants - therapeutic use ; Aspirin ; Aspirin - adverse effects ; Aspirin - therapeutic use ; Balloon treatment ; Biology and Life Sciences ; Bleeding ; Blood ; Blood transfusion ; Case studies ; Case-Control Studies ; Cirrhosis ; Colonoscopy ; Departments ; Dosage and administration ; Drug dosages ; Drug therapy ; Drugs ; Endoscopy ; Female ; Gastroenterology ; Gastrointestinal Hemorrhage - chemically induced ; Health risk assessment ; Hemoglobin ; Hemorrhage ; Hepatology ; Hospitals ; Humans ; Inflammation ; Intestinal diseases ; Intestine ; Liver ; Liver cirrhosis ; Liver diseases ; Male ; Medical screening ; Medicine ; Medicine and Health Sciences ; Middle Aged ; Nonsteroidal anti-inflammatory agents ; Nonsteroidal anti-inflammatory drugs ; Patients ; Platelet Aggregation Inhibitors - adverse effects ; Platelet Aggregation Inhibitors - therapeutic use ; Proton pump inhibitors ; Proton Pump Inhibitors - adverse effects ; Proton Pump Inhibitors - therapeutic use ; Regression models ; Retrospective Studies ; Risk analysis ; Risk Factors ; Studies ; Thienopyridines ; Transfusion ; Young Adult</subject><ispartof>PloS one, 2016-03, Vol.11 (3), p.e0151332-e0151332</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Nagata et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Nagata et al 2016 Nagata et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-7cb84035f62a62bf5ea5a0127c2c8b2c3429097f03db17c53d8d7f0e9f0829333</citedby><cites>FETCH-LOGICAL-c692t-7cb84035f62a62bf5ea5a0127c2c8b2c3429097f03db17c53d8d7f0e9f0829333</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792424/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792424/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2919,23857,27915,27916,53782,53784,79361,79362</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26978517$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Grolmusz, Vince</contributor><creatorcontrib>Nagata, Naoyoshi</creatorcontrib><creatorcontrib>Niikura, Ryota</creatorcontrib><creatorcontrib>Yamada, Atsuo</creatorcontrib><creatorcontrib>Sakurai, Toshiyuki</creatorcontrib><creatorcontrib>Shimbo, Takuro</creatorcontrib><creatorcontrib>Kobayashi, Yuka</creatorcontrib><creatorcontrib>Okamoto, Makoto</creatorcontrib><creatorcontrib>Mitsuno, Yuzo</creatorcontrib><creatorcontrib>Ogura, Keiji</creatorcontrib><creatorcontrib>Hirata, Yoshihiro</creatorcontrib><creatorcontrib>Fujimoto, Kazuma</creatorcontrib><creatorcontrib>Akiyama, Junichi</creatorcontrib><creatorcontrib>Uemura, Naomi</creatorcontrib><creatorcontrib>Koike, Kazuhiko</creatorcontrib><title>Acute Middle Gastrointestinal Bleeding Risk Associated with NSAIDs, Antithrombotic Drugs, and PPIs: A Multicenter Case-Control Study</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Middle gastrointestinal bleeding (MGIB) risk has not been fully investigated due to its extremely rare occurrence and the need for multiple endoscopies to exclude upper and lower gastrointestinal bleeding. This study investigated whether MGIB is associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin (LDA), thienopyridines, anticoagulants, and proton-pump inhibitors (PPIs), and whether PPI use affects the interactions between MGIB and antithrombotic drugs.
In this multicenter, hospital-based, case-control study, 400 patients underwent upper and lower endoscopy, 80 had acute overt MGIB and 320 had no bleeding and were matched for age and sex as controls (1:4). MGIB was additionally evaluated by capsule and/or double-balloon endoscopy, after excluding upper and lower GI bleeding. Adjusted odds ratios (AOR) for MGIB risk were calculated using conditional logistic regression. To estimate the propensity score, we employed a logistic regression model for PPI use.
In patients with MGIB, mean hemoglobin level was 9.4 g/dL, and 28 patients (35%) received blood transfusions. Factors significantly associated with MGIB were chronic kidney disease (p<0.001), liver cirrhosis (p = 0.034), NSAIDs (p<0.001), thienopyridines (p<0.001), anticoagulants (p = 0.002), and PPIs (p<0.001). After adjusting for these factors, NSAIDs (AOR, 2.5; p = 0.018), thienopyridines (AOR, 3.2; p = 0.015), anticoagulants (AOR, 4.3; p = 0.028), and PPIs (AOR; 2.0; p = 0.021) were independently associated with MGIB. After adjusting for propensity score, the use of PPIs remained an independent risk factors for MGIB (AOR, 1.94; p = 0.034). No significant interactions were observed between PPIs and NSAIDs (AOR, 0.7; p = 0.637), LDA (AOR, 0.3; p = 0.112), thienopyridine (AOR, 0.7, p = 0.671), or anticoagulants (AOR, 0.5; p = 0.545).
One-third of patients with acute small intestinal bleeding required blood transfusion. NSAIDs, thienopyridines, anticoagulants, and PPIs increased the risk of acute small intestinal bleeding. However, there were no significant interactions found between antithrombotic drugs and PPI use for bleeding risk.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Analysis</subject><subject>Anti-inflammatory agents</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - adverse effects</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - therapeutic use</subject><subject>Anticoagulants</subject><subject>Anticoagulants - adverse effects</subject><subject>Anticoagulants - therapeutic use</subject><subject>Aspirin</subject><subject>Aspirin - adverse effects</subject><subject>Aspirin - therapeutic use</subject><subject>Balloon treatment</subject><subject>Biology and Life Sciences</subject><subject>Bleeding</subject><subject>Blood</subject><subject>Blood transfusion</subject><subject>Case studies</subject><subject>Case-Control Studies</subject><subject>Cirrhosis</subject><subject>Colonoscopy</subject><subject>Departments</subject><subject>Dosage and administration</subject><subject>Drug dosages</subject><subject>Drug therapy</subject><subject>Drugs</subject><subject>Endoscopy</subject><subject>Female</subject><subject>Gastroenterology</subject><subject>Gastrointestinal Hemorrhage - chemically induced</subject><subject>Health risk assessment</subject><subject>Hemoglobin</subject><subject>Hemorrhage</subject><subject>Hepatology</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Intestinal diseases</subject><subject>Intestine</subject><subject>Liver</subject><subject>Liver cirrhosis</subject><subject>Liver diseases</subject><subject>Male</subject><subject>Medical screening</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Middle Aged</subject><subject>Nonsteroidal anti-inflammatory agents</subject><subject>Nonsteroidal anti-inflammatory drugs</subject><subject>Patients</subject><subject>Platelet Aggregation Inhibitors - adverse effects</subject><subject>Platelet Aggregation Inhibitors - therapeutic use</subject><subject>Proton pump inhibitors</subject><subject>Proton Pump Inhibitors - adverse effects</subject><subject>Proton Pump Inhibitors - therapeutic use</subject><subject>Regression models</subject><subject>Retrospective Studies</subject><subject>Risk analysis</subject><subject>Risk Factors</subject><subject>Studies</subject><subject>Thienopyridines</subject><subject>Transfusion</subject><subject>Young 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Middle Gastrointestinal Bleeding Risk Associated with NSAIDs, Antithrombotic Drugs, and PPIs: A Multicenter Case-Control Study</title><author>Nagata, Naoyoshi ; Niikura, Ryota ; Yamada, Atsuo ; Sakurai, Toshiyuki ; Shimbo, Takuro ; Kobayashi, Yuka ; Okamoto, Makoto ; Mitsuno, Yuzo ; Ogura, Keiji ; Hirata, Yoshihiro ; Fujimoto, Kazuma ; Akiyama, Junichi ; Uemura, Naomi ; Koike, Kazuhiko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-7cb84035f62a62bf5ea5a0127c2c8b2c3429097f03db17c53d8d7f0e9f0829333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Analysis</topic><topic>Anti-inflammatory agents</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - adverse effects</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - therapeutic use</topic><topic>Anticoagulants</topic><topic>Anticoagulants - 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Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nagata, Naoyoshi</au><au>Niikura, Ryota</au><au>Yamada, Atsuo</au><au>Sakurai, Toshiyuki</au><au>Shimbo, Takuro</au><au>Kobayashi, Yuka</au><au>Okamoto, Makoto</au><au>Mitsuno, Yuzo</au><au>Ogura, Keiji</au><au>Hirata, Yoshihiro</au><au>Fujimoto, Kazuma</au><au>Akiyama, Junichi</au><au>Uemura, Naomi</au><au>Koike, Kazuhiko</au><au>Grolmusz, Vince</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Acute Middle Gastrointestinal Bleeding Risk Associated with NSAIDs, Antithrombotic Drugs, and PPIs: A Multicenter Case-Control Study</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-03-15</date><risdate>2016</risdate><volume>11</volume><issue>3</issue><spage>e0151332</spage><epage>e0151332</epage><pages>e0151332-e0151332</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Middle gastrointestinal bleeding (MGIB) risk has not been fully investigated due to its extremely rare occurrence and the need for multiple endoscopies to exclude upper and lower gastrointestinal bleeding. This study investigated whether MGIB is associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin (LDA), thienopyridines, anticoagulants, and proton-pump inhibitors (PPIs), and whether PPI use affects the interactions between MGIB and antithrombotic drugs.
In this multicenter, hospital-based, case-control study, 400 patients underwent upper and lower endoscopy, 80 had acute overt MGIB and 320 had no bleeding and were matched for age and sex as controls (1:4). MGIB was additionally evaluated by capsule and/or double-balloon endoscopy, after excluding upper and lower GI bleeding. Adjusted odds ratios (AOR) for MGIB risk were calculated using conditional logistic regression. To estimate the propensity score, we employed a logistic regression model for PPI use.
In patients with MGIB, mean hemoglobin level was 9.4 g/dL, and 28 patients (35%) received blood transfusions. Factors significantly associated with MGIB were chronic kidney disease (p<0.001), liver cirrhosis (p = 0.034), NSAIDs (p<0.001), thienopyridines (p<0.001), anticoagulants (p = 0.002), and PPIs (p<0.001). After adjusting for these factors, NSAIDs (AOR, 2.5; p = 0.018), thienopyridines (AOR, 3.2; p = 0.015), anticoagulants (AOR, 4.3; p = 0.028), and PPIs (AOR; 2.0; p = 0.021) were independently associated with MGIB. After adjusting for propensity score, the use of PPIs remained an independent risk factors for MGIB (AOR, 1.94; p = 0.034). No significant interactions were observed between PPIs and NSAIDs (AOR, 0.7; p = 0.637), LDA (AOR, 0.3; p = 0.112), thienopyridine (AOR, 0.7, p = 0.671), or anticoagulants (AOR, 0.5; p = 0.545).
One-third of patients with acute small intestinal bleeding required blood transfusion. NSAIDs, thienopyridines, anticoagulants, and PPIs increased the risk of acute small intestinal bleeding. However, there were no significant interactions found between antithrombotic drugs and PPI use for bleeding risk.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26978517</pmid><doi>10.1371/journal.pone.0151332</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2016-03, Vol.11 (3), p.e0151332-e0151332 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1773468918 |
| source | MEDLINE; Public Library of Science; DOAJ Directory of Open Access Journals; PubMed Central; Free Full-Text Journals in Chemistry; EZB Electronic Journals Library |
| subjects | Adult Aged Aged, 80 and over Analysis Anti-inflammatory agents Anti-Inflammatory Agents, Non-Steroidal - adverse effects Anti-Inflammatory Agents, Non-Steroidal - therapeutic use Anticoagulants Anticoagulants - adverse effects Anticoagulants - therapeutic use Aspirin Aspirin - adverse effects Aspirin - therapeutic use Balloon treatment Biology and Life Sciences Bleeding Blood Blood transfusion Case studies Case-Control Studies Cirrhosis Colonoscopy Departments Dosage and administration Drug dosages Drug therapy Drugs Endoscopy Female Gastroenterology Gastrointestinal Hemorrhage - chemically induced Health risk assessment Hemoglobin Hemorrhage Hepatology Hospitals Humans Inflammation Intestinal diseases Intestine Liver Liver cirrhosis Liver diseases Male Medical screening Medicine Medicine and Health Sciences Middle Aged Nonsteroidal anti-inflammatory agents Nonsteroidal anti-inflammatory drugs Patients Platelet Aggregation Inhibitors - adverse effects Platelet Aggregation Inhibitors - therapeutic use Proton pump inhibitors Proton Pump Inhibitors - adverse effects Proton Pump Inhibitors - therapeutic use Regression models Retrospective Studies Risk analysis Risk Factors Studies Thienopyridines Transfusion Young Adult |
| title | Acute Middle Gastrointestinal Bleeding Risk Associated with NSAIDs, Antithrombotic Drugs, and PPIs: A Multicenter Case-Control Study |
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