{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T06:19:37Z","timestamp":1792995577506,"version":"4.5.0"},"reference-count":60,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T00:00:00Z","timestamp":1757203200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>Nonsteroidal anti\u2010inflammatory drugs (NSAIDs) are widely used for pain and inflammation but are associated with gastrointestinal (GI) bleeding. While this risk is well established, most studies evaluate NSAIDs as a homogenous class, limiting clinical decision\u2010making based on individual agent safety. This systematic review and meta\u2010analysis aimed to quantify the risk of GI bleeding associated with individual NSAIDs. We searched PubMed from inception through January 2025 using MeSH and free\u2010text terms for \u201cgastrointestinal bleeding\u201d and nine commonly used NSAIDs. A random effects meta\u2010analysis was conducted to estimate the pooled odds ratios (ORs) for GI bleeding, with hazard ratios (HRs) and relative risks (RRs) treated as approximations of ORs due to the rare event nature of GI bleeding. Of 6,711 records screened, 25 studies met the inclusion criteria. Substantial heterogeneity in study design, populations, and outcome ascertainment was observed. Celecoxib was associated with the lowest risk of GI bleeding (OR 1.16, 95% CI: 0.84\u20131.61). Among non\u2010selective NSAIDs, ibuprofen had the lowest significant risk (OR 2.28, 95% CI: 1.71\u20133.03), while ketorolac showed the highest risk (OR 20.67, 95% CI: 14.56\u201329.34). Other agents, such as piroxicam and meloxicam, also demonstrated significantly elevated risks. The risk of GI bleeding varies widely among individual NSAIDs. Celecoxib appears to have the lowest GI risk, though cardiovascular safety must also be considered. These findings highlight the need for personalized NSAID selection and suggest that NSAIDs should not be treated as a uniform class when assessing bleeding risk.<\/jats:p>","DOI":"10.1002\/cpt.70054","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:17:51Z","timestamp":1757290671000},"page":"46-62","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Nonsteroidal Anti\u2010Inflammatory Drugs and Risk of Gastrointestinal Bleeding: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1002","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4939-9353","authenticated-orcid":false,"given":"Abdelrahman G.","family":"Tawfik","sequence":"first","affiliation":[{"name":"Department of Pharmacotherapy College of Pharmacy, University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3916-0402","authenticated-orcid":false,"given":"Ainhoa","family":"Gomez\u2010Lumbreras","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy College of Pharmacy, University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9954-6799","authenticated-orcid":false,"given":"Guilherme","family":"Del Fiol","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, School of Medicine University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4282-9338","authenticated-orcid":false,"given":"Kensaku","family":"Kawamoto","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, School of Medicine University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2041-7404","authenticated-orcid":false,"given":"Katy E.","family":"Trinkley","sequence":"additional","affiliation":[{"name":"School of Medicine University of Colorado Anschutz Medical Campus  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1081-1670","authenticated-orcid":false,"given":"Thomas","family":"Reese","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aubrey","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy College of Pharmacy, University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5006-9394","authenticated-orcid":false,"given":"Daniel C.","family":"Malone","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy College of Pharmacy, University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,7]]},"reference":[{"key":"e_1_2_11_1_1","doi-asserted-by":"publisher","DOI":"10.1177\/1744806918770320"},{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11739-019-02266-2"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.5402\/2011\/480291"},{"key":"e_1_2_11_4_1","first-page":"3","article-title":"Mechanism of action of antiinflammatory drugs","volume":"20","author":"Vane J.R.","year":"1998","journal-title":"Int. J. Tissue React."},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/pme.12282"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2023.06.008"},{"key":"e_1_2_11_7_1","volume-title":"Share of adults with chronic low back pain who used over\u2010the\u2010counter NSAIDs for pain management in the United States, by age","author":"Statista","year":"2022"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.10.049"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2012.04.002"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-18654-2"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27412"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2014.82"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0040-1710592"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03261999"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.160.14.2093"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_11_17_1","first-page":"1","volume-title":"The Newcastle\u2010Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta\u2010Analyses","author":"Peterson J.","year":"2011"},{"key":"e_1_2_11_18_1","first-page":"89","article-title":"Anti\u2010rheumatic and analgesic drug usage and acute gastro\u2010intestinal bleeding in elderly patients","volume":"10","author":"Alexander A.M.","year":"1985","journal-title":"J. Clin. Hosp. Pharm."},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajem.2019.06.009"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.165.2.189"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60900-9"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-012-1386-3"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)91843-0"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.158.1.33"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001648-200109000-00018"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001648-199701000-00003"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/00042737-200302000-00011"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2005.080754"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2014.11.007"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-200427060-00005"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.2002.01636.x"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.325.7365.624"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.2630010204"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2004.01913.x"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kel428"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-006-0171-6"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780360114"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(86)92927-2"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/00365520701478758"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.11468"},{"key":"e_1_2_11_41_1","first-page":"1443","article-title":"Upper gastrointestinal bleeding associated with analgesics and NSAID use: a case\u2010control study","volume":"20","author":"Begaud B.","year":"1993","journal-title":"J. Rheumatol."},{"key":"e_1_2_11_42_1","first-page":"137","article-title":"Over the counter non\u2010steroidal anti\u2010inflammatory drugs and risk of gastrointestinal bleeding","volume":"5","author":"Blot W.J.","year":"2000","journal-title":"J. Epidemiol. Biostat."},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1517\/14740338.2013.780595"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.15547"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2019.10.013"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gie.2022.07.012"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2023.101871"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/463767"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-012-0717-6"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1302"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4177"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15491"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S465058"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.947285"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/ptj\/pzaa182"},{"key":"e_1_2_11_56_1","article-title":"Topical NSAIDs for chronic musculoskeletal pain in adults","volume":"4","author":"Derry S.","year":"2016","journal-title":"Cochrane Database Syst. Rev."},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-8-73"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2023.10.011"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dys147"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)66379-9"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70054","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T10:37:07Z","timestamp":1767004627000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.70054"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,7]]},"references-count":60,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/cpt.70054"],"URL":"https:\/\/doi.org\/10.1002\/cpt.70054","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,7]]},"assertion":[{"value":"2025-04-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}