{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:09:54Z","timestamp":1790507394444,"version":"4.1.0"},"reference-count":69,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,4,15]],"date-time":"2016-04-15T00:00:00Z","timestamp":1460678400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:p>Particular concerns have been raised regarding the association between non\u2010vitamin K antagonist oral anticoagulants (NOACs) and the risk of gastrointestinal bleeding (GIB); however, current findings are still inconclusive. We conducted a systematic review with a meta\u2010analysis to examine the association between NOACs and GIB in real\u2010life settings. We performed a systematic search of PubMed, EMBASE and CINAHL Plus up to September 2015. Observational studies that evaluated exposure to NOACs reporting GIB outcomes were included. The inverse variance method using the random\u2010effects model was used to calculate the pooled estimates. Eight cohort studies were included in the primary meta\u2010analysis, enrolling 1442 GIB cases among 106\u00a0626 dabigatran users (49\u00a0486 patient\u2010years), and 184 GIB cases among 10\u00a0713 rivaroxaban users (4046 patient\u2010years). The pooled incidence rates of GIB were 4.50 [95% confidence interval (CI) 3.17, 5.84] and 7.18 (95% CI 2.42, 12.0) per 100 patient\u2010years among dabigatran and rivaroxaban users, respectively. The summary risk ratio (RR) was 1.21 (95% CI 1.05, 1.39) for dabigatran compared with warfarin, and 1.09 (95% CI 0.92, 1.30) for rivaroxaban. Subgroup analyses showed a dose\u2010related effect of dabigatran, with a significantly higher risk of GIB for 150\u00a0mg b.i.d. (RR\u00a0=\u00a01.51, 95% CI 1.34, 1.70) but not for 75\u00a0mg b.i.d. or 110\u00a0mg b.i.d.. In addition, the use of proton pump inhibitors (PPIs)\/histamine H2\u2010receptor antagonists (H2RAs) influenced the association in dabigatran users, whereas this effect was modest among rivaroxaban users. In conclusion, our meta\u2010analysis suggested a slightly higher risk of GIB with dabigatran use compared with warfarin, whereas no significant difference was found between rivaroxaban and warfarin for GIB risk.<\/jats:p>","DOI":"10.1111\/bcp.12911","type":"journal-article","created":{"date-parts":[[2016,2,18]],"date-time":"2016-02-18T14:38:00Z","timestamp":1455806280000},"page":"285-300","source":"Crossref","is-referenced-by-count":39,"title":["The association between non\u2010vitamin K antagonist oral anticoagulants and gastrointestinal bleeding: a meta\u2010analysis of observational studies"],"prefix":"10.1111","volume":"82","author":[{"given":"Ying","family":"He","sequence":"first","affiliation":[{"name":"Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy The University of Hong Kong  Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian C. K.","family":"Wong","sequence":"additional","affiliation":[{"name":"Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy The University of Hong Kong  Hong Kong"},{"name":"Research Department of Practice and Policy, School of Pharmacy University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Li","sequence":"additional","affiliation":[{"name":"Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy The University of Hong Kong  Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shweta","family":"Anand","sequence":"additional","affiliation":[{"name":"Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy The University of Hong Kong  Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai K.","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Medicine, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung Wah","family":"Siu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther W.","family":"Chan","sequence":"additional","affiliation":[{"name":"Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy The University of Hong Kong  Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,4,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.010426"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0905561"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1009638"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1107039"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1310907"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1007903"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1113572"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0906598"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.11-2292"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2014.08.001"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht134"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1752-1947-6-129"},{"key":"e_1_2_8_14_1","first-page":"388","article-title":"Dabigatran etexilate linked to fatal gastrointestinal hemorrhage","volume":"16","author":"Feinberg J","year":"2014","journal-title":"Isr Med Assoc J"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3109\/15563650.2012.705290"},{"key":"e_1_2_8_16_1","first-page":"e325","article-title":"Adherence, persistence, and switching patterns of dabigatran etexilate","volume":"19","author":"Tsai K","year":"2013","journal-title":"Am J Manag Care"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.02.041"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-07-590323"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-14-1042"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2015.04.004"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)62343-0"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2015.01.159"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2013.11.049"},{"key":"e_1_2_8_24_1","unstructured":"The U.S. Food and Drug Administration (FDA).FDA Drug Safety Communication: Update on the risk for serious bleeding events with the anticoagulant Pradaxa (dabigatran).2012[online]. 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