{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T16:42:55Z","timestamp":1777308175794,"version":"3.51.4"},"reference-count":33,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,2,19]],"date-time":"2014-02-19T00:00:00Z","timestamp":1392768000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aim<\/jats:title><jats:p>The effect of combined therapies (among non\u2010selected beta\u2010blockers [<jats:styled-content style=\"fixed-case\">NSBB<\/jats:styled-content>], endoscopic therapy, and other treatments) on the first variceal bleeding has been evaluated in several randomized controlled trials previously, and the results were controversial. We performed this meta\u2010analysis to assess the effect of combined therapies in patients with high\u2010risk varices without previous variceal bleeding.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>ochrane <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>ibrary, The <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>ochrane <jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>epato\u2010<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>iliary <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>roup <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>ontrolled <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>rials <jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>egister, <jats:styled-content style=\"fixed-case\">MEDLINE<\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\">EMBASE<\/jats:styled-content> were searched for eligible trials. Manual searches were also performed for additional studies. Upper gastrointestinal bleeding, variceal bleeding, mortality, and adverse events were evaluated as end\u2010points by meta\u2010analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twelve randomized controlled trials with 1571 patients were included. Compared with the <jats:styled-content style=\"fixed-case\">NSBB<\/jats:styled-content> (propranolol or nadolol) or endoscopic therapy alone, all of the combined therapies did not demonstrate significant improvements in variceal bleeding, total upper gastrointestinal bleeding, and mortality. Only the combinations of isosorbide\u2010mononitrate or spironolactone with <jats:styled-content style=\"fixed-case\">NSBB<\/jats:styled-content> tended to decrease the risk of variceal bleeding when compared with the use of <jats:styled-content style=\"fixed-case\">NSBB<\/jats:styled-content> alone (isosorbide\u2010mononitrate plus <jats:styled-content style=\"fixed-case\">NSBB<\/jats:styled-content>\u2005<jats:italic>vs<\/jats:italic>\u2005<jats:styled-content style=\"fixed-case\">NSBB<\/jats:styled-content>: odds ratio\u2009=\u20090.67, 95% confidence interval 0.40\u20131.13, <jats:italic>P<\/jats:italic>\u2009=\u20090.13; spironolactone plus <jats:styled-content style=\"fixed-case\">NSBB<\/jats:styled-content>\u2005<jats:italic>vs<\/jats:italic>\u2005<jats:styled-content style=\"fixed-case\">NSBB<\/jats:styled-content>: odds ratio\u2009=\u20090.41, 95% confidence interval 0.10\u20131.69, <jats:italic>P<\/jats:italic>\u2009=\u20090.22). Adverse events were more frequently observed in the combined therapy groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Based on the available evidences, no combined therapy can be recommended as the first\u2010line treatment for the primary prevention of variceal bleeding currently. Further studies with large sample sizes and long\u2010term follow up are warranted.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.12396","type":"journal-article","created":{"date-parts":[[2013,10,12]],"date-time":"2013-10-12T02:40:40Z","timestamp":1381545640000},"page":"442-452","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Combined therapies versus monotherapies for the first variceal bleeding in patients with high\u2010risk varices: A meta\u2010analysis of randomized controlled trials"],"prefix":"10.1111","volume":"29","author":[{"given":"Ming","family":"Bai","sequence":"first","affiliation":[{"name":"Xijing Hospital of Digestive Diseases Fourth Military Medical University  Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingshun","family":"Qi","sequence":"additional","affiliation":[{"name":"Xijing Hospital of Digestive Diseases Fourth Military Medical University  Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Man","family":"Yang","sequence":"additional","affiliation":[{"name":"Xijing Hospital of Digestive Diseases Fourth Military Medical University  Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guohong","family":"Han","sequence":"additional","affiliation":[{"name":"Xijing Hospital of Digestive Diseases Fourth Military Medical University  Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daiming","family":"Fan","sequence":"additional","affiliation":[{"name":"Xijing Hospital of Digestive Diseases Fourth Military Medical University  Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,2,19]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21907"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(02)00420-8"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198810133191505"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa044456"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.49.5.682"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20339"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0901512"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-117-1-59"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.23054"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2007.01564.x"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2005.02346.x"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.10.028"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8278(90)90112-5"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.27993"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510300124"},{"key":"e_1_2_5_17_1","first-page":"145","article-title":"Hemodynamic effect of spironolactone in liver cirrhosis and propranolol\u2010resistant portal hypertension","volume":"21","author":"Sen S","year":"2002","journal-title":"Indian J. 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