{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T21:24:02Z","timestamp":1785619442199,"version":"3.56.0"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":4475,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,6]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Nonselective \u03b2\u2013blockers are very effective in preventing first variceal bleeding in patients with cirrhosis. Treatment with isosorbide\u20135\u2013mononitrate (IS\u2013MN) plus propranolol achieves a greater reduction in portal pressure than propranolol alone. The present multicenter, prospective, double\u2013blind, randomized, controlled trial evaluated whether combined drug therapy could be more effective than propranolol alone in preventing variceal bleeding. A total of 349 consecutive cirrhotic patients with gastroesophageal varices were randomized to receive propranolol + placebo (n = 174) or propranolol + IS\u2013MN (n = 175). There were no significant differences in the 1\u2013 and 2\u2013year actuarial probability of variceal bleeding between the 2 groups (propranolol + placebo, 8.3% and 10.6%; propranolol + IS\u2013MN, 5% and 12.5%). The only independent predictor of variceal bleeding was a variceal size greater than 5 mm. However, among patients with varices greater than 5 mm (n = 196), there were no significant differences in the incidence of variceal bleeding between the 2 groups. Survival was also similar. Adverse effects were significantly more frequent in the propranolol + IS\u2013MN group due to a greater incidence of headache. There were no significant differences in the incidence of new\u2013onset or worsening ascites or in impairment of renal function. In conclusion, propranolol effectively prevents variceal bleeding. Adding IS\u2013MN does not further decrease the low residual risk of bleeding in patients receiving propranolol. However, the long\u2013term use of this combination drug therapy is safe and may be an alternative in clinical conditions associated with a greater risk of bleeding.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1053\/jhep.2003.50211","type":"journal-article","created":{"date-parts":[[2003,5,28]],"date-time":"2003-05-28T22:17:49Z","timestamp":1054160269000},"page":"1260-1266","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":135,"title":["Propranolol Plus Placebo Versus Propranolol Plus Isosorbide\u20135\u2013Mononitrate in the Prevention of A First Variceal Bleed: A Double\u2013Blind Rct"],"prefix":"10.1097","volume":"37","author":[{"given":"Juan 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