Randomised controlled trials (RCTs) that assessed the effects of isosorbide mononitrate for patients with oesophageal varices and either no previous bleeding (primary prevention) or previous variceal bleeding (secondary prevention) were eligible for inclusion in the review. Eligible treatment comparisons were isosorbide mononitrate alone or with beta-blockers versus placebo, no intervention, beta-blockers, endoscopic therapy (banding ligation or sclerotherapy), transjugular intrahepatic portosystemic shunts (TIPS) or a combination of isosorbide mononitrate plus beta-blockers and endoscopic therapy. Studies had to report mortality (primary outcome). Secondary outcomes included upper gastrointestinal bleeding, variceal bleeding, bleeding-related mortality and adverse events.
Most of the included studies assessed secondary prevention and others assessed primary prevention. Some primary prevention trials compared isosorbide mononitrate against placebo, beta-blockers or banding ligation; others compared isosorbide mononitrate plus beta-blockers against beta-blockers or banding ligation. Secondary prevention trials compared isosorbide mononitrate plus beta-blockers alone or with banding ligation versus beta-blockers, endoscopic therapy or TIPS. Initial doses of isosorbide mononitrate ranged from 20 to 40mg/day to a maximum of 40 to 80mg/day. Mean dose ranged from 30 to 73mg/day. Beta-blockers assessed included nadolol and propranolol. Initial doses ranged from 40 to 80mg/day. In most trials, dose was adjusted to achieve a resting heart rate of about 55 to 60 beats per minute, 20% to 25% reduction in resting heart rate or a maximum of 160 to 240mg/day if tolerated. Mean dose of beta-blockers ranged from 40 to 125mg/day.
Reported exclusion criteria for participants included contraindications to isosorbide mononitrate or beta-blockers (heart disease with aortic stenosis or atrioventricular block, peripheral ischaemic disease or chronic pulmonary disease), chronic renal failure and malignant disease. In trials on isosorbide mononitrate and beta-blockers, isosorbide mononitrate was initiated after the maintenance dose of beta-blocker was achieved. Patients with cirrhosis comprised 85% to 100% of patients. The proportion of patients with large varices ranged from 36% to 100% in trials on primary prevention and from 77% to 100% in trials on secondary prevention. The mean age of included patients ranged from 51 to 66 years. The proportion of men ranged from 53% to 85%. Trials were performed in Argentina, China, Egypt, France, UK, India, Italy, Pakistan, Spain and Taiwan. Maximum duration of follow-up ranged from eight to 91 months (median 24 months).
Two reviewers assessed the studies for inclusion.