Primary prophylaxis with nonselective β-blockers in high-risk subjects has been shown to be effective in reducing both esophageal variceal bleeding and mortality. Recently it has been suggested that band ligation may be a better option for primary prophylaxis. We compared nonselective β-blockers with band ligation in patients with large varices (F2, F3) and elevated hepatic venous wedge pressure gradient (HVWPG, ≥12 mm Hg). All patients were prospectively followed for variceal bleeding, mortality, and treatment-related complications. Based on previous published studies, we estimated that 90 patients in each arm would be required to show a difference in bleeding rate. The study was prematurely terminated when we realized that our estimated sample size was inadequate to show a difference based on the observed bleeding rate. At the time of termination, 31 patients (Child A, 11; B, 14; C, 6), with a mean HVWPG of 19 ± 9.1 mm Hg, were randomized to either band ligation (group A; n = 16) or β-blockers (group B; n = 15). Baseline demographics of both groups were similar and the mean follow-up period was 27.4 ± 12.9 months. During the follow-up, two patients in group A and one patient in group B had bleeding. Nine patients (29%; group A, six; group B, three; P = ns) died due to non-bleeding-related causes and five (16%) patients (group A, three; group B, two) underwent liver transplantation. Treatment-related complication were minimal in both groups. Despite the selection of high-risk patients, the observed bleeding rate was much lower than anticipated. Based on our observed bleeding rates, 424 patients would be required in each arm to show a difference between band ligation and β-blocker therapy.
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Merigan TC, Plotkin GR, Davidson CS: Effect of intravenously administered posterior pituitary extract on hemorrhage from bleeding esophageal varices. N Engl J Med 266:134–135, 1962
Conn HO, Ramsby GR, Storer EH, et al.: Intraarterial vasopressin in the treatment of upper gastrointestinal hemorrhage: a prospective, controlled clinical trial. Gastroenterology 68:211–221, 1975
Imperiale TF, Carlos Teran J, McCullough AJ: A meta-analysis of somatostatin versus vasopressin in the management of acute esophageal variceal hemorrhage. Gastroenterology 109:1289–1294, 1995
D’Amico G, Pietrosi G, Tarantino I, Pagliaro L: Emergency sclerotherapy versus vasoactive drugs for variceal bleeding in cirrhosis: A Cochrane meta-analysis. Gastroenterology 124:127–191, 2003
Thuluvath PH, Krishnan A: Primary prophylaxis of variceal bleeding. Gastrointest Endosc 58:558–567, 2003
Groszmann RJ, Bosch J, Grace ND, et al.: Hemodynamic events in a prospective randomized trial of propranolol versus placebo in the prevention of a first variceal hemorrhage. Gastroenterology 99:1401–1407, 1990
Beppu K, Inokuchi K, Koyanagi N, Nakayama S, Sakata H, Kitano S, Kobayashi M: Prediction of variceal hemorrhage by esophageal endoscopy. Gastrointest Endosc 27:213–218, 1981
D’Amico G, Pagliaro L, Bosch J: The treatment of portal hypertension: A meta-analytic review. Hepatology 22:332–354, 1995
Pascal JP, Cales P: Propranolol in the prevention of first upper gastrointestinal tract hemorrhage in patients with cirrhosis of the liver and esophageal varices. N Engl J Med 317:856–861, 1987
Poynard T, Cales P, Pasta L, Ideo G, Pascal JP, Pagliaro L, Lebrec D: Beta-adrenergic-antagonist drugs in the prevention of gastrointestinal bleeding in patients with cirrhosis and esophageal varices. An analysis of data and prognostic factors in 589 patients from four randomized clinical trials. Franco-Italian Multicenter Study Group. N Engl J Med 324:1532–1538, 1991
Hayes PC, Davis JM, Lewis JA, Bouchier IA: Meta-analysis of value of propranolol in prevention of variceal haemorrhage. Lancet 336:153–156, 1990
Sarin SK, Lamba GS, Kumar M, Misra A, Murthy NS: Comparison of endoscopic ligation and propranolol for the primary prevention of variceal bleeding. N Engl J Med 340:988–993, 1999
Lui HF, Stanley AJ, Forrest EH, et al.: Primary prophylaxis of variceal hemorrhage: A randomized controlled trial comparing band ligation, propranolol, and isosorbide mononitrate. Gastroenterology 123:735–744, 2002
De BK, Ghoshal UC, Das T, Santra A, Biswas PK: Endoscopic variceal ligation for primary prophylaxis of esophageal variceal bleed: Preliminary report of a randomized controlled trial. J Gastroenterol Hepatol 14:220–224, 1999
Merkel C, Sacerdoti D, Bolognesi M, et al.: Hemodynamic evaluation of the addition of isosorbide-5-mononitrate to nadolol in cirrhotic patients with insufficient response to the beta-blocker alone. Hepatology 26:34–39, 1997
Hicken BL, Sharara AI, Abrams GA, Eloubeidi M, Fallon MB, Arguedas MR: Hepatic venous pressure gradient measurements to assess response to primary prophylaxis in patients with cirrhosis: a decision analytical study. Aliment Pharmacol Ther 17:145–153, 2003
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Thuluvath, P.J., Maheshwari, A., Jagannath, S. et al. A Randomized Controlled Trial of β-Blockers Versus Endoscopic Band Ligation for Primary Prophylaxis: A Large Sample Size is Required to Show a Difference in Bleeding Rates. Dig Dis Sci 50, 407–410 (2005). https://doi.org/10.1007/s10620-005-1619-8
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DOI: https://doi.org/10.1007/s10620-005-1619-8