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Propranolol for prophylaxis of bleeding in cirrhotic patients with large varices: A multicenter, randomized clinical trial


  • Members of the Italian Multicenter Project for Propranolol in Bleeding are: Planning committee—Luigi Pagliaro, Gennaro D'Amico, Linda Pasta, Maria Gabriella Filippazzo, Federico Manenti, Giorgio Dobrilla and Giorgio Marenco. Steering committee—Linda Pasta, Gennaro D'Amico, Maria Gabriella Filippazzo, Salvatore Le Moli, Alberto Ferrari, Giovanni De Pretis, Federico Oberhollenzer and Giorgio Marenco. Writing committee—Gennaro D'Amico, Luigi Pagliaro and Linda Pasta. Other participants—Mariano Amuso, Sonia Di Piazza, Giovanni Gatto, Gandolfo Giannuoli, Alberto Maringhini, Ugo Palazzo, Palazzo, Giov-ambattista Pinzello, R. Giovanna Simonetti, Maria Caltagirone, Silvio Magrin, M. Pia Marcenö, Mario Traina, Miriam Turri, Maria Vinci. Roberto Virdone, Giovanni Vizzini, Mario Cottone, Elio Sciarrino, Alberto Merighi, Giampiero Rigo, Lucia Piazzi, Maurizio Valentini, Harald Steiner, Antonio Giudici Cipriani, Gianluigi Dante and Giorgio Menardo. Statistical analysis—Alberto Morabito, Fabio Tinè and Gennaro D'Amico.

  • Linda Pasta, M.D., Divisione di Medicina, Istituto di Medicina Generale e Pneumologia, Ospedale “V. Cervello,” Via Trabucco 180, 90146 Palermo (Italy)

Abstract

To assess if propranolol prevents the first bleeding in cirrhosis, we randomly assigned 174 patients with large varices to either propranolol in doses reducing the resting heart rate by 25% (85 patients) or to a placebo (oral vitamin K, 89 patients). Sixty-nine patients had alcoholic cirrhosis, 24 posthepatitic cirrhosis and 81 cryp-togenic cirrhosis. At the time of inclusion, 75 patients (43%) had ascites and according to the Child-Pugh classification, 103 (59%) had Class A disease, 60 (34%) Class B and 11 (7%) Class C. We report here an interim analysis of the study when all patients had been followed for at least 1 year (mean follow-up = 22 months). At this time, the cumulative proportion of patients free of bleeding was 74% in the propranolol group and 63% in the placebo group; corresponding survival figures were 59 and 74% (both differences not significant), respectively. A retrospective analysis showed that the cumulative percentage of patients free of bleeding was significantly higher in the propranolol- than in the control-group in the subsets of patients without ascites or in Child-Pugh Class A: respectively, 87 vs. 64% (p = 0.023) and 88 vs. 64% (p = 0.01). No differences in bleeding incidence were found in patients with ascites or in Child-Pugh Class B or C. Propranolol treatment did not affect survival in any subgroup. Twenty-five patients had to be withdrawn from propranolol because of side effects (n = 23) or low compliance (n = 2). If confirmed on a longer follow-up, these results suggest that propranolol could prevent the first bleeding in patients with well-compensated cirrhosis.

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