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Propranolol prevents first gastrointestinal bleeding in non-ascitic cirrhotic patients

Final report of a multicenter randomized trial
  • Affiliations
    Divisione di Medicina, Istituto di Medicina Generale e Pneumologia, Ospedale V. Cervello, Palermo, Italy

    Istituto di Gastroenterologia, Università di Modena, Modena, Italy

    Divisione di Gastroenterologia, Ospedale Generale Regionale, Bolzano, Italy

    Divisione di Medicina, Instituti Ospedalieri S. Corona, Pietra Ligure, Italy

    Istituto di Biometria, Università di Milano, Milano, Italy
  • Author Footnotes
    ∗ The following participated in the Italian Multizenter Project for Propranolol in Bleeding: Planning committee. Luigi Pagliaro, Professor of Medicine, Gennaro D'Amico MD, Linda Pasta MD, M. Gabriella Filippazzo MD, Federico Manenti, Professor of Gastroenterology, Giorgio Dobrilla MD and Giorgio Marenco MD. Steering committee: Linda Pasta MD, Gennaro D'Amico MD, Salvatore Le Moli MD, Alberto Ferrari MD, Giovanni De Pretis MD, Federico Oberhollenzer MD and Giorgio Marenco MD. Writing committee: Gennaro D'Amico MD. Luigi Pagliaro, Professor of Medicine and Linda Pasta MD. Other participants: Mariano Amuso MD, Sonia Di Piazza MD, Giovanna Gatto MD, Ga. dolfo Giannuoli MD, Alberto Maringhini MD, Ugo Palazzo MD, Giovambattista Pinzello MD, R Giovanna Simonetti MD, Maria Caltagirone MD, Silvio Magrin MD, M. Pia Marceno' MD, Mario Traina MD, Miriam Turri MD, Maria Vinci MD, Roberto Virdone MD, Giovanni Vizzini MD, Mario Cottone MD, Elio Sciarrino MD, Alberto Merighi MD, Giampiero Rigo MD, Lucia Piazzi MD, Maurizio Valentini MD, Harald Steiner MD, Antonio Giudici Cipriani MD, Gianluigi Dante MD and Giorgio Menardo MD. Statistical analysis: Alberto Morabito, Professor of Biomathematics, Gennaro D'Amico MD and Fabio Tine MD.
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      Abstract

      We report here the final analysis of a multicentre randomized, single-blind trial of propranolol for prophylaxis of first bleeding in cirrhosis. One hundred and seventy-four consecutive patients with large esophageal varices were randomly assigned to either propranolol in doses reducing the resting heart rate by 25% (85 patients) or to a placebo (vitamin K: 89 patients). Three were lost to follow-up and 26 had to be withdrawn from propranolol because of side effects (n = 23) or low compliance (n = 3). The cumulative value over 42 months of patients free of bleeding was 74% (95% confidence interval = 85%-63%) in the propranolol and 59% (95% CI = 79%-43%) in the control group and the corresponding survival figures were 51% (95% CI = 63%-39%) and 59% (95% CI = 75%-43%): neither of the differences was significant. A retrospective analysis according to the presence of ascites at randomization showed that In the subset without ascites the proportion of patients free of bleeding was significantly higher in the propranolol group than in the control group (83% vs. 61%: 95% CI = 97%-69% and 78%-44%, respectively; P = 0.028); this difference was even more evident in the ascites-free period (94% vs. 58%; 95% CI = 100%-86% and 76%-40%, respectively; P = 0,002). No differences were found in patients with ascites at randomization. Survival was not significantly affected by treatment in any subgroup, although it was shorter in the ascitic patients given propranolol than in controls (33% vs. 49%; 95% CI = 51%-15% and 71%-27%, respectively; P = 0.07) Our conclusion was that propranolol prevents first bleeding in cirrhotic patients with large varices and without ascites. Further studies are needed to assess its effectiveness and safely in ascitic patients.
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