Nadolol plus isosorbide mononitrate alone or associated with band ligation in the prevention of recurrent bleeding: a multicentre randomised controlled trial
- J C García-Pagán1,2,
- C Villanueva2,3,
- A Albillos2,4,
- R Bañares2,5,
- R Morillas2,6,
- J G Abraldes1,2,
- J Bosch1,2
- 1Hepatic Hemodynamic Laboratory, Liver Unit, Institut de Malalties Digestives i Metaboliques, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
- 2Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Barcelona, Madrid, Spain
- 3Department of Gastroenterology, Hospital Sant Pau, Barcelona, Spain
- 4Department of Gastroenterology, Hospital Universitario Ramón y Cajal, University of Alcalá, Madrid, Spain
- 5Department of Gastroenterology, Hospital General Universitario Gregorio Marañón, Madrid, Spain
- 6Department of Gastroenterology, Hospital Universitari Germans Trias y Pujol, Badalona, Spain
- Dr J Bosch, Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic, C Villaroel, 170, Barcelona 08036, Spain;
- Revised 15 December 2008
- Accepted 20 January 2009
- Published Online First 12 February 2009
Background and aims: Previous clinical trials suggest that adding non-selective beta-blockers improves the efficacy of endoscopic band ligation (EBL) in the prevention of recurrent bleeding, but no study has evaluated whether EBL improves the efficacy of beta-blockers + isosorbide-5-mononitrate. The present study was aimed at evaluating this issue in a multicentre randomised controlled trial (RCT) and to correlate changes in hepatic venous pressure gradient (HVPG) during treatment with clinical outcomes
Methods: 158 patients with cirrhosis, admitted because of variceal bleeding, were randomised to receive nadolol+isosorbide-5-mononitrate alone (Drug: n = 78) or combined with EBL (Drug+EBL; n = 80). HVPG measurements were performed at randomisation and after 4–6 weeks on medical therapy.
Results: Median follow-up was 15 months. One-year probability of recurrent bleeding was similar in both groups (33% vs 26%: p = 0.3). There were no significant differences in survival or need of rescue shunts. Overall adverse events or those requiring hospital admission were significantly more frequent in the Drug+EBL group. Recurrent bleeding was significantly more frequent in HVPG non-responders than in responders (HVPG reduction ⩾20% or ⩽12 mm Hg). Among non-responders recurrent bleeding was similar in patients treated with Drugs or Drugs+EBL.
Conclusions: Adding EBL to pharmacological treatment did not reduce recurrent bleeding, the need for rescue therapy, or mortality, and was associated with more adverse events. Furthermore, associating EBL to drug therapy did not reduce the high rebleeding risk of HVPG non-responders.
Competing interests: None.
Funding: Supported in part by grants from Instituto de Salud Carlos III (FIS 04/0655 and 06/0623). Ciberehd is funded by Instituto de Salud Carlos III. Nadolol was kindly supplied by Sanofi Winthrop (Barcelona, Spain). Isosorbide mononitrate was kindly provided by Lacer (Barcelona, Spain).
Ethics approval: The study protocol was approved by the Ethics Committees of all participating hospitals and by the Ministry of Health, and fulfilled the guidelines of Good Clinical Practice in clinical trials.
See Commentary, p 1046