title: Carvedilol for primary prophylaxis of variceal bleeding in cirrhotic patients with haemodynamic non-response to propranolol.
abstract: OBJECTIVE
  Non-selective β-blockers or endoscopic band ligation (EBL) are recommended for primary prophylaxis of variceal bleeding in patients with oesophageal varices. Additional α-adrenergic blockade (as by carvedilol) may increase the number of patients with haemodynamic response (reduction in hepatic venous pressure gradient (HVPG) of ≥ 20% or to values <12 mm Hg).
  
  
  METHODS
  Patients with oesophageal varices undergoing measurement of HVPG before and under propranolol treatment (80-160 mg/day) were included. HVPG responders were kept on propranolol (PROP group), while non-responders were placed on carvedilol (6.25-50 mg/day). Carvedilol responders continued treatment (CARV group), while non-responders to carvedilol underwent EBL. The primary aim was to assess haemodynamic response rates to carvedilol in propranolol non-responders.
  
  
  RESULTS
  36% (37/104) of patients showed a HVPG response to propranolol. Among the propranolol non-responders 56% (38/67) eventually achieved a haemodynamic response with carvedilol, while 44% (29/67) patients were finally treated with EBL. The decrease in HVPG was significantly greater with carvedilol (median 12.5 mg/day) than with propranolol (median 100 mg/day): -19 ± 10% versus -12 ± 11% (p<0.001). During a 2 year follow-up bleeding rates for PROP were 11% versus CARV 5% versus EBL 25% (p=0.0429). Fewer episodes of hepatic decompensation (PROP 38%/CARV 26% vs EBL 55%; p=0.0789) and significantly lower mortality (PROP 14%/CARV 11% vs EBL 31%; p=0.0455) were observed in haemodynamic responders compared to the EBL group.
  
  
  CONCLUSIONS
  Carvedilol leads to a significantly greater decrease in HVPG than propranolol. Using carvedilol for primary prophylaxis a substantial proportion of non-responders to propranolol can achieve a haemodynamic response, which is associated with improved outcome with regard to prevention of variceal bleeding, hepatic decompensation and death.
authors.affiliation: Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, , Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Reiberger
authors.forename: Gregor
authors.initials: G
authors.lastname: Ulbrich
authors.forename: Arnulf
authors.initials: A
authors.lastname: Ferlitsch
authors.forename: Berit Anna
authors.initials: BA
authors.lastname: Payer
authors.forename: Philipp
authors.initials: P
authors.lastname: Schwabl
authors.forename: Matthias
authors.initials: M
authors.lastname: Pinter
authors.forename: Birgit B
authors.initials: BB
authors.lastname: Heinisch
authors.forename: Michael
authors.initials: M
authors.lastname: Trauner
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kramer
authors.forename: Markus
authors.initials: M
authors.lastname: Peck-Radosavljevic
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D002227:Carbazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D000077261:Carvedilol; D004305:Dose-Response Relationship, Drug; D004932:Esophageal and Gastric Varices / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D006471:Gastrointestinal Hemorrhage / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D008026:Ligation; D008103:Liver Cirrhosis / Q000150:complications* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000008:administration & dosage / Q000627:therapeutic use*; D011433:Propranolol / Q000627:therapeutic use; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D011433:Propranolol