Poster Presentations

Session Title: Category 2b. CIRRHOSIS AND ITS COMPLICATIONS: b. CLINICAL ASPECTS
Presentation Date: Apr 15, 2010

CARVEDILOL OR PROPRANOLOL IN PORTAL HYPERTENSION? A RANDOMIZED CLINICAL TRIAL

L. Hobolth¹*, S. Møller², H. Grønbæk³, S. Keiding⁴, F. Bendtsen¹, E. Feldager^1
1Department of Gastroenterology, ²Department of Clinical Physiology and Nuclear Medicine, Hvidovre University Hospital, Hvidovre, ³Department of Medicine, ⁴PET Center, Aarhus University Hospital, Aarhus, Denmark. *lise@hobolth.dk

Background: Propranolol is used in primary and secondary prevention of variceal bleeding; however, up to 60% of patients respond inadequately. Carvedilol is a non-selective beta-blocker with intrinsic anti-alpha₁-adrenergic activity with a potentially greater effect on hepatic venous pressure gradient (HVPG).
Aims:
1) To compare the long-term efficacy of carvedilol and propranolol in patients with portal hypertension.
2) To assess whether the acute response to oral propranolol predicts the long-term response to these drugs.
Methods: Thirty-eight patients with cirrhosis and HVPG ≥ 12 mmHg were included.
The HVPG was measured at baseline and 90 minutes after an oral dose of 80 mg propranolol. Following randomisation, 17 patients received propranolol (mean dose 122.4 mg/day) and 21 carvedilol (mean dose 14.0 mg/day) titrated according to pulse and blood pressure response. After 12 weeks, HVPG-measurements were repeated.
Results: Acute HVPG-response to propranolol was significant -19.3 ± 12.8% (p< 0.01). Long-term treatment with propranolol and carvedilol decreased HVPG -12.5±16.7% (p< 0.01) and -18.7±16.7% (p< 0.01), respectively, with no significant difference between the two treatment-regimens (p=0.26). The frequency of long-term responders (HVPG decrease ≥ 20% or to < 12 mmHg) was 41% (propranolol) versus 62% (carvedilol) (p=0.20). There were no significant differences in ΔMAP, ΔGFR or Δweight during treatment. Using receiver operating characteristic curve analysis, the acute decrease in HVPG could not discriminate between patients with or without long-term effect of carvedilol (area under the curve (AUC) 0.54, p=0.8). In the propranolol group the discrimination was better but still insignificant (AUC 0.73, p=0.13). The acute decrease in HVPG of ≥ 12 % after oral propranolol was the best cut-off value to predict the long-term response, with a sensitivity and specificity of 71% and 78%, respectively. Neither the threshold of 12 % nor the traditional of 20% could significantly discriminate between long-term responders or non-responders (p=0.13 and p=0.11, respectively).
Conclusion: This randomized clinical trial shows no significant difference in the portal pressure-lowering effects of carvedilol and propranolol after 12 weeks of treatment. The acute response to propranolol might be a useful diagnostic tool to predict the long-term effect of propranolol but not of carvedilol.