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Irbesartan for Treatment of Portal Hypertension?

Adding this angiotensin II–receptor antagonist to propranolol does not further reduce hepatic venous pressure gradient.

Portal hypertension–related complications are the major cause of morbidity and mortality in cirrhotic patients. β-blockers, such as propranolol, are currently used to lower portal pressure, but they do so by an average of only 15%. Angiotensin II–receptor antagonists, such as irbesartan, are another option, but their use is limited in cirrhotic patients because of their tendency to cause severe systemic arterial hypotension and subsequent renal failure. Now, investigators have tested the safety and efficacy of treating portal hypertension with a combination of low-dose propranolol and a very low starting dose of irbesartan.

The double-blind, placebo-controlled, 8-week trial involved 32 patients with cirrhosis who were randomized to receive propranolol (20 mg twice daily) with or without irbesartan (75 mg daily, titrated to 300 mg daily, as long as no signs and symptoms of hypotension or renal failure occurred). All the patients were appropriate candidates for primary or secondary prevention of variceal hemorrhage; none had severe arterial hypotension (defined by mean arterial pressure <60 mm Hg), bradycardia (<55 beats/minute), high Child-Pugh scores (>11), or hepatic encephalopathy (beyond grade 1).

Thirty-one patients completed the study (the other patient, an irbesartan recipient, was considered to be a nonresponder after he suffered a variceal bleed at week 5 that led to discontinuation of his study medication). Thirteen of 17 patients in the combination group received maximum doses of irbesartan. By week 8, mean hepatic venous pressure gradient declined in both treatment groups — from 19.6±1.5 mm Hg to 16.6±1.2 mm Hg in the combination group (P=0.037) and from 17.8±1.1 mm Hg to 15.1±1.2 mm Hg in the propranolol-monotherapy group (P=0.019). No patients in either group experienced any renal or systemic hemodynamic adverse events.

Comment: This well-designed and well-executed study demonstrates that, although irbesartan is safe to use when the dose is titrated slowly in carefully selected cirrhotic patients, coadministering it with propranolol does not lead to further reductions in portal hypertension. Clinicians continue to await the development of safe, effective agents other than β-blockers for managing portal hypertension in patients with cirrhosis.

— Atif Zaman, MD, MPH

Published in Journal Watch Gastroenterology August 22, 2008

Citation(s):

Schepke M et al. Irbesartan plus low-dose propranolol versus low-dose propranolol alone in cirrhosis: A placebo-controlled, double-blind study. Am J Gastroenterol 2008 May; 103:1152.

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