Irbesartan plus low-dose propranolol versus low-dose propranolol alone in cirrhosis: a placebo-controlled, double-blind study.
OBJECTIVE
Angiotensin II receptor antagonists have been shown to moderately lower portal pressure in some patients with cirrhosis but may have adverse effects on kidney function. This study aimed at comparing the effects of a combined treatment using irbesartan plus propranolol with propranolol monotherapy on portal pressure and kidney function in patients with cirrhosis.


METHODS
Thirty-two patients were included (Child A/B/C: 13/18/1, etiology: 16 alcohol, 13 viral, 3 other; bilirubin 1.4 +/- 1.1 mg/dL, creatinine 0.86 +/- 0.20 mg/dL, baseline hepatic venous pressure gradient 18.7 +/- 5.3 mmHg). All patients received 20 mg propranolol b.i.d. Additionally, they randomly received either placebo (N = 15) or irbesartan (step-up dosage titration up to 300 mg/d, N = 17). Patients were followed at weekly intervals, re-evaluation of hepatic venous pressure gradient (HVPG) was performed after 8 wk.


RESULTS
One patient in the propranolol/irbesartan group was excluded due to variceal bleeding. No other adverse events occurred. Portal pressure declined in both groups (propranolol/irbesartan group 19.6 +/- 1.5 mmHg to 16.6 +/- 1.2 mmHg, P= 0.037, propranolol/placebo group 17.8 +/- 1.1 mmHg to 15.1 +/- 1.2 mmHg, P= 0.019). Sodium excretion significantly increased in the propranolol/irbesartan group (from 122 +/- 20 mmol/d to 230 +/- 23 mmol/d, P= 0.045), but not in the propranolol/placebo group.


CONCLUSIONS
Combination treatment of propranolol plus irbesartan is well tolerated in cirrhotic patients when titrating the angiotensin II antagonist in a step-up manner, and it increases sodium excretion in patients with compensated or moderately decompensated cirrhosis. Addition of irbesartan has no effect on portal pressure.
Schepke
Michael
M
Department of Internal Medicine I, University of Bonn, Bonn, Germany.
Wiest
Reiner
R
Flacke
Sebastian
S
Heller
Jörg
J
Stoffel-Wagner
Birgit
B
Herold
Thomas
T
Ghauri
Masooma
M
Sauerbruch
Tilman
T
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006975:Hypertension, Portal / Q000188:drug therapy*; D000077405:Irbesartan; D008103:Liver Cirrhosis / Q000188:drug therapy*; D008104:Liver Cirrhosis, Alcoholic / Q000188:drug therapy*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects; D017082:Portal Pressure / Q000187:drug effects; D011433:Propranolol / Q000008:administration & dosage*; D012083:Renin / Q000097:blood; D013777:Tetrazoles / Q000008:administration & dosage*
D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D013777:Tetrazoles; D011433:Propranolol; D012083:Renin; D000077405:Irbesartan