Hemodynamic effects of the angiotensin II receptor antagonist irbesartan in patients with cirrhosis and portal hypertension.
OBJECTIVE
Angiotensin II receptor antagonists have been proposed as new drugs for portal hypertension. This randomized, placebo-controlled, double-blind study aimed to assess the effect of the angiotensin II receptor antagonist irbesartan on portal and systemic hemodynamics and renal function in patients with cirrhosis.


METHODS
Thirty-six patients with cirrhosis and portal hypertension received 150 mg/d irbesartan or placebo for 1 week. Systemic hemodynamics, kidney and liver function parameters were recorded regularly; hepatic venous pressure gradient and plasma renin were assessed on days 0 and 7.


RESULTS
Irbesartan reduced the hepatic venous pressure gradient by 12.2% +/- 6.6% (P < 0.05) and mean arterial pressure by 5.3% +/- 4.0% in 13 of 18 verum patients. In 4 (22%) verum patients, arterial hypotension, accompanied by significant renal impairment, required withdrawal of irbesartan. In these patients, baseline plasma renin (P < 0.002) and cystatin C (P < 0.001) levels were higher, and creatinine clearance (P < 0.02), serum sodium (P < 0.01), and albumin (P < 0.05) were lower than in patients who tolerated irbesartan. Four of five patients with baseline renin >900 microU/mL developed treatment-limiting hypotension.


CONCLUSIONS
The angiotensin II receptor antagonist irbesartan is not advisable in patients with advanced cirrhosis and high plasma renin because it may induce arterial hypotension and only moderately reduces portal pressure.
Schepke
M
M
Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Strasse 25, D-53127 Bonn, Germany. schepke@uni-bonn.de
Werner
E
E
Biecker
E
E
Schiedermaier
P
P
Heller
J
J
Neef
M
M
Stoffel-Wagner
B
B
Hofer
U
U
Caselmann
W H
WH
Sauerbruch
T
T
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001663:Bilirubin / Q000097:blood; D001713:Biphenyl Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006975:Hypertension, Portal / Q000188:drug therapy*; D007022:Hypotension / Q000139:chemically induced; D000077405:Irbesartan; D007677:Kidney Function Tests; D008102:Liver Circulation / Q000187:drug effects*; D008103:Liver Cirrhosis / Q000150:complications*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D012083:Renin / Q000097:blood; D013777:Tetrazoles / Q000008:administration & dosage* / Q000009:adverse effects
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D013777:Tetrazoles; D012083:Renin; D000077405:Irbesartan; D001663:Bilirubin