Chronic administration of losartan, an angiotensin II receptor antagonist, is not effective in reducing portal pressure in patients with preascitic cirrhosis.
OBJECTIVE
Plasma angiotensin II (ANG II) concentrations are elevated in cirrhosis and have been implicated as a cause of portal hypertension. We aimed to study both the systemic and portal hemodynamics, and tolerability after chronic administration of losartan, an ANG II receptor antagonist.


METHODS
Twelve patients with preascitic cirrhosis were studied: mean age of 53.8 +/- 3.3 yr; average Child-Pugh score of 5.8 +/- 0.3; alcohol etiology (5), hepatitis B/C (1/3), primary biliary cirrhosis (3). No patients were on diuretics or vasoactive medication. Hemodynamic measurements were performed at baseline and 4 weeks after daily administration of 25 mg losartan.


RESULTS
There was no significant change in the hepatic venous pressure gradient (15.4 +/- 1.5 to 13.6 +/- 1.6 mmHg, -11.7%, p = NS), despite a significant reduction in the wedge hepatic venous pressure (20.3 +/- 1.8 to 17.3 +/- 1.8 mmHg, -14.8%, p < 0.05). Cardiac output, hepatic blood flow, systemic vascular resistance, creatinine clearance, and natriuresis were unaffected. The plasma renin activity increased significantly from 2.7 +/- 0.4 to 5.2 +/- 1.1 ng/ml/h (p < 0.05). There was a significant reduction in the mean arterial pressure from 96.9 +/- 3.3 to 89.3 +/- 3.5 mmHg, -7.8 +/- 3.0% (p = 0.02), with 1 patient experiencing symptomatic hypotension.


CONCLUSIONS
Chronic administration of low-dose losartan does not lead to a significant reduction in the portal pressure gradient. Losartan is unlikely to be useful in the management of patients with early cirrhosis, who are at risk of variceal bleeding.
Tripathi
Dhiraj
D
Liver Unit, Department of Medicine, Royal Infirmary, Edinburgh, UK.
Therapondos
George
G
Lui
Hock F
HF
Johnston
Neil
N
Webb
David J
DJ
Hayes
Peter C
PC
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006439:Hemodynamics; D006801:Humans; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007668:Kidney / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017082:Portal Pressure / Q000187:drug effects*; D012084:Renin-Angiotensin System / Q000502:physiology; D016896:Treatment Outcome
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D019808:Losartan