Randomized comparison of long-term losartan versus propranolol in lowering portal pressure in cirrhosis.
OBJECTIVE
It has been suggested that losartan, an angiotensin II (A-II) type 1 receptor blocker, may have a pronounced portal pressure reducing effect, far greater than that of propranolol. This randomized controlled trial compared the hemodynamic and renal effects of continued 6-week administration of losartan (n = 25) vs. propranolol (n = 15) in portal hypertensive patients with cirrhosis treated endoscopically after a variceal bleeding episode.


METHODS
Hepatic venous pressure gradient (HVPG), systemic hemodynamics, renal function, and vasoactive factors were measured before and at 6 weeks of treatment.


RESULTS
Losartan did not reduce HVPG (-2% +/- 12%, NS) but significantly decreased mean arterial pressure (MAP, -8% +/- 10%, P = 0.001). On the contrary, propranolol significantly reduced HVPG (-10% +/- 11%, P = 0.003) and cardiac output (-16% +/- 12%, P = 0.001) but did not modify MAP (2.5% +/- 10%, NS). Losartan increased A-II levels, reduced aldosterone, and decreased glomerular filtration rate (GFR) in Child B patients. Propranolol did not modify renal function. Adverse events related to therapy were mild and similar in both groups.


CONCLUSIONS
Unlike propranolol, long-term losartan administration does not significantly reduce HVPG in patients with cirrhosis treated after a variceal bleeding episode, and it caused hypotension and reduced GFR in patients with moderate liver failure. Therefore, losartan is not an alternative to propranolol in preventing variceal rebleeding.
González-Abraldes
J
J
Hepatic Hemodynamics Laboratory, Liver Unit, Institut de Malalties Digestives, Hospital Clinic, Institut de Investigacions Biomediques August Pi i Sunyer, Universitat de Barcelona, Villaroel 170, 08036 Barcelona, Spain.
Albillos
A
A
Bañares
R
R
Del Arbol
L R
LR
Moitinho
E
E
Rodríguez
C
C
González
M
M
Escorsell
A
A
García-Pagán
J C
JC
Bosch
J
J
D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D006975:Hypertension, Portal / Q000188:drug therapy*; D008102:Liver Circulation / Q000187:drug effects; D008103:Liver Cirrhosis / Q000150:complications*; D019808:Losartan / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000008:administration & dosage* / Q000009:adverse effects; D013152:Splanchnic Circulation / Q000187:drug effects
D000959:Antihypertensive Agents; D011433:Propranolol; D003404:Creatinine; D019808:Losartan