A randomized study of losartan vs propranolol: Effects on hepatic and systemic hemodynamics in cirrhotic patients.
OBJECTIVE
The potential use of losartan, an angiotensin II type 1 receptor blocker, in the treatment of portal hypertension is still under debate. This randomized controlled trial compared the effects of losartan vs. propranolol on portal and systemic hemodynamics in patients with cirrhosis.


METHODS
Twenty-seven compensated patients were randomized to receive losartan 25 mg/day (n = 17) or propranolol (n = 10). Hepatic venous pressure gradient (HVPG), portal blood flow (Doppler duplex ultrasound) and systemic hemodynamics were measured at baseline and after 12-week treatment. Portal resistance was calculated as HVPG/portal blood flow.


RESULTS
Propranolol induced a reduction in cardiac output (p 0.002), heart rate (p 0.0001) and HVPG [from 16.4 (+/- 4.1) to 13.1 (+/- 3.6) mmHg (p 0.07)]; six patients showed a reduction equal or greater than 20% and were considered responders. Losartan caused a decrease in HVPG [from 15.6 (+/- 4.2) to 11.8 (+/- 3.5) mmHg (p 0.002)], without changes in portal blood flow and systemic hemodynamics. Changes in HVPG correlated with variations in portal resistance (r 0.88, p < 0.0001). Losartan induced a reduction in HVPG between 10 and 19% in 5/17 patients, and 20% or more in 8/17. Five out of eight patients who respond to losartan showed severe portal hypertension, with higher baseline HVPG (equal or greater than 16 mmHg).


CONCLUSIONS
the administration of losartan in a doses of 25 mg per day may be effective in lowering portal pressure in patients with compensated cirrhosis, particularly in those with more severe portal hypertension.
Castaño
Gustavo
G
Liver Unit, Department of Internal Medicine, Hospital Argerich, Alen 963, Burzaco (1852), Buenos Aires, Argentina. castano@intramed.ent
Viudez
Pedro
P
Riccitelli
Miguel
M
Sookoian
Silvia
S
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006975:Hypertension, Portal / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011169:Portal Vein / Q000000981:diagnostic imaging; D011433:Propranolol / Q000627:therapeutic use*; D013152:Splanchnic Circulation; D016896:Treatment Outcome; D018616:Ultrasonography, Doppler, Duplex
D000959:Antihypertensive Agents; D011433:Propranolol; D019808:Losartan