Gastroenterology

Gastroenterology

Volume 121, Issue 2, August 2001, Pages 382-388
Gastroenterology

Liver, Pancreas, and Biliary Tract
Randomized comparison of long-term losartan versus propranolol in lowering portal pressure in cirrhosis,☆☆

https://doi.org/10.1053/gast.2001.26288Get rights and content

Abstract

Background & Aims: 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.

GASTROENTEROLOGY 2001;121:382-388

Section snippets

Patients and methods

The study was conducted in patients with cirrhosis who had bled from esophageal varices, recruited from 4 university hospitals in Spain.The final protocol was approved by the Ethical Committee of each participating hospital and the Spanish Ministry of Health and Consumer Affairs.The study was conducted following the principles of the Declaration of Helsinki.Each patient gave written informed consent to participate in the study.

Inclusion criteria were: (1) age between 18 and 75 years, (2)

Results

A total of 25 patients were randomized to receive losartan and 15 propranolol.Three patients did not complete the study because of side effects in 1 patient receiving losartan and after withdrawal of consent in 2 patients (1 propranolol, 1 losartan).Thus, the final analysis includes 23 patients receiving losartan and 14 propranolol.The main characteristics of these patients are summarized in Table 1.There were no differences between patients randomized to losartan or propranolol in any

Discussion

Portal hypertension is the result of increased hepatic resistance and portal inflow.15 Splanchnic vasoconstrictors reduce portal pressure by decreasing portal inflow and have been the mainstay of pharmacologic therapy.1 Recently, the recognition of a dynamic component in the increased hepatic resistance of cirrhosis16 has led to the introduction of vasodilators in the treatment of portal hypertension.17 Endogenous factors, such as endothelin, A-II, and alpha-adrenergic stimulus increase hepatic

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    Address requests for reprints to: Jaume Bosch, M.D., Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic, Villarroel 170, 08036 Barcelona, Spain.[email protected]; fax: (34) 93-451-52-72.

    ☆☆

    Supported in part by grants from Plan Nacional de Investigación y Desarrollo (SAF 99-0007 and SAF 2000-0219) and Fondo de Investigaciones Sanitarias (FIS 00/0444); and an award from the Hospital Clinic, Barcelona (to J.G.-A.).

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