Randomized comparison of long-term losartan versus propranolol in lowering portal pressure in cirrhosis.
Open accessAbstract
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.
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When modeling the response to antihypertensive therapies, the influence of angiotensin II on cardiac muscle must be taken into account to simulate decrease in blood pressure without increasing heart rate.
“Thus, when modeling the response to antihypertensive therapies, the influence of angiotensin II on cardiac muscle must be taken into account to simulate decrease in blood pressure without increasing heart rate, which, for instance, is the standard effect of such RAAS inhibitors as aliskiren, losartan, and enalapril (Konstam et al., 1993; Kamishirado et al., 1997; González-Abraldes et al., 2001;”
From Thoroughly Calibrated Modular Agent-Based Model of the Human Cardiovascular and Renal Systems for Blood Pressure Regulation in Health and Disease (2021) · cites this paper as González-Abraldes et al., 2001
The Systemic Hemodynamics results report that losartan lowered mean arterial pressure without changing heart rate in patients with cirrhosis; the pressure reduction was significant in Child B patients, not Child A patients. The paper attributes the hypotension to reduced peripheral resistance. It does not establish that angiotensin II’s influence on cardiac muscle must be included in a model, or that this response is standard across RAAS inhibitors. (LLM, conf=0.88)
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- Authors
- González-Abraldes, J., Albillos, A., Bañares, R., Del Arbol, L. R., Moitinho, E., Rodríguez, C., González, M., Escorsell, A., García-Pagán, J. C., & Bosch, J.
- Affiliations
- Hospital Clínic de Barcelona (ES)
- Universidad Complutense de Madrid (ES)
- Hospital Universitario Puerta del Mar (ES)
- Universidad de Alcalá (ES)
- ORCID
- Bañares, Rafael
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2001-08
- Volume
- 121
- Issue
- 2
- Pages
- 382-388
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2072755195
- Cited by
- 165
- References
- 37
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 5 · 2019: 3 · 2018: 3 · 2017: 5 · 2016: 4 · 2015: 2 · 2014: 4 · 2013: 7 · 2012: 4
- FWCI
- 10.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal Bleeding Diagnosis and Treatment
- Health Sciences › Medicine › Surgery › Abdominal vascular conditions and treatments
- Keywords
- losartan, propranolol, portal hypertension, liver cirrhosis, hepatic venous pressure gradient, variceal bleeding, angiotensin receptor blockers, beta-blockers, renal function, glomerular filtration rate, hypotension, aldosterone, cardiac output, systemic hemodynamics
- MeSH terms
- Adult, Antihypertensive Agents, Blood Pressure, Blood Urea Nitrogen, Creatinine, Female, Glomerular Filtration Rate, Humans, Hypertension, Portal, Liver Circulation, Liver Cirrhosis, Male, Middle Aged, Propranolol, Splanchnic Circulation, Losartan
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