Randomized comparison of long-term losartan versus propranolol in lowering portal pressure in cirrhosis

Background & Aims: It has been suggested that losartan, an angiotensin II (A-II) type I 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 (-1.0%+/- 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.