氯沙坦与普萘洛尔长期降低肝硬化门静脉压力的随机对照研究

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

作者信息

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

机构信息

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.

出版信息

Gastroenterology. 2001 Aug;121(2):382-8. doi: 10.1053/gast.2001.26288.

DOI:10.1053/gast.2001.26288

PMID:11487547

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.

摘要

背景与目的

有研究表明，血管紧张素II（A-II）1型受体阻滞剂氯沙坦可能具有显著降低门静脉压力的作用，其效果远强于普萘洛尔。本随机对照试验比较了门静脉高压肝硬化患者在发生静脉曲张出血事件后接受内镜治疗时，连续6周服用氯沙坦（n = 25）与普萘洛尔（n = 15）对血流动力学和肾脏的影响。

方法

在治疗前及治疗6周时测量肝静脉压力梯度（HVPG）、全身血流动力学、肾功能和血管活性因子。

结果

氯沙坦未降低HVPG（-2%±12%，无统计学意义），但显著降低平均动脉压（MAP，-8%±10%，P = 0.001）。相反，普萘洛尔显著降低HVPG（-10%±11%，P = 0.003）和心输出量（-16%±12%，P = 0.001），但未改变MAP（2.5%±10%，无统计学意义）。氯沙坦使Child B级患者的A-II水平升高、醛固酮降低、肾小球滤过率（GFR）下降。普萘洛尔未改变肾功能。两组与治疗相关的不良事件均较轻微且相似。