Abecasis Raquel, Kravetz David, Fassio Eduardo, Ameigeiras Beatriz, Garcia Daniel, Isla Rogelio, Landeira Graciela, Dominguez Nora, Romero Gustavo, Argonz Julio, Terg Ruben
Liver Unit, Hospital de Gastroenterología B. Udaondo, Buenos Aires, Argentina.
Hepatology. 2003 Feb;37(2):359-65. doi: 10.1053/jhep.2003.50032.
Treatment with beta-blockers fails to decrease portal pressure in nearly 40% of cirrhotic patients. Recent studies have suggested that treatment with spironolactone reduces pressure and flow in the portal and variceal systems. This trial was designed to assess if nadolol plus spironolactone is more effective than nadolol alone to prevent the first variceal bleeding. One hundred patients with medium and large varices who had never bled and were without ascites were included in a prospective, randomized, multicenter, double-blind, placebo-controlled trial. The patients were randomized into 2 groups: 51 received nadolol plus placebo (N + P) and 49 received nadolol plus spironolactone 100 mg/d (N + S). Hepatic venous pressure gradient (HVPG) and activity of the renin-aldosterone system (plasma renin activity/plasma aldosterone levels) were measured in 24 patients. There were no significant differences in the appearance of variceal bleeding and ascites between groups at a mean follow-up of 22 +/- 16 months. However, analyzing both complications together, the incidence was significantly higher in the N + P group than in the N + S group (39% vs. 20%; P <.04). Clinical ascites was also higher in patients in the N + P group than in the N + S group (21% vs. 6%; P <.04). Significant increases in plasma renin activity and plasma aldosterone levels were only observed in patients in the N + S group (P <.01). The cumulative probabilities of remaining free of bleeding and ascites were similar in both groups after 70 months of follow-up. In conclusion, these results suggest that nadolol plus spironolactone does not increase the efficacy of nadolol alone in the prophylaxis of the first variceal bleeding. However, when bleeding and ascites were considered together, the combined therapy effectively reduced the incidence of both portal-hypertensive complications.
在近40%的肝硬化患者中，使用β受体阻滞剂治疗未能降低门静脉压力。最近的研究表明，使用螺内酯治疗可降低门静脉和静脉曲张系统的压力及血流量。本试验旨在评估纳多洛尔联合螺内酯预防首次静脉曲张出血是否比单用纳多洛尔更有效。100例患有中、大型静脉曲张且从未出血且无腹水的患者被纳入一项前瞻性、随机、多中心、双盲、安慰剂对照试验。患者被随机分为两组：51例接受纳多洛尔加安慰剂（N + P），49例接受纳多洛尔加螺内酯100 mg/d（N + S）。对24例患者测量了肝静脉压力梯度（HVPG）和肾素 - 醛固酮系统活性（血浆肾素活性/血浆醛固酮水平）。在平均随访22±16个月时，两组之间静脉曲张出血和腹水的出现情况无显著差异。然而，将两种并发症综合分析，N + P组的发生率显著高于N + S组（39%对20%；P <.04）。N + P组患者的临床腹水发生率也高于N + S组（21%对6%；P <.04）。仅在N + S组患者中观察到血浆肾素活性和血浆醛固酮水平显著升高（P <.01）。随访70个月后，两组无出血和无腹水的累积概率相似。总之，这些结果表明，纳多洛尔联合螺内酯在预防首次静脉曲张出血方面并未增加单用纳多洛尔的疗效。然而，当同时考虑出血和腹水时，联合治疗有效降低了两种门静脉高压并发症的发生率。
