β-肾上腺素能拮抗剂药物预防肝硬化和食管静脉曲张患者胃肠道出血。来自四项随机临床试验的589例患者的数据及预后因素分析。法意多中心研究组

Beta-adrenergic-antagonist drugs in the prevention of gastrointestinal bleeding in patients with cirrhosis and esophageal varices. An analysis of data and prognostic factors in 589 patients from four randomized clinical trials. Franco-Italian Multicenter Study Group.

作者信息

Poynard T, Calès P, Pasta L, Ideo G, Pascal J P, Pagliaro L, Lebrec D

机构信息

Hôpital Antoine Beclère, Clamart, France.

出版信息

N Engl J Med. 1991 May 30;324(22):1532-8. doi: 10.1056/NEJM199105303242202.

DOI:10.1056/NEJM199105303242202

PMID:1674104

Abstract

BACKGROUND

The value of beta-adrenergic-antagonist drug therapy for the prevention of initial episodes of gastrointestinal bleeding in patients with cirrhosis and esophageal varices is uncertain, both positive and negative study results having been reported.

METHODS

In this study, we analyzed data on individual patients from four randomized, controlled trials to assess the efficacy of this treatment. Of the 589 patients studied, 286 received a beta-adrenergic-antagonist drug (propranolol in 203 and nadolol in 83) and 303 received placebo.

RESULTS

After two years, the mean (+/- SE) percentage of patients who had had no upper gastrointestinal bleeding was 78 +/- 3 percent in the beta-adrenergic-antagonist treatment group and 65 +/- 3 percent in the control group (P = 0.002). The percentage of patients without fatal bleeding was 90 +/- 2 percent in the treatment group and 82 +/- 3 percent in the control group (P = 0.01). The percentage of patients surviving after two years was 71 +/- 3 percent in the treatment group and 68 +/- 3 percent in the control group (P = 0.34). After age and severity of cirrhosis were taken into account, the survival rate was better in the treatment group (P = 0.09). The percentage of surviving patients who had had no bleeding after two years was 62 +/- 3 percent in the treatment group and 53 +/- 3 percent in the control group (P = 0.04). Both propranolol and nadolol prevented a first episode of bleeding. Severe cirrhosis and especially the presence of ascites were associated with bleeding (P less than 0.001) and death (P less than 0.001) in both groups. The efficacy of beta-adrenergic-antagonist therapy in the prevention of bleeding (P less than 0.001) and of fatal bleeding (P = 0.004) and in the prevention of bleeding or death (P = 0.005) was the same after adjustment for cause and severity of cirrhosis, ascites, and size of varices.

CONCLUSIONS

Propranolol and nadolol are effective in preventing first bleeding and reducing the mortality rate associated with gastrointestinal bleeding in patients with cirrhosis, regardless of severity.

摘要

背景

β-肾上腺素能拮抗剂药物治疗对预防肝硬化和食管静脉曲张患者首次发生胃肠道出血的价值尚不确定，已有阳性和阴性研究结果报道。

方法

在本研究中，我们分析了来自四项随机对照试验的个体患者数据，以评估这种治疗方法的疗效。在研究的589例患者中，286例接受β-肾上腺素能拮抗剂药物治疗（203例使用普萘洛尔，83例使用纳多洛尔），303例接受安慰剂治疗。

结果

两年后，β-肾上腺素能拮抗剂治疗组未发生上消化道出血的患者平均（±标准误）百分比为78±3%，对照组为65±3%（P = 0.002）。治疗组无致命性出血的患者百分比为90±2%，对照组为82±3%（P = 0.01）。治疗组两年后的生存率为71±3%，对照组为68±3%（P = 0.34）。在考虑年龄和肝硬化严重程度后，治疗组的生存率更好（P = 0.09）。治疗组两年后无出血的存活患者百分比为62±3%，对照组为53±3%（P = 0.04）。普萘洛尔和纳多洛尔均可预防首次出血。严重肝硬化尤其是腹水的存在与两组的出血（P < 0.001）和死亡（P < 0.001）相关。在对肝硬化的病因和严重程度、腹水及静脉曲张大小进行调整后，β-肾上腺素能拮抗剂治疗在预防出血（P < 0.001）、致命性出血（P = 0.004）以及预防出血或死亡（P = 0.005）方面的疗效相同。