Endoscopic sclerotherapy compared with no specific treatment for the primary prevention of bleeding from esophageal varices. A randomized controlled multicentre trial [ISRCTN03215899]

Abstract

Background: Since esophageal variceal bleeding is associated with a high mortality rate, prevention of bleeding might be expected to result in improved survival. The first trials to evaluate prophylactic sclerotherapy found a marked beneficial effect of prophylactic treatment. These results, however, were not generally accepted because of methodological aspects and because the reported incidence of bleeding in control subjects was considered unusually high. The objective of this study was to compare endoscopic sclerotherapy (ES) with nonactive treatment for the primary prophylaxis of esophageal variceal bleeding in patients with cirrhosis.

Methods: 166 patients with esophageal varices grade II, III of IV according to Paquet's classification, with evidence of active or progressive liver disease and without prior variceal bleeding, were randomized to groups receiving ES (n = 84) or no specific treatment (n = 82). Primary end-points were incidence of bleeding and mortality; secondary end-points were complications and costs.

Results: During a mean follow-up of 32 months variceal bleeding occurred in 25% of the patients of the ES group and in 28% of the control group. The incidence of variceal bleeding for the ES and control group was 16% and 16% at 1 year and 33% and 29% at 3 years, respectively. The 1-year survival rate was 87% for the ES group and 84% for the control group; the 3-year survival rate was 62% for each group. In the ES group one death occurred as a direct consequence of variceal bleeding compared to 9 in the other group (p = 0.01, log-rank test). Complications were comparable for the two groups. Health care costs for patients assigned to ES were estimated to be higher. Meta-analysis of a large number of trials showed that the effect of prophylactic sclerotherapy is significantly related to the baseline bleeding risk.

Conclusion: In the present trial, prophylactic sclerotherapy did not reduce the incidence of bleeding from varices in patients with liver cirrhosis and a low to moderate bleeding risk. Although sclerotherapy lowered mortality attributable to variceal bleeding, overall survival was not affected. The effect of prophylactic sclerotherapy seems dependent on the underlying bleeding risk. A beneficial effect can only be expected for patients with a high risk for bleeding.

Figure 1

Trial profile.

Figure 2

Kaplan-Meier plot showing the percentage of patients free of variceal bleeding (S: sclerotherapy group; C: control group.

Figure 3

Kaplan-Meier plot showing the percentage of surviving patients (S: sclerotherapy group; C: control group). Overall survival (black lines) was comparable. Mortality due to variceal bleeding (dotted lines) in the sclerotherapy group was significantly lower than in the control group (p = 0.01)

Figure 4

Meta-analysis (19) of the effect of prophylactic sclerotherapy on the incidence of variceal bleeding. The trials are arranged according to the baseline bleeding-risk, expressed as the odds after logarithmic transformation for the control groups.

Figure 5

Meta-analysis (19) of the effect of prophylactic sclerotherapy on the incidence of variceal bleeding. Relationship between Odds ratio for bleeding and the baseline bleeding risk.