Abstract

Abstract Background

Somatostatin and its derivatives are sometimes used for emergency treatment of bleeding oesophageal varices in patients with cirrhosis of the liver.

To study whether somatostatin or its analogues improve survival or reduce the need for blood transfusions in patients with bleeding oesophageal varices.

PubMed and The Cochrane Library were searched (1 November 2011). Reference lists of publications, contacts with authors.

All randomised trials comparing somatostatin or analogues with placebo or no treatment in patients suspected of acute or recent bleeding from oesophageal varices.

The outcome measures extracted were: mortality, blood transfusions, use of balloon tamponade, initial haemostasis and rebleeding. Intention‐to‐treat analyses including all randomised patients were conducted if possible; a random‐effects analysis was preferred if there was significant heterogeneity between the trials (P < 0.10). The trials were divided in two groups: trials with a low risk of bias, which had concealed allocation of patients and were double‐blind, and other trials.

We included 21 trials (2588 patients). The drugs did not reduce mortality significantly (relative risk 0.97, 95% confidence interval (CI) 0.75 to 1.25, for the trials with a low risk of bias, and 0.80, 95% CI 0.63 to 1.01, for the other trials). Units of blood transfused were 0.7 (0.2 to 1.1) less with drugs in the trials with a low risk of bias and 1.5 (0.9 to 2.0) less in the other trials. Number of patients failing initial haemostasis was reduced, relative risk 0.68 (0.54 to 0.87). Number of patients with rebleeding was not significantly reduced for the trials with a low risk of bias, relative risk 0.84 (0.52 to 1.37) while it was substantially reduced in the other trials, relative risk 0.36 (0.19 to 0.68). Use of balloon tamponade was rarely reported.

The need for blood transfusions corresponded to one half unit of blood saved per patient. It is doubtful whether this effect is worthwhile. The findings do not suggest a need for further placebo‐controlled trials of the type reviewed here. A large placebo controlled trial enrolling thousands of patients is needed if one wishes to rule out the possibility that a worthwhile effect on mortality might have been overlooked.

Author(s)

Peter C Gøtzsche, Asbjørn Hróbjartsson

Abstract

Plain language summary

Somatostatin analogues for acute bleeding oesophageal varices

Cirrhosis of the liver is a chronic, progressing disease that is most commonly caused by excessive use of alcohol or by hepatitis C infection. The liver tissue is replaced by connective tissue, which leads to loss of liver function. People with cirrhosis of the liver may develop varicose veins (enlarged blood vessels or varices) in the gullet. Bleeding varices can be life‐threatening. The hormone somatostatin, or similar drugs like octreotide and vapreotide, can be used to try to stop the bleeding. The review of 21 trials (2588 patients) found that the tested drugs did not reduce deaths. There was a small reduction in the need for blood transfusions, corresponding to one half unit of blood saved per patient. It is doubtful whether this effect is worthwhile.

Author(s)

Peter C Gøtzsche, Asbjørn Hróbjartsson

Reviewer's Conclusions

Authors' conclusions

Implications for practice

The effect of somatostatin analogues corresponded to one half unit of blood saved per patient. It is doubtful whether this effect is worthwhile.

Implications for research

Our findings do not suggest a need for further placebo‐controlled trials of the type reviewed here. A huge placebo controlled trial is needed if one wishes to rule out the possibility that a worthwhile effect on mortality may have been overlooked. Since the point estimate for relative risk was 0.97 for the trials with low risk of bias and the control group death rate was 19%, it would require 25,000 patients in each group to be 20% certain not to overlook such a difference in mortality. If one uses the most optimistic mortality estimate compatible with our data which is the lower limit of the confidence interval, it would require 1,000 patients per group not to overlook such a 25% reduction in mortality. It should be noted, however, that such a large effect on mortality is highly unlikely, given the data we have presented in this review. It is therefore difficult to justify further placebo‐controlled trials.