Effect of recombinant Factor VIIa on outcome of acute variceal bleeding: An individual patient based meta-analysis of two controlled trials.

Bendtsen F, D'Amico G, Rusch E, et al.
J Hepatol 2014;61:252-259.
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Review by : M. Levi
NATA Review

Recombinant factor VIIa is a potent prohaemostatic agent that is licensed for the treatment of patients with inhibiting antibodies towards factor VIII or IX. It has been extensively explored for its effectiveness as a universal prohaemostatic agent in patients with severe bleeding complications (e.g. trauma, intracranial haemorrhage, major surgery) but the majority of these studies did not find a positive effect on clinically relevant outcomes. Likewise, two previous studies in patients with variceal bleeding in liver cirrhosis did not find a significant effect of the administration of recombinant factor VIIa on the number of 5-day treatment failures.

In the present analysis, the results of individual patient data from these two trials were meta-analyzed. The meta-analysis showed no significant beneficial treatment effect on the primary composite outcome (i.e. 24-hour failure to control acute bleeding or failure to prevent clinically significant rebleeding or death within 5 days). However, in the subgroup of patients with active bleeding at endoscopy, recombinant factor VIIa was more effective (primary outcome 17%) compared to placebo (primary outcome 26%; P = 0.049). Similarly, this was seen in the sub-subgroup of patients with active bleeding and cirrhosis with Child-Pugh score >8 (primary outcome in recombinant factor VIIa group 16% versus placebo group 27%; P = 0.023). The authors conclude that their analysis showed a beneficial effect of recombinant factor VIIa on the control of variceal bleeding in cirrhosis, in particular in case of active bleeding and more severe liver cirrhosis.

I think this conclusion is a bit overstated. The results are based on a subgroup of patients and need prospective validation, especially since the statistical significance is marginal. The authors assert that their results were “highly significant” in the group with more severe cirrhosis; however, it may be debatable whether a P value of 0.02 justifies this statement. Moreover, there were 5 serious thromboembolic events (3 myocardial infarctions and 2 cerebral vascular events) in the recombinant factor VIIa group (1.7%) and none in the placebo group. Also previous studies showed that the use of high dose recombinant factor VIIa in particularly an elderly population was associated with an increased risk of thromboembolic complications. Taken together, it is really premature to advocate the use of recombinant factor VIIa for variceal bleeding in cirrhosis.

– Marcel Levi

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