1.
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, de Franchis R, Andersen PK, Lebrec D, Thabut D, Bosch J
Journal of Hepatology. 2014;61((2)):252-9.
Abstract
BACKGROUND & AIMS Two randomized controlled studies have evaluated the effect of recombinant Factor VIIa (rFVIIa) on variceal bleeding in cirrhosis without showing significant benefit. The aim of the present study was to perform a meta-analysis of the two trials on individual patient data with special focus on high risk patients. METHODS The primary outcome measure was the effect of rFVIIa on a composite five day endpoint: failure to control bleeding, 5-day rebleeding or death. Analysis was based on intention to treat. High risk was defined as active bleeding on endoscopy while under vasoactive drug infusion and Child-Pugh score >8. RESULTS 497 patients were eligible for the meta-analysis; 308 (62%) had active variceal bleeding at endoscopy (oozing or spurting) and 283 of these had a Child-Pugh score >8. Analysis on the composite endpoint in all patients with bleeding from oesophageal varices did not show any beneficial treatment effect. However, failure rate for the primary composite end-point was significantly lower in treated patients with active bleeding at endoscopy (17%) compared to placebo (26%, p=0.049). This difference was highly significant in patients with Child-Pugh score >8 and active bleeding at endoscopy (rFVIIa 16%, placebo 27%; p=0.023). No significant treatment effect was found at 42 days. Five thromboembolic events occurred in rFVIIa treated patients compared to none in placebo treated patients. CONCLUSIONS The current meta-analysis shows a beneficial effect of rFVIIa on the primary composite endpoint of control of acute bleeding, prevention of rebleeding day 1-5 and 5-day mortality in patients with advanced cirrhosis and active bleeding from oesophageal varices at endoscopy. A major drawback of the treatment is a potential increased risk of arterial thrombo-embolic events. This treatment might be considered in patients with lack of control of bleeding after standard treatment.Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. RN 0 (Recombinant Proteins). 0 (recombinant FVIIa). EC 3-4-21-21 (Factor VIIa).
2.
Human recombinant activated factor VII for upper gastrointestinal bleeding in patients with liver diseases
Marti-Carvajal AJ, Karakitsiou DE, Salanti G
Cochrane Database of Systematic Reviews. 2012;((3):):CD004887.
Abstract
BACKGROUND Mortality from upper gastrointestinal bleeding in patients with liver disease is high. Recombinant human activated factor VII (rHuFVIIa) has been suggested for patients with liver disease and upper gastrointestinal bleeding. OBJECTIVES To assess the beneficial and harmful effects of rHuFVIIa in patients with liver disease and upper gastrointestinal bleeding. SEARCH METHODS We searched the Cochrane Hepato-Biliary Group Controlled Trials Register (December 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 4, 2011), MEDLINE (1948 to December 2011), EMBASE (1980 to December 2011), Science Citation Index Expanded (1900 to December 2011), and LILACS (December 2011). We sought additional randomised trials from the reference lists of the trials and reviews identified through the electronic searches. SELECTION CRITERIA Randomised clinical trials. DATA COLLECTION AND ANALYSIS Outcome data from randomised clinical trials were extracted and were presented using random-effects model meta-analyses. Data on the risk of bias in the included trials were also extracted. MAIN RESULTS We included two trials with 493 randomised participants with various Child-Pugh scores. The trials had a low risk of bias. The rHuFVIIa administration did not reduce the risk of mortality within five days (21/288 (7. 3%) versus 15/205 (7. 3%); risk ratio (RR) 0. 88, 95% confidence interval (CI) 0. 48 to 1. 64, I(2) = 49%) and within 42 days (5/286 (1. 7%) versus 36/205 (17. 6%); RR 1. 01, 95% CI 0. 55 to 1. 87, I(2) = 55%) when compared with placebo. Trial sequential analysis demonstrated that there is sufficient evidence to exclude that rHuFVIIa decreases mortality by 80%, but there is insufficient evidence to exclude smaller effects. The rHuFVIIa did not increase the risk of adverse events by number of patients (218/297 (74%) and 164/210 (78%); RR 0. 94, 95% CI 0. 84 to 1. 04, I(2) = 1%), serious adverse events by adverse events reported (164/590 (28%) versus 123/443 (28%); RR 0. 91, 95% CI 0. 75 to 1. 11, I(2) = 0%), and thromboembolic adverse events (16/297 (5. 4%) versus 14/210 (6. 7%); RR 0. 80, 95% CI 0. 40 to 1. 60, I(2) = 0%) when compared with placebo. AUTHORS' CONCLUSIONS We found no evidence to support or reject the administration of rHuFVIIa for patients with liver disease and upper gastrointestinal bleeding. Further adequately powered randomised clinical trials are needed in order to evaluate the proper role of rHuFVIIa for treating upper gastrointestinal bleeding in patients with liver disease. Although the results are based on trials with low risk of bias, the heterogeneity and the small sample size result in rather large confidence intervals that cannot exclude the possibility that the intervention has some beneficial or harmful effect. Further trials with alow risk of bias are required to make more confident conclusions about the effects of the intervention.
3.
The role of recombinant activated factor VII in neuro- surgical and neurocritical patients
Rama-Maceiras P, Ingelmo-Ingelmo I, Fabregas-Julia N, Hernandez-Palazon J
Neurocirugia (Asturias, Spain). 2011;22((3):):209-23.
Abstract
Central nervous system haemorrhage is a severe pathology, as a small amount of bleeding inside the brain can result in devastating consequences. Haemostatic agents might decrease the consequences of intra-cranial bleeding, whichever spontaneous, traumatic, or anticoagulation treatment etiology. Proacogulant recombinant activated factor VII (rFVIIa) has been given after central nervous system bleeding, with an off-label indication. In this update, we go over the drug mechanism of action, its role in the treatment of central nervous system haemorrhage and the published evidences regarding this subject. We carried out a literature review concerning the treatment with rFVIIa in central nervous system haemorrhage, neurocritical pathologies and neurosurgical procedures, searching in MEDLINE and in clinical trials registry: http://clinicaltrials. gov (last review September 2010), as well as performing a manual analysis of collected articles, looking for aditional references. The results of randomized clinical trials do not support the systematic administration of rFVIIa for spontaneous intracranial cerebral haemorrhage. In other central nervous system related haemorrhages, the current available data consist on retrospective studies, expert opinion or isolated case reports.
4.
A meta-analysis of the efficacy and safety of recombinant activated factor VII for patients with acute intracerebral hemorrhage without hemophilia
Yuan ZH, Jiang JK, Huang WD, Pan J, Zhu JY, Wang JZ
Journal of Clinical Neuroscience. 2010;17((6):):685-93.
Abstract
Hematoma growth is common in intracerebral hemorrhage (ICH) and is associated with a poor outcome for patients. To evaluate the efficacy and safety of recombinant activated factor VII (rFVIIa) used as a hemostatic agent in patients with ICH without hemophilia, we searched Medline, Scopus, the Cochrane Library, Clinicaltrials.gov and the Stroke Trials Directory. Five randomized controlled trials were selected for analysis. Although rFVIIa can reduce the change in ICH volume, there was no significant difference in mortality, modified Rankin Scale (mRS) score or extended Glasgow Outcome Scale (GOS-E) score in patients treated with rFVIIa or placebo. There was a significant increase in arterial thromboembolic adverse events (TAE) in patients treated with rFVIIa. There was an increase in deep vein thrombosis in patients with spontaneous ICH and traumatic ICH. In conclusion, the use of rFVIIa reduces the growth of the hematoma but does not improve patient survival or functional outcome after ICH; in addition, rFVIIa increases the incidence of arterial TAE.