Effect of recombinant Factor VIIa on outcome of acute variceal bleeding: an individual patient based meta-analysis of two controlled trials.
OBJECTIVE
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.
Gastrounit, Medical Division, Hvidovre Hospital, University of Copenhagen, Denmark. Electronic address: flemming.bendtsen@regionh.dk.
Flemming
F
Bendtsen
Gastroenterology Unit, Ospedale V Cervello, Palermo, Italy.
Gennaro
G
D'Amico
Department of Biostatistics, University of Copenhagen, Denmark.
Ea
E
Rusch
Division of Gastroenterology 3, IRCCS Cà' Granda Ospedale Maggiore Policlinico Foundation, Milano, Italy.
Roberto
R
de Franchis
Department of Biostatistics, University of Copenhagen, Denmark.
Per Kragh
PK
Andersen
Service d'Hépatologie INSERM U773, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France.
Didier
D
Lebrec
Department of Hepatogastroenterology, La Pitié-Salpêtrière Hospital, Paris, France.
Dominique
D
Thabut
Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic - Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.
Jaime
J
Bosch
D000208:Acute Disease; D000328:Adult; D000368:Aged; D004932:Esophageal and Gastric Varices / Q000188:drug therapy*; D015942:Factor VIIa / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
D011994:Recombinant Proteins; C103587:recombinant FVIIa; D015942:Factor VIIa
Acute variceal bleeding; Factor rVIIa; Meta-analysis; Outcome; Treatment