Safety and efficacy of recombinant activated factor VII: a randomized placebo-controlled trial in the setting of bleeding after cardiac surgery.
BACKGROUND
Blood loss is a common complication of cardiac surgery. Evidence suggests that recombinant activated factor VII (rFVIIa) can decrease intractable bleeding in patients after cardiac surgery. Our objective was to investigate the safety and possible benefits of rFVIIa in patients who bleed after cardiac surgery.


RESULTS
In this phase II dose-escalation study, patients who had undergone cardiac surgery and were bleeding were randomized to receive placebo (n=68), 40 microg/kg rFVIIa (n=35), or 80 microg/kg rFVIIa (n=69). The primary end points were the number of patients suffering critical serious adverse events. Secondary end points included rates of reoperation, amount of blood loss, and transfusion of allogeneic blood. There were more critical serious adverse events in the rFVIIa groups. These differences did not reach statistical significance (placebo, 7%; 40 microg/kg, 14%; P=0.25; 80 microg/kg, 12%; P=0.43). After randomization, significantly fewer patients in the rFVIIa group underwent a reoperation as a result of bleeding (P=0.03) or required allogeneic transfusions (P=0.01).


CONCLUSIONS
On the basis of this preliminary evidence, rFVIIa may be beneficial for treating bleeding after cardiac surgery, but caution should be applied and further clinical trials are required because there is an increase in the number of critical serious adverse events, including stroke, in those patients randomized to receive rFVIIa.
Gill
Ravi
R
Cardiac Anaesthesia and Intensive Care Medicine, Southampton University Hospitals, Southampton, UK. ravi@gill-taylor.com
Herbertson
Mike
M
Vuylsteke
Alain
A
Olsen
Peter Skov
PS
von Heymann
Christian
C
Mythen
Monty
M
Sellke
Frank
F
Booth
Frank
F
Schmidt
Thomas Andersen
TA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001803:Blood Transfusion; D001026:Coronary Artery Bypass; D015942:Factor VIIa / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D019106:Postoperative Hemorrhage / Q000188:drug therapy* / Q000601:surgery; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012086:Reoperation; D016896:Treatment Outcome
D010919:Placebos; D011994:Recombinant Proteins; D015942:Factor VIIa