1.
Safety and efficacy of recombinant activated factor VII: a randomized placebo-controlled trial in the setting of bleeding after cardiac surgery
Gill R, Herbertson M, Vuylsteke A, Olsen PS, von Heymann C, Mythen M, Sellke F, Booth F, Schmidt TA
Circulation. 2009;120((1):):21-7.
Abstract
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. METHODS AND 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.
2.
Recombinant activated factor VII in cardiac surgery
Herbertson M
Blood Coagulation & Fibrinolysis. 2004;15((Suppl 1):):S31-2.
Abstract
Adult cardiac surgery has an incidence of 1-1. 25 million procedures per year. Overall costs are in the range of 50 billion US dollars per year and are increasing. Included in these costs is an increasing burden from the use of blood and blood products. The central haemostatic problems associated with cardiac surgery are impaired platelet function associated with pre-operative medication and cardiopulmonary bypass, consumption of platelets, dilution of coagulation proteins and triggering of fibrinolysis. Anecdotal data suggest that recombinant activated factor VII (rFVIIa) has a possible role in cardiac surgery, but randomized, controlled trials are required to confirm this potential. We have undertaken a prospective, randomized, placebo-controlled trial in adult cardiac surgery with a high risk of serious haemorrhage. Drug (rFVIIa) or placebo is given after cardiopulmonary bypass and following the administration of protamine. The primary endpoints of the study are use of blood and blood products. Secondary endpoints are blood loss, length of stay in the intensive care unit and in the hospital, and survival. This study will give us further information on the potential efficacy and safety of rFVIIa in cardiac surgery.