on June 22, 2009
Published online before print June 22, 2009, doi: 10.1161/CIRCULATIONAHA.108.834275
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Submitted on September 5, 2008
From Cardiac Anaesthesia and Intensive Care Medicine, Southampton University Hospitals, Southampton, UK (R.G., M.H.); Department of Anaesthesia and Intensive Care, Papworth Hospital, Cambridge, UK (A.V.); Department of Cardiothoracic Surgery, RT Rigshospitalet, University of Copenhagen, Copenhagen, Denmark (P.S.O.); Department of Anesthesiology and Intensive Care Medicine, Charité-University Medicine Berlin, Berlin, Germany (C.v.H.); Centre for Anaesthesia, Critical Care and Pain Management, University College London, London, UK (M.M.); Division of Cardiothoracic Surgery, Alpert Medical School of Brown University, Providence, RI (F.S.); Novo Nordisk Inc, Princeton, NJ (F.B.); and Novo Nordisk A/S, Bagsvaerd, Denmark (T.A.S.). * To whom correspondence should be addressed. E-mail: ravi{at}gill-taylor.com.
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 µg/kg rFVIIa (n=35), or 80 µg/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 µg/kg, 14%; P=0.25; 80 µg/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.
Accepted on April 30, 2009
Safety and Efficacy of Recombinant Activated Factor VII. A Randomized Placebo-Controlled Trial in the Setting of Bleeding After Cardiac Surgery
Ravi Gill BM, MD, FRCA*,
Key words: cardiac surgery • cardiopulmonary bypass • coagulation • factor VIIa • hemorrhage
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