Recombinant activated factor VII for acute intracerebral hemorrhage.
Intracerebral hemorrhage is the least treatable form of stroke and is associated with 30% to 50% mortality rate. Early hematoma growth occurs in 18% to 38% of patients scanned within 3 hours of intracerebral hemorrhage onset, and hematoma volume is an important predictor of poor outcome. Recombinant activated factor VII, a potent initiator of hemostasis, is currently approved for the treatment of bleeding in hemophilia patients with inhibitors and has also been shown to promote hemostasis in patients with normal coagulation. A recent phase IIB randomized, double-blind, placebo-controlled, dose-ranging "proof-of-concept" trial enrolled 399 intracerebral hemorrhage patients to determine whether recombinant activated factor VII can limit ongoing bleeding and improve outcome. An approximate 50% relative reduction in hematoma growth was evident with all 3 doses that were tested (40, 80, and 160 microg/kg), which translated into an average reduction in absolute intracerebral hemorrhage volume growth of approximately 5 milliliters. More importantly, recombinant activated factor VII was associated with a 38% relative reduction in mortality and significantly improved functional outcome among survivors, despite a 5% frequency of arterial thromboembolic events (primarily ischemic stroke and myocardial infarction). A large phase III trial (the FAST trial [Factor Seven for Acute Hemorrhagic Stroke Treatment]) is now in progress to confirm these findings.
Mayer
Stephan A
SA
Neurological Intensive Care Unit, Neurological Institute, Columbia University Medical Center, New York, NY 10032, USA. sam14@columbia.edu
D000208:Acute Disease; D002543:Cerebral Hemorrhage / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D017326:Clinical Trials, Phase III as Topic / Q000379:methods; D015942:Factor VIIa / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D011994:Recombinant Proteins / Q000378:metabolism / Q000627:therapeutic use*
D011994:Recombinant Proteins; D015942:Factor VIIa