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(Stroke. 2009;40:833.)
© 2009 American Heart Association, Inc.

Original Contributions

Can a Subset of Intracerebral Hemorrhage Patients Benefit From Hemostatic Therapy With Recombinant Activated Factor VII?

Stephan A. Mayer, MD; Stephen M. Davis, MD; Brett E. Skolnick, PhD; Nikolai C. Brun, MD, PhD; Kamilla Begtrup, MSc; Joseph P. Broderick, MD; Michael N. Diringer, MD Thorsten Steiner, MD

From the Departments of Neurology and Neurosurgery (S.A.M.), Columbia University, New York, NY; the Department of Neurology (S.M.D.), Royal Melbourne Hospital and University of Melbourne, Melbourne, Australia; the Clinical, Medical and Regulatory Department (B.E.S.), Novo Nordisk, Princeton, NJ; Clinical Development (N.C.B., K.B.), Novo Nordisk A/S, Bagsværd, Denmark; the Department of Neurology (J.P.B.), University of Cincinnati, Cincinnati, Ohio; the Department of Neurology (M.N.D.), Washington University, St Louis, Mo; and the Department of Neurology (T.S.), University of Heidelberg, Heidelberg, Germany; on behalf of the FAST trial investigators.

Correspondence to Stephan A. Mayer, MD, Neurological Intensive Care Unit, Neurological Institute, 710 West 168th Street, Unit 39, New York, NY 10032. E-mail sam14{at}columbia.edu

Background and Purpose— In the Factor Seven for Acute Hemorrhagic Stroke (FAST) trial, 80 µg/kg of recombinant activated factor VII (rFVIIa) significantly reduced intracerebral hemorrhage (ICH) expansion when given within 4 hours of onset. However, in contrast to an earlier Phase 2b study, rFVIIa did not improve survival or functional outcome. In this exploratory analysis, we hypothesized that earlier treatment and exclusion of patients with a poor prognosis at baseline might enhance the benefit of rFVIIa treatment.

Methods— Using the FAST data set, the impact of rFVIIa (80 µg/kg) on poor outcome at 3 months (modified Rankin Score of 5 or 6) was systematically evaluated within subgroups using clinically meaningful cut points in onset-to-treatment time, age, and baseline ICH and intraventricular hemorrhage volume. The effect of treatment on outcome was analyzed using logistic regression, and ICH volume was analyzed with linear mixed models.

Results— A subgroup (n=160, 19% of the FAST population) was identified comprising patients 70 years with baseline ICH volume <60 mL, intraventricular hemorrhage volume <5 mL, and time from onset-to-treatment 2.5 hours. The adjusted ORs for poor outcome with rFVIIa treatment was 0.28 (95% CI, 0.08 to 1.06), whereas the reduction in ICH growth was almost doubled (7.3±3.2 versus 3.8±1.5 mL, P=0.02). The improved effect was confirmed in an analysis of similar Phase 2 patients.

Conclusions— A prospective trial would be needed to determine whether younger patients with ICH without extensive bleeding at baseline can benefit from 80 µg/kg of rFVIIa given within 2.5 hours of symptom onset.

Key Words: hemostatic therapy • intracerebral hemorrhage • rFVIIa

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