Can a subset of intracerebral hemorrhage patients benefit from hemostatic therapy with recombinant activated factor VII?

BACKGROUND AND PURPOSE In the Factor Seven for Acute Hemorrhagic Stroke (FAST) trial, 80 microg/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 microg/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 <or=70 years with baseline ICH volume <60 mL, intraventricular hemorrhage volume <5 mL, and time from onset-to-treatment <or=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 mug/kg of rFVIIa given within 2.5 hours of symptom onset.