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Acute Hemorrhagic Stroke: rFVIIa Is Not Effective

The promise shown previously for rFVIIa was not sustained in this trial.

Intracerebral hemorrhage accounts for about 15% of strokes. No effective treatment is available for these events (unlike for thrombotic strokes), but use of recombinant activated factor VII (rFVIIa) has shown promise in early trials. To further assess this agent, researchers conducted the Factor Seven for Acute Hemorrhagic Stroke (FAST) trial, a randomized, double-blind, placebo-controlled trial involving 122 institutions in 22 countries. Patients received either placebo or rFVIIa (20 µg/kg or 80 µg/kg) within 1 hour after the baseline computed tomography scan and within 4 hours after the onset of symptoms. The primary outcome was the modified Rankin scale score (the same scale used in trials evaluating thrombolytic therapy for stroke) at 90 days. All adverse events were recorded until discharge, and all serious adverse events were recorded for 90 days.

Of nearly 9000 adult patients screened, 90% were excluded for reasons including Glasgow Coma Scale score 5, planned surgical evacuation of the hematoma, secondary intracerebral hemorrhage, use of oral anticoagulants, acute sepsis, previous disability, pregnancy, and recent thromboembolic disease. Overall, 841 patients were randomized, and 821 received the assigned treatment. At 24 hours, the mean increase in volume of the intracerebral hemorrhage was 26% in the placebo group, 18% in the low-dose rFVIIa group, and 11% in the high-dose rFVIIa group; the differences between each of the active-treatment groups and the placebo group were statistically significant. However, at 72 hours, the percent increase in total lesion volume was similar among groups. Arterial thrombotic events were more common in the high-dose group. Mortality at 90 days was about 20% in all three groups, and the percentage of patients with modified Rankin scores of 5 or 6 (indicating severe disability or death) did not differ significantly among the three groups. Subgroup analyses showed that among patients younger than 70 with small bleeds who received treatment within 2.5 hours (19% of the study population), the odds ratio for a poor outcome among those who received rFVIIa compared with those who received placebo was 0.28. An editorialist concludes that the key to demonstrating benefit from rFVIIa in the future might lie in more-stringent patient selection.

Comment: In this study’s highly selected sample of patients, rFVIIa reduced hemorrhage expansion but did not reduce the incidence of poor outcomes. At present, rFVIIa cannot be recommended for use in patients with acute spontaneous intracranial hemorrhage. Of note, the role of rFVIIa in the treatment of warfarin-related hemorrhage is actively being studied, but definitive recommendations cannot yet be made.

— J. Stephen Bohan, MD, MS, FACP, FACEP

Published in Journal Watch Emergency Medicine May 16, 2008

Citation(s):

Mayer SA et al. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med 2008 May 15; 358:2127.

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• Medline abstract (Free)

Tuhrim S. Intracerebral hemorrhage — Improving outcome by reducing volume? N Engl J Med 2008 May 15; 358:2174.

• Original article (Subscription may be required)
• Medline abstract (Free)