Abstract | BACKGROUND AND PURPOSE: METHODS: Data were pooled from 3 randomized placebo-controlled studies in patients diagnosed within 3 hours of spontaneous ICH who received a single dose of rFVIIa (5 to 160 microg/kg; n=371) or placebo (n=115). Clinical/laboratory evaluations, lower extremity Doppler studies, and 72-hour CT scans were used to monitor for TEs. Adverse events occurring while hospitalized and serious events occurring through day 90 were carefully reviewed. RESULTS: There was no overall increase in risk of total TEs in rFVIIa-treated patents; however, there were more arterial, but not venous, TEs in the high dose group (120 to 160 microg/kg) compared with placebo (5.4% versus 1.7%; P=0.13). Arterial events occurring within 7 days of drug administration classified as possibly or probably associated with study drug included myocardial ischemia (n=9, 8 were non-ST-segment elevation and non-Q-wave events; 2 of the 9 had sequelae) and ischemic stroke (n=9, 4 of which had likely causes other than rFVIIa). Regression analysis identified high doses (120 to 160 microg/kg) of rFVIIa as the only factor associated with arterial TEs (odds ratio=6.75; P=0.02). CONCLUSIONS: There appears to be a increased risk of arterial TEs associated with higher doses of rFVIIa in ICH patients as compared with placebo. Further studies are underway to identify specific factors associated with these events and to define the dose that maximizes benefit and minimizes risk.
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Authors | Michael N Diringer, Brett E Skolnick, Stephan A Mayer, Thorsten Steiner, Stephen M Davis, Nikolai C Brun, Joseph P Broderick |
Journal | Stroke
(Stroke)
Vol. 39
Issue 3
Pg. 850-6
(Mar 2008)
ISSN: 1524-4628 [Electronic] United States |
PMID | 18239180
(Publication Type: Comparative Study, Journal Article, Meta-Analysis)
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Chemical References |
- Recombinant Proteins
- recombinant FVIIa
- Factor VIIa
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Topics |
- Aged
- Brain Ischemia
(chemically induced, complications)
- Cerebral Hemorrhage
(drug therapy)
- Dose-Response Relationship, Drug
- Factor VIIa
(administration & dosage, adverse effects, therapeutic use)
- Female
- Humans
- Incidence
- Male
- Middle Aged
- Myocardial Ischemia
(chemically induced, complications)
- Randomized Controlled Trials as Topic
- Recombinant Proteins
(administration & dosage, adverse effects, therapeutic use)
- Regression Analysis
- Risk Assessment
- Stroke
(epidemiology, etiology)
- Thromboembolism
(chemically induced, epidemiology)
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