MedWire News: Treatment with recombinant activated factor VII (rFVIIa) in patients with intracerebral hemorrhage (ICH) is associated with a small increased risk for arterial thromboembolism, an analysis of clinical trial data suggests.
However, the events were typically minor and the increased risk was restricted to patients receiving higher doses of rFVIIa, indicating that rFVIIa therapy warrants continued investigation for its ability to improve clinical outcomes.
The findings are derived from the Factor Seven for Acute Hemorrhagic Stroke (FAST) trial, a phase III study in which 841 patients presenting within 3 hours of onset of symptoms of spontaneous ICH were randomly assigned to receive rFVIIa 20 or 80 µg/kg or placebo.
As previously reported, the trial showed that rFVIIa treatment was associated with a reduction in hematoma growth but failed to significantly improve outcomes as compared with placebo.
In this new analysis, Michael Diringer (Washington University, St Louis, Missouri, USA) and co-authors reviewed the frequency and risk factors for thromboembolic events (TEs) among trial participants.
There were a total of 178 arterial and 47 venous TEs, Diringer et al report in the journal Stroke.
The frequency of venous events was similar among the three treatment groups. Arterial events occurred at a similar frequency in the placebo and low-dose rFVIIa groups but were significantly more frequent in the high-dose rFVIIa group (27% and 26% vs 46%, respectively).
Factors that were significantly associated with arterial TEs included receiving high-dose rFVIIa (odds ratio [OR]=2.14 versus placebo), signs of cardiac or cerebral ischemia at presentation (OR=4.19), older age (OR=1.14 per 5-year increment), and prior use of antiplatelet agents (OR=1.83).
There were 141 myocardial events in total, 117 of which were judged to be related to study drug administration, corresponding to 13%, 9%, and 19% of the placebo, low-dose rFVIIa, and high-dose rFVIIa groups, respectively.
Finally, there were 21 cerebral infarctions, with the frequency being similar across the three treatment groups.
“These data indicate that higher doses of rFVIIa in a population at high risk for TEs are associated with a small increased risk of arterial TEs, primarily minor cardiac events,” the authors conclude.
“Demonstration of the ability of rFVIIa to improve outcome in future studies should be driven by its effectiveness in slowing bleeding overshadowing the risk of a small increase in arterial TEs.”
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