Recombinant FVIIa treatment may increase arterial thrombosis risk
MedWire News: Off-label use of recombinant activated coagulation factor VII (rFVIIa) increases the risk for arterial but not venous thromboembolic (TE) events, especially among the elderly, show results of a comprehensive data review.
"rFVIIa is approved for the treatment of bleeding in patients with hemophilia A or B who have inhibiting antibodies to coagulation factor VIII or IX," explain Marcel Levi (University of Amsterdam, The Netherlands) and colleagues.
However, its off-label use for the treatment of life-threatening bleeding has been perceived to increase the risk for TE complications due to its potential as a hemostatic agent, they add.
To investigate whether rFVIIa does indeed increase the risk for TE events, Levi and team analyzed data from 35 published randomized, placebo-controlled trials in which rFVIIa was used off-label in the treatment and prevention of bleeding.
Of the trials assessed, 26 involved a total of 4119 patients with various clinical conditions and nine involved a total of 349 healthy volunteers.
TE events were reported in 498 (11.1%) patients overall.
The researchers found that the arterial TE event rates were significantly higher among study participants who received rFVIIa (n=2815) than among those who received placebo (n=1653), at 5.5% versus 3.2%, respectively.
Further analysis of arterial TE events revealed that significantly more participants who received rFVIIa, had coronary arterial TE events compared with those who received placebo, at 2.9% versus 1.1%.
Arterial TE event rates were particularly high among participants aged 65 years and older, the researchers note. In this age group, 9.0% of participants who received rFVIIa suffered an arterial TE event compared with 3.8% who received placebo.
The rates were even higher among participants aged 75 years and older, at 10.8% versus 4.1% for treatment with rFVIIa and placebo, respectively.
In contrast to arterial thrombosis, there was no difference in the rates of venous TE events between participants who received rFVIIa and those who received placebo, at 5.3% and 5.7%, respectively.
Writing in the NEJM Levi and co-authors conclude that "risk-benefit considerations should be evaluated before administering any hemostatic agent."
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By Laura Dean