Safety of Recombinant Activated Factor VII in Randomized Clinical Trials

N Engl J Med
Marcel Levi, M.D., Jerrold H. Levy, M.D., Henning Friis Andersen, M.Sc., and David Truloff, D.V.M.
Acceso al enlace publicador

The use of recombinant activated factor VII (rFVIIa) on an off-label basis to treat life-threatening bleeding has been associated with a perceived increased risk of thromboembolic complications. However, data from placebo-controlled trials are needed to properly assess the thromboembolic risk. To address this issue, we evaluated the rate of thromboembolic events in all published randomized, placebo-controlled trials of rFVIIa used on an off-label basis.
We analyzed data from 35 randomized clinical trials (26 studies involving patients and 9 studies involving healthy volunteers) to determine the frequency of thromboembolic
events. The data were pooled with the use of random-effects models to calculate the odds ratios and 95% confidence intervals.
Among 4468 subjects (4119 patients and 349 healthy volunteers), 498 had thromboembolic events (11.1%). Rates of arterial thromboembolic events among all 4468
subjects were higher among those who received rFVIIa than among those who received placebo (5.5% vs. 3.2%, P = 0.003). Rates of venous thromboembolic events
were similar among subjects who received rFVIIa and those who received placebo (5.3% vs. 5.7%). Among subjects who received rFVIIa, 2.9% had coronary arterial
thromboembolic events, as compared with 1.1% of those who received placebo(P = 0.002). Rates of arterial thromboembolic events were higher among subjects
who received rFVIIa than among subjects who received placebo, particularly among those who were 65 years of age or older (9.0% vs. 3.8%, P = 0.003); the rates were
especially high among subjects 75 years of age or older (10.8% vs. 4.1%, P = 0.02).
In a large and comprehensive cohort of persons in placebo-controlled trials of rFVIIa,treatment with high doses of rFVIIa on an off-label basis significantly increased the
risk of arterial but not venous thromboembolic events, especially among the elderly.
(Funded by Novo Nordisk.)

Deja un comentario