Recombinant activated factor VII in chronic liver diseases: Should we be afraid of thromboembolic events?

Abstract

COMMENTARY ON: Safety of Recombinant Activated Factor VII in Randomized Clinical Trials. Levi M, Levy JH, Andersen HF, Truloff D. N Engl J Med 2010;363:179. Copyright (2010) by the Massachusetts medical Society (MMS). Abstract reprinted with permission from the MMS . http://www.ncbi.nlm.nih.gov/pubmed/21047223 Abstract: Background 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. Methods We analysed data from 35 randomized clinical trials (26 studies involving patients and nine 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. Results 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 65years of age or older (9.0% vs. 3.8%, P =0.003); the rates were especially high among subjects 75years of age or older (10.8% vs. 4.1%, P =0.02). Conclusions 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.).