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Safety of recombinant activated factor VII in randomized clinical trials.

Publication ,  Journal Article
Levi, M; Levy, JH; Andersen, HF; Truloff, D
Published in: N Engl J Med
November 4, 2010

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 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. RESULTS: Among 4468 subjects (4119 patients and 349 healthy volunteers), 401 [corrected] had thromboembolic events (9.0%). [corrected] 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). 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.).

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Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

November 4, 2010

Volume

363

Issue

19

Start / End Page

1791 / 1800

Location

United States

Related Subject Headings

  • Thrombosis
  • Thromboembolism
  • Randomized Controlled Trials as Topic
  • Off-Label Use
  • Odds Ratio
  • Middle Aged
  • Logistic Models
  • Humans
  • Hemostatics
  • Hemorrhage
 

Citation

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Levi, M., Levy, J. H., Andersen, H. F., & Truloff, D. (2010). Safety of recombinant activated factor VII in randomized clinical trials. N Engl J Med, 363(19), 1791–1800. https://doi.org/10.1056/NEJMoa1006221
Levi, Marcel, Jerrold H. Levy, Henning Friis Andersen, and David Truloff. “Safety of recombinant activated factor VII in randomized clinical trials.N Engl J Med 363, no. 19 (November 4, 2010): 1791–1800. https://doi.org/10.1056/NEJMoa1006221.
Levi M, Levy JH, Andersen HF, Truloff D. Safety of recombinant activated factor VII in randomized clinical trials. N Engl J Med. 2010 Nov 4;363(19):1791–800.
Levi, Marcel, et al. “Safety of recombinant activated factor VII in randomized clinical trials.N Engl J Med, vol. 363, no. 19, Nov. 2010, pp. 1791–800. Pubmed, doi:10.1056/NEJMoa1006221.
Levi M, Levy JH, Andersen HF, Truloff D. Safety of recombinant activated factor VII in randomized clinical trials. N Engl J Med. 2010 Nov 4;363(19):1791–1800.

Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

November 4, 2010

Volume

363

Issue

19

Start / End Page

1791 / 1800

Location

United States

Related Subject Headings

  • Thrombosis
  • Thromboembolism
  • Randomized Controlled Trials as Topic
  • Off-Label Use
  • Odds Ratio
  • Middle Aged
  • Logistic Models
  • Humans
  • Hemostatics
  • Hemorrhage