Use of Recombinant Activated Factor VII in Patients Without Hemophilia

Abstract

Context: Benefits of recombinant activated factor VII (rFVIIa) in hemorrhage may be lost because of thromboembolic events (TAE). Method: MEDLINE, EMBASE, BIOSIS, CINAHL, Science Citation Index Expanded, clinicaltrials.gov were searched for placebo controlled trials of rFVIIa in patients without hemophilia. Reports of 22 randomized controlled trials were selected for analysis. Results were pooled using random effects models to calculate the odds ratios (OR) with 95% confidence interval (CI). Subgroup analyses were predetermined. Results: Among 3184 participants, 478 (15.0%) died and 249 (7.8%) had TAE. Additional blood transfusion was required in 517 (41.2%) of 1256 subjects. Patients receiving rFVIIa were less likely to need additional blood transfusions (OR, 0.54; 95% CI, 0.34 -0.86) than patients receiving placebo. Mortality was not increased but may be reduced (OR, 0.88; 95% CI, 0.71-1.09). Reduction in mortality was more likely if rFVIIa was given therapeutically (OR, 0.87; 95% CI, 0.70 -1.09) rather than prophylactically (OR, 1.00; 95% CI, 0.37-2.68). Differences in the pooled analysis of TAE were not statistically significant (OR, 1.17; 95% CI, 0.87-1.58) but the incidence of arterial TAE was likely higher in patients receiving rFVIIa (OR, 1.50; 95% CI, 0.93-2.41) although no differences were seen with respect to venous TAE (OR, 0.76; 95% CI, 0.49 -1.15). Conclusions: Use of rFVIIa reduces the need for blood transfusion and it may reduce mortality, especially if the dose of rFVIIa is limited to therapeutic doses of 90 g/kg. It does not increase the risk of venous thrombosis but it may increase the risk of arterial thrombosis. (Ann Surg 2008;248: 61-68)

Use of recombinant factor VIIa for the prevention and treatment of bleeding in patients without hemophilia: a systematic review and meta-analysis

“…12 The findings of our review are similar to those of a recent appraisal by Hsia and colleagues. 4 However, we grouped the RCTs by how recombinant factor VIIa was used (prophylactic or therapeutic), because the expectations of benefit and acceptance of risk in these two situations are different. This separation and greater attention to the risk of bias in the included stud ies has emphasized the degree of uncertainty about effectiveness of off-label use of recombinant factor VIIa.…”

Rational Use of Recombinant Factor VIIa in Clinical Practice

“…2008 meta-analysis of 22 randomized controlled trials of rFVIIa in 3,184 patients without hemophilia showed that those receiving rFVIIa were less likely to require additional transfusions compared to those receiving placebo [22]. However, use of rFVIIa did not significantly decrease mortality nor did it increase the incidence of thromboembolic events.…”

Recombinant Factor VIIa: An Assessment of Evidence Regarding Its Efficacy and Safety in the Off-Label Setting

“…A systematic review of RCTs, comparative and noncomparative cohort studies, retrospective cases series, and individual case reports of rFVIIa use in the setting of cardiovascular surgery also identified stroke to be the most common TAE with use of rFVIIa (2.6% of patients receiving rFVIIa experienced stroke, whereas 1.5% developed myocardial infarction, 0.8% had deep vein thrombosis, and 0.4% had intracardiac thrombosis). 41 Meta-analysis by Hsia and colleagues 42 of TAE rates across 22 clinical trials for various indications revealed a statistically significant increase in arterial thromboembolism (4.5% with rFVIIa vs 2.0% with placebo; P Ͻ .01).…”