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

Abstract

Background: The benefits and risks of off-label use of recombinant factor VIIa in patients without hemophilia are contested. We performed a systematic review to assess the effectiveness and safety of such use.

Methods: We searched electronic databases including MEDLINE, EMBASE and CENTRAL for randomized controlled trials comparing recombinant factor VIIa with placebo in any patient population except those with hemophilia up to January 2010. Eligible articles were assessed for inclusion, data were extracted, and study quality was evaluated. Outcomes included mortality, blood loss, requirements for red blood cell transfusion, number of patients transfused and thromboembolic events.

Results: We identified 26 trials: 14 on off-label prophylactic use of recombinant factor VIIa (n = 1137) and 12 on off-label therapeutic use (n = 2538). In the studies on prophylactic use, we found no significant difference in mortality or thromboembolic events between the treatment and placebo groups. We found modest benefits favouring recombinant factor VIIa in blood loss (weighted mean difference -276 mL, 95% confidence interval [CI] -411 to -141 mL), red blood cell transfusion (weighted mean difference -281 mL, 95% CI -433 to -129 mL) and number of patients transfused (relative risk 0.71, 95% CI 0.50 to 0.99). In the therapeutic trials, we found a nonsignificant decrease in mortality and a nonsignificant increase in thromboembolic events but no difference in control of bleeding or red blood cell transfusion.

Interpretation: Clinically significant benefits of recombinant factor VIIa as a general hemostatic agent in patients without hemophilia remain unproven. Given its potential risks, such use cannot be recommended, and in most cases, it should be restricted to clinical trials.

Figure 1:

Selection of randomized controlled trials (RCTs).

Figure 2:

Pooled analysis of mortality data from randomized controlled trials of the prophylactic use (top panel) and therapeutic use (bottom panel) of recombinant factor VIIa in patients without hemophilia. A value below 1.0 indicates a decreased risk of death with recombinant factor VIIa. *Not estimable. CI = confidence interval, OR = odds ratio, RR = risk ratio.

Figure 3:

Pooled analysis of data on thromboembolic events from randomized controlled trials of the prophylactic use (top panel) and therapeutic use (bottom panel) of recombinant factor VIIa in patients without hemophilia. A value below 1.0 indicates a decreased risk of thromboembolic event with recombinant factor VIIa. *Not estimable. CI = confidence interval, OR = odds ratio, RR = risk ratio.