“Our systematic review did not show a consistent benefit of off-label use of recombinant factor VIIa in the therapeutic setting and at best only modest benefits in the prophylactic setting,” the authors conclude. “Given its potential risks, off-label use of this hemostatic agent cannot be recommended, and in most instances, it should be restricted to clinical trials.”
In their introduction, Dr. Yulia Lin at the Sunnybrook Health Sciences Centre, in Toronto, Ontario, Canada and colleagues in the UK note that many physicians apparently believe off-label use of recombinant factor VIIa is safe and effective. For example, one registry recorded that only 1% of 2700 patients treated with recombinant factor VIIa had hemophilia.
To assess outcomes in patients without hemophilia, the team identified 14 trials involving a total of 1137 patients in which recombinant factor VIIa was used prophylactically and 12 trials that included 2538 patients where it was used therapeutically.
With prophylactic use, the pooled data gave a relative mortality risk of 0.88, which was not significant. The reduction in blood loss with use of recombinant factor VIIa was modest at 276 mL, and that is “likely to be an overestimate,” the researchers report.
Results were similar and not statistically significant with therapeutic use: the relative mortality risk was 0.90 and the RR for bleeding was 1.05.
As for thromboembolic events, there was a trend toward increased risk with both types of usage: with prophylactic use the RR was 1.38 and with therapeutic use it was 1.18.
“Continued lack of clarity about the overall clinical effectiveness certainly stems from recombinant factor VIIa being genuinely less effective than was originally predicted,” Dr. Lin and colleagues state.
They conclude, “Clinically significant benefits of recombinant factor VIIa as a general hemostatic agent in patients without hemophilia remain unproven.”