Usage soars despite safety risks for some indications and a lack of efficacy in reducing mortality.
Recombinant factor VIIa (rFVIIa) is a potent procoagulant that directly activates factor X on the platelet surface, bypassing the requirement for factor VIII and several other factors in the coagulation cascade. It is FDA approved for the treatment of bleeding due to FVIII inhibitors but has been used off-label to control hemorrhage in many other clinical situations. Now, researchers have conducted two studies to determine patterns and efficacy of off-label rFVIIa use.
In the first study, investigators reviewed 12,644 discharge records of patients who received rFVIIa at 615 hospitals from 2000 through 2008. During that period, off-label use of rFVIIa increased more than 140-fold. During 2008, 97% of all uses were for off-label indications; the most common of these were adult cardiovascular surgery (27%), body trauma (18%), and intracranial hemorrhage (11%). The researchers cited prior randomized and observational studies showing that the use of rFVIIa for these indications had no effect on mortality, but that it increased the rate of thromboembolic events in adult cardiac surgery and intracranial hemorrhage.
In the second study, researchers conducted a meta-analysis of 64 randomized and observational studies to evaluate potential benefits and harms of five off-label uses of rFVIIa. The findings confirmed that use of rFVIIa in adult cardiac surgery, body trauma, and intracranial hemorrhage did not affect mortality and that it increased the rate of thromboembolic events in adult cardiac surgery and intracranial hemorrhage. In addition, rFVIIa use in liver transplantation did not affect mortality or thromboembolic events, and a small study of patients undergoing prostatectomy did not provide sufficient evidence for analyses of mortality or thrombosis.
Comment: The pathophysiology of bleeding is complex and most often reflects a loss of vascular integrity; thus, the lack of efficacy of rFVIIa in reducing mortality is not surprising. Also, the predisposition for thromboembolic events is much greater in patients with cardiovascular disease than in those with hemophilia. Unfortunately, the use of rFVIIa has been driven by the misguided perception that it would be a panacea for severe bleeding, rather than by solid evidence of safety and effectiveness.
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