Recombinant Factor VIIa was initially approved for bleeding in hemophiliac patients back in 1999. Over the years, there has been a big move toward off-label use. There appeared to be obvious utility in using it as an emergency hemostatic agent in trauma patients. But as with many new drugs and devices, early enthusiasm slowly gave way to more balanced judgment. Reviews during the past few years are less glowing than they were early on. So what’s really been happening over the past decade?

Researchers at Stanford tapped into a large database of patient level records from 600 hospitals around the US. They identified over 18,000 uses of Factor VIIa during a 9 year time period. By the end of the study period (2008), 97% of use was off-label! Approved use (hemophilia) increased 4-fold, while off-label use increased by 140-fold. Cardiovascular surgery and trauma tied in their amount of off-label use (both about 29% of the sample).

Does it do any good? This paper can’t directly address that question, since it does not have a good comparison group. However, looking at in-hospital mortality is revealing. Use for hemophilia (FDA approved) results in a 4% mortality rate. For trauma, the in-house mortality is 33%. The worst outcomes were with patients with an aortic aneurysm (55% mortality). 

Bottom line: This review details the administration of about $175 million worth of recombinant Factor VIIa over 9 years. Off-label use has skyrocketed despite a dearth of good reports that it actually saves lives. The Number Needed to Treat to prevent one additional bad outcome keeps getting larger with every study published. With a price tag of nearly $10,000 per dose, it’s getting harder to justify using it. I think we are seeing the beginning of the end (at least in trauma) for this powerful drug.

Reference: Off-label use of recombinant Factor VIIa in US hospitals: analysis of hospital records. Annals of Int Med 154(8):516-522, 2011.