Purpose: To characterize patterns of rFVIIa use in adult cardiac surgery and evaluate its comparative safety and effectiveness versus usual care.
Methods: Patterns of Use: We evaluated the use of rFVIIa for cardiac surgery from the 2000-8 Premier Prospectives administrative database, a representative sample of 615 US hospitals. Systematic Review: We sought English-language articles comparing rFVIIa versus usual care in cardiac surgery from 10 databases (e.g., PubMed, DARE, EMBASE, BIOSIS) through 2/2009. Where appropriate, we calculated summary mean arcsine differences between rFVIIa and usual care using random effects models.
Results: Patterns of Use: In the Premier data, rVIIa was first used for cardiac surgery in 2002 and by 2008 it was the leading indication, accounting for 27% of use (5,860 cases). In-hospital mortality was 23%. Systematic Review: We identified 4,967 citations; 16 studies with 1,249 rFVIIa-treated patients and 1,042 usual care patients met inclusion criteria (1 RCT, 6 comparative observational studies, 8 non-comparative observational studies; 1 unpublished RCT was included in sensitivity analyses). rFVIIa was used for prophylaxis of bleeding in the published RCT but was used as treatment for severe/refractory bleeding in all other studies—a factor that may limit the applicability of the RCT results. Mean dose ranged widely: 17-103 mcg/kg. There was no difference in mortality between rFVIIa and usual care patients (arcsine mean difference, -0.051; 95%CI: -0.156 to 0.054). rVIIa patients may experience an increased rate of thromboembolism compared with usual care (arcsine mean difference 0.137, 95%CI: -0.001 to 0.276; arcsine mean difference including the unpublished RCT 0.140, 95%CI: 0.038 to 0.242). The paucity and heterogeneity of the included studies limited our ability to find a consistent effect of rVIIa use on other outcomes (e.g., red blood cell transfusions, ICU length of stay), determine the comparative safety and efficacy in key patient subpopulations, or evaluate the effects of rFVIIa dosage and timing.
Conclusions: Cardiac surgery is the leading indication for rVIIa use despite the lack of compelling evidence of clinical benefit and a possible increased risk of thromboembolism. Limitations of the available evidence should restrain enthusiasm for wider routine use of rFVIIa in cardiac surgery until further data become available.
Candidate for the Lee B. Lusted Student Prize Competition