Recombinant activated factor VII increases stroke in cardiac surgery: a meta-analysis.

Prohemostatic interventions, in particular antifibrinolytic treatment, have been studied extensively in patients undergoing cardiac surgery. Antifibrinolytic treatment has been shown repeatedly to be effective in reducing perioperative blood losses, transfusion requirements, and clinically relevant outcomes, such as reoperation, perioperative complications and mortality. Another prohemostatic option is recombinant factor VIIa (rFVIIa), which is used in case of excessive blood loss, when all other treatment options have failed. Due to the mostly anecdotal reports of success of this intervention, many studies have been initiated to demonstrate reduction of blood losses and clinically relevant adverse outcomes in several perioperative settings. Recent analyses, however, have shown that rFVIIa may be associated with an increased risk of thromboembolic complications. Ponschab et al. performed a meta-analysis of 6 studies evaluating the administration of rFVIIa in patients undergoing cardiac surgery. The meta-analysis included 470 patients undergoing various cardiac interventions, including complex non-coronary cardiac surgery, aortic dissection, and varied procedures. The authors found an increased risk of ischemic stroke in patients treated with rFVIIa (4.7% versus 0.9% in the control group; odds ratio 3.69, 95% confidence interval 1.1-12.4) but mortality was not different between rFVIIa treated patients and controls. On the efficacy side, there was a trend towards lower reexploration rates in patients who received rFVIIa.

Based on these findings the authors’ conclusion that routine administration of rFVIIa in cardiac surgery patients cannot be recommended is justified. Although it was not clear whether ischemic stroke was systematically assessed and objectively diagnosed in the various studies, and despite the fact that the meta-analysis included studies representing a wide variety of procedures, the safety data are worrisome. Indeed, the data support the policy that rFVIIa should only be considered in cases of excessive blood losses refractory to conventional therapy that may lead to death when all other treatment options are exhausted.

– Marcel Levi