The role of recombinant activated factor VII in neuro- surgical and neurocritical patients
Neurocirugia (Asturias, Spain). 2011;22((3):):209-23.
Central nervous system haemorrhage is a severe pathology, as a small amount of bleeding inside the brain can result in devastating consequences. Haemostatic agents might decrease the consequences of intra-cranial bleeding, whichever spontaneous, traumatic, or anticoagulation treatment etiology. Proacogulant recombinant activated factor VII (rFVIIa) has been given after central nervous system bleeding, with an off-label indication. In this update, we go over the drug mechanism of action, its role in the treatment of central nervous system haemorrhage and the published evidences regarding this subject. We carried out a literature review concerning the treatment with rFVIIa in central nervous system haemorrhage, neurocritical pathologies and neurosurgical procedures, searching in MEDLINE and in clinical trials registry: http://clinicaltrials. gov (last review September 2010), as well as performing a manual analysis of collected articles, looking for aditional references. The results of randomized clinical trials do not support the systematic administration of rFVIIa for spontaneous intracranial cerebral haemorrhage. In other central nervous system related haemorrhages, the current available data consist on retrospective studies, expert opinion or isolated case reports.
A meta-analysis of the efficacy and safety of recombinant activated factor VII for patients with acute intracerebral hemorrhage without hemophilia
Journal of Clinical Neuroscience. 2010;17((6):):685-93.
Hematoma growth is common in intracerebral hemorrhage (ICH) and is associated with a poor outcome for patients. To evaluate the efficacy and safety of recombinant activated factor VII (rFVIIa) used as a hemostatic agent in patients with ICH without hemophilia, we searched Medline, Scopus, the Cochrane Library, Clinicaltrials.gov and the Stroke Trials Directory. Five randomized controlled trials were selected for analysis. Although rFVIIa can reduce the change in ICH volume, there was no significant difference in mortality, modified Rankin Scale (mRS) score or extended Glasgow Outcome Scale (GOS-E) score in patients treated with rFVIIa or placebo. There was a significant increase in arterial thromboembolic adverse events (TAE) in patients treated with rFVIIa. There was an increase in deep vein thrombosis in patients with spontaneous ICH and traumatic ICH. In conclusion, the use of rFVIIa reduces the growth of the hematoma but does not improve patient survival or functional outcome after ICH; in addition, rFVIIa increases the incidence of arterial TAE.
Haemostatic drug therapies for acute spontaneous intracerebral haemorrhage
Cochrane Database of Systematic Reviews. 2009;((4):):CD005951.
BACKGROUND Because spontaneous (non-traumatic) intracerebral haemorrhage (ICH) volume influences its outcome and a third of ICHs enlarge by a third within 24 hours of onset, early haemostatic drug therapy might improve outcome. This is an update of a Cochrane review first published in 2006. OBJECTIVES To examine the clinical effectiveness and safety of haemostatic drug therapies for acute ICH in a randomised controlled trial (RCT) design. SEARCH STRATEGY I searched the Cochrane Stroke Group Trials Register (last searched 26 June 2009), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2009), MEDLINE (1966 to June 2009) and EMBASE (1980 to June 2009). In an effort to identify further published, ongoing and unpublished studies I scanned bibliographies of relevant articles, searched international registers of clinical trials and research, and contacted authors and pharmaceutical companies. SELECTION CRITERIA I sought RCTs of any haemostatic drug therapy for acute ICH, compared against placebo or open control, with relevant clinical outcome measures. DATA COLLECTION AND ANALYSIS Two authors independently applied the inclusion criteria, reviewed the relevant studies, and extracted data. MAIN RESULTS I found five phase II RCTs and one phase III RCT, involving 1398 adults aged 18 years or over, within four hours of ICH onset: 423 participants received placebo and 975 participants received haemostatic drugs (two received epsilon-aminocaproic acid (EACA) and 973 received recombinant activated factor VII (rFVIIa)). Haemostatic drugs did not significantly reduce 90-day case fatality after ICH (risk ratio (RR) 0.85, 95% confidence interval (CI) 0.58 to 1.25), and rFVIIa did not significantly reduce death or dependence on the modified Rankin Scale (grades 4 to 6) within 90 days of ICH (RR 0.91, 95% CI 0.72 to 1.15). There was a trend towards more participants on rFVIIa experiencing thromboembolic serious adverse events (RR 1.37, 95% CI 0.74 to 2.55) AUTHORS' CONCLUSIONS Haemostatic drugs cannot be recommended for the treatment of acute spontaneous ICH in clinical practice, but a large RCT would be justified.