Systematic Review: Benefits and Harms of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications

Abstract

Background Recombinant Factor VIIa (rFVIIa), a hemostatic agent approved for hemophilia, is increasingly used for off-label indications. Purpose To evaluate benefits and harms of rFVIIa use for five off-label, in-hospital indications: intracranial hemorrhage, cardiac surgery, trauma, liver transplantation, and prostatectomy. Data Sources Ten databases (including PubMed, EMBASE, and Cochrane Library) queried from the advent of each through December 2010. English language articles were analyzed. Study Selection Two reviewers independently screened titles and abstracts to identify clinical use of rFVIIa for the selected indications and identified all randomized controlled trials (RCTs) and observational studies for full-text review. Data Extraction Two reviewers independently assessed study characteristics and rated study quality and indication-wide strength of evidence. Data Synthesis Inclusion criteria were met by 17 RCTs, 33 comparative observational studies, and 23 non-comparative observational studies. Identified comparators were limited to placebo (RCTs) or usual care (observational studies). For intracerebral hemorrhage, mortality was not improved with FVIIa use across a range of rFVIIa doses. Arterial thromboembolism was increased with rFVIIa for medium-dose (risk difference 0.03 [0.01, 0.06]) and high-dose use (0.06 [0.01, 0.11]). For adult cardiac surgery, there was no mortality difference, but an increased risk of thromboembolism (0.05 [0.01, 0.10]) with rFVIIa. For body trauma, there were no differences in mortality or thromboembolism, but a reduced risk of acute respiratory distress syndrome (−0.05 [−0.02, −0.08]). Mortality and thromboembolism were consistently higher in observational studies compared to RCTs. Limitations The amount and strength of evidence was low for the majority of outcomes and indications. Publication bias could not be excluded. Conclusion Limited available evidence for five off-label indications indicates no mortality reduction with rFVIIa use. For some indications, rFVIIa increases thromboembolism. Primary Funding Source Agency for Healthcare Research and Quality

Rational Use of Recombinant Factor VIIa in Clinical Practice

“…2011 systemic review of 16 randomized controlled trials and 26 comparative observational studies and 22 noncomparative observational studies reached at a conclusion that for five indications-intracranial hemorrhage, cardiac surgery, trauma, liver transplantation and prostatectomy there was no evidence that rVIIa changed overall survival [23]. In two of these five indications i.e., intracranial hemorrhage and cardiac surgery, there was rather evidence for an increased risk of thromboembolism.…”

Use of Recombinant Factor VIIa Utilization Among a Hospitalized Pediatric Population

“…Thromboembolic complications (stroke, myocardial infarction, and other arterial thrombosis) occur at higher rates with off-label use, A review of the FDA's Adverse Event Reporting System (AERS) found 168 reports of thromboembolic events associated with rFVIIa usage between 1999-2004 (7). Multiple meta-analyses have shown a trend towards thromboembolic events when rFVIIa is administered to cardiothoracic surgery patients (8,9). The potential for thromboembolic adverse events resulted in an FDA black box warning be added to the package insert in 2005.…”

Point-of-Care Coagulation Management in Intensive Care Medicine

“…However, several conditions, such as plasma pH ≥ 7.2, fi brinogen concentration > 150 mg/dl, platelet count > 50,000/μl, hematocrit ≥ 25 %, ionized calcium concentration > 1 mmol/l and body temperature > 36 °C, should be met before factor VIIa is administered. Moreover, as highlighted in a recent systematic review, the eff ectiveness of recombinant factor VIIa in reducing the transfusion rate of allogeneic blood products or perioperative blood loss remains controversial [41].…”