The effect of recombinant factor VIIa treatment in non-traumatic intracranial hemorrhage: Systematic review and meta-analysis

Abstract Background: Intracerebral haemorrhage (ICH) is a devastating condition that can be life-threatening and can result in substantial functional deterioration if not managed promptly and effectively. ICH can occur spontaneously, and in some situations, cases are managed conservatively. Recombinant Factor VIIa (rFVIIa) presented itself as a potentially effective hemostatic agent in many studies. This meta-analysis aims to evaluate the effectiveness and safety of rFVIIa in non-traumatic ICH. Method: We conducted a comprehensive literature search of Embase, PubMed, Cochrane, and Medline databases by two independent reviewers for randomized clinical trials (RCTs) comparing rFVIIa vs. placebo in non-traumatic ICH. Study selection, data extraction and risk of bias assessment using the Cochrane Risk of Bias 2 (RoB 2) tool were conducted. GRADE was used to assess overall certainty of evidence, and all analyses were conducted using random-effects models. Results: We initially 76 studies, but only five RCTs including 820 patients were included. Based on low certainty evidence, the use of rFVIIa at 80 mg/Kg vs. placebo may reduce severe disability defined as modified Rankin scale (MRS) 4-6 compared to placebo, relative risk (RR) 0.72, 95% confidence interval (CI) 0.57-0.91. There is very low certainty evidence regarding the effect of rFVIIa on 90-day mortality, RR 0.82 (95% 0.5-1.36) and the increase in ICH size at 24 hours, mean difference 1.95 cm decrease (95% CI 4.57 cm decrease to 0.67 cm increase). Based on low certainty evidence, rFVIIa may increase arterial thrombosis events, RR 1.88 (95%CI 0.99-3.57). There is very low certainty evidence regarding the effect of rFVIIa on venous thrombosis events, RR 0.63 (95% CI 0.28-1.42).Conclusion: Based on the currently available literature and with low certainty evidence, rFVIIa may reduce severe disability (MRS 4-6) compared to placebo, but may increase the risk of arterial thrombosis. There is very low certainty evidence regarding its effects on 90-day mortality, hematoma growth at 24 hours, and venous thrombosis. High-quality randomized trials are needed to highlight these potential benefits and harms.