Activated recombinant factor VIIa should not be used in patients with refractory variceal bleeding: It is mostly ineffective, is expensive, and may rarely cause serious adverse events

Abstract

Activated Recombinant Factor VIIa Does Not Improve Mortality in Variceal Bleeding. Bendtsen F, D’Amico G, Rusch E, de Franchis R, Anderson PK, Lebrec D, et al. Effect of recombinant Factor VIIa on outcome of acute variceal bleeding: An individual patient based meta-analysis of two controlled trials. J Hepatol 2014; 61: 252–259. (Reproduced with Permission) Background & Aims Two randomized controlled studies have evaluated the effect of recombinant Factor VIIa (rFVIIa) on variceal bleeding in cirrhosis without showing significant benefit. The aim of the present study was to perform a meta-analysis of the two trials on individual patient data with special focus on high risk patients. Methods The primary outcome measure was the effect of rFVIIa on a composite five day endpoint: failure to control bleeding, 5-day rebleeding or death. Analysis was based on intention to treat. High risk was defined as active bleeding on endoscopy while under vasoactive drug infusion and Child-Pugh score >8. Results 497 patients were eligible for the meta-analysis; 308 (62%) had active variceal bleeding at endoscopy (oozing or spurting) and 283 of these had a Child-Pugh score >8. Analysis on the composite endpoint in all patients with bleeding from oesophageal varices did not show any beneficial treatment effect. However, failure rate for the primary composite end-point was significantly lower in treated patients with active bleeding at endoscopy (17%) compared to placebo (26%, p = 0.049). This difference was highly significant in patients with Child-Pugh score >8 and active bleeding at endoscopy (rFVIIa 16%, placebo 27%; p = 0.023). No significant treatment effect was found at 42 days. Five thromboembolic events occurred in rFVIIa treated patients compared to none in placebo treated patients. Conclusions The current meta-analysis shows a beneficial effect of rFVIIa on the primary composite endpoint of control of acute bleeding, prevention of rebleeding day 1–5 and 5-day mortality in patients with advanced cirrhosis and active bleeding from oesophageal varices at endoscopy. A major drawback of the treatment is a potential increased risk of arterial thrombo-embolic events. This treatment might be considered in patients with lack of control of bleeding after standard treatment.

EASL Clinical Practice Guidelines on prevention and management of bleeding and thrombosis in patients with cirrhosis

“…Administration of recombinant factor VIIa was potentially associated with an increased rate or arterial thromboembolic events, and it has been argued that this drug has no net clinical benefit in the setting of variceal bleeding. 218 Use of intravenous tranexamic acid has been evaluated in a large randomised placebo-controlled trial including 12,009 patients with acute upper gastrointestinal bleeding, of which nearly 50% of cases were suspected variceal bleeding. 219 The primary outcome of the trial was death due to bleeding within the first 5 days.…”

Haemostatic alterations and management of haemostasis in patients with cirrhosis

“…Similarly, recombinant factor VIIa did not confer a benefit in this setting, reinforcing the notion that pro-haemostatic therapy does not help in controlling variceal bleeding. 15,64 The standard approach to control of variceal haemorrhage is focused on endoscopic or pharmacological measures to reduce portal hypertension. 58,65,66 Therefore, transfusions or medications aimed to improve coagulation indices or support the haemostatic system do not improve outcomes and may make the situation worse.…”

Fresh frozen plasma in treating acute variceal bleeding: Not effective and likely harmful

“…Although recombinant factor VIIa and tranexamic acid are low-volume products and therefore lack volume overload issues, these prohaemostatic interventions are also not indicated as they are ineffective and associated with thrombotic risk. 18,20 It seems plausible that patients with acute variceal bleeding and modest RBC transfusion requirements do not need FFP and platelet transfusion. What needs to be done in case of massive bleeds requiring generous amounts of RBCs requires further study.…”

“…FFP and platelets do not or only marginally improve haemostasis, and blood products may do harm by exacerbation of portal hypertension and general transfusion‐related side effect. Although recombinant factor VIIa and tranexamic acid are low‐volume products and therefore lack volume overload issues, these prohaemostatic interventions are also not indicated as they are ineffective and associated with thrombotic risk 18,20 . It seems plausible that patients with acute variceal bleeding and modest RBC transfusion requirements do not need FFP and platelet transfusion.…”