May 06, 2014
By David Douglas
NEW YORK - Pooled data suggest that recombinant Factor VIIa (rFVIIa) can improve outcomes of acute variceal bleeding in some patients with advanced cirrhosis and could be of use as a temporary measure, according to European investigators.
As Dr. Flemming Bendtsen told Reuters Health by email, "rFVIIa may be used in patients with severe variceal bleeding and lack of response to conventional treatment (endoscopic and vasoactive treatment), mainly as a bridge to a more definite treatment."
In an April 5 online paper in the Journal of Hepatology, Dr. Bendtsen of Hvidovre Hospital in Denmark and colleagues note that two randomized controlled studies have shown no overall significant benefit of the agent. However, they add, infusion of rFVIIa can correct reduced synthesis of this coagulation factor in patients with advanced cirrhosis and might thus be helpful in some.
To examine whether a high-risk subgroup of patients in these studies might have benefited, the researchers conducted a meta-analysis using individual data. In all, 497 patients were eligible and 308 (62%) had active variceal bleeding at endoscopy (oozing or spurting) and 283 of these had a Child-Pugh score greater than 8.
Using intention-to-treat analysis and a composite endpoint of 24-hour failure to control acute bleeding and failure to prevent clinically significant rebleeding or death within five days after the first administration, there was no overall treatment benefit.
However, this failure rate was significantly lower in treated patients with active bleeding at endoscopy compared to placebo patients (17% vs. 26%, respectively). This was also true of patients with Child-Pugh score beyond 8 and active bleeding at endoscopy. By six weeks there was no significant treatment effect on rebleeding rate or mortality.
Also, although there were no thromboembolic events in placebo patients, there were five in the active treatment group. The researchers note, "Three of these patients had precipitating factors like heavy smoking, diabetes mellitus for years and treatment with Terlipressin, but in two patients no predisposing factors could be identified."
They suggest that a lower dose than the 120 mcg/kg employed in the current study might be safer and "future trials of rFVIIa should closely monitor risk of thrombo-embolic events including risk of portal venous thrombosis."
Given these results, the team concludes, "Treatment with factor rFVIIa might be considered in Child-Pugh B and C patients, who have lack of control of bleeding after standard treatment."
Commenting on the findings by email, Dr. Jerrold H. Levy of Duke University School of Medicine in Durham, North Carolina pointed out, "Life threatening exsanguination is 100% fatal, so strategies such as this are important to consider - but risk versus benefit considerations are critical."
Dr. Levy, an anesthesiologist and co-director of the cardiothoracic ICU, added, "All prothrombotic issues have potential side effects, including transfused allogeneic blood, but they are also used in life threatening situations where patients are already destined to adverse outcomes."
J Hepatol 2014.
(c) Copyright Thomson Reuters 2014. Click For Restrictions - http://about.reuters.com/fulllegal.asp