A systematic review of randomized evidence for fibrinogen-depleting agents in acute ischemic stroke

To assess the efficacy and safety of fibrinogen-depleting agents (snake venom extracts) in the treatment of acute ischemic stroke.

A systematic review of all the relevant randomized controlled trials (RCTs) was performed. RCTs were identified from the Cochrane Stroke Group's Specialized Trial Register, additional electronic and hand searching, and personal contact with pharmaceutical companies. We included all completed and unconfounded truly or quasi-randomized trials in patients with ischemic stroke comparing fibrinogen depleting agents with control started within 14 days of the stroke onset. The Peto method was used for analysis.

Eight completed and two ongoing RCTs have been identified so far. Only three trials using ancrod (182 patients) met the inclusion criteria. Ancrod was associated with a significant reduction in early deaths (5.6% v 16%; odds ratio [OR], 0.33; 95% confidence interval [CI], 0.13 to 0.85; 2P=.02) suggesting that treatment of 100 patients would avoid about 10 early deaths. The frequency of asymptomatic intracranial hemorrhage shown by computed tomography was similar between ancrod-treated and control groups (7.6% v 9.6%; OR, 0.78; 95% CI, 0.26 to 2.33; 2P=.65). No major intracranial or extracranial hemorrhages or recurrent ischemic strokes occurred in the ancrod-allocated patients. There were nonsignificant trends in favor of ancrod in death from any cause (OR, 0.57; 95% CI, 0.27 to 1.23; 2P=.15) and death or disability (OR, 0.52; 95% CI, 0.26 to 1.03; 2P=.06) at the end of trial follow-up.

There were too few patients and outcome events to draw reliable conclusions from the present data. Although ancrod-like agents appeared promising, their routine use cannot be recommended at the moment. Two ongoing trials (including about 1,000 patients in total) will provide more data. Future trials should test simpler fixed-dose regimens to allow better generalizability.