LIU Ming 1 , Carl Counsell 2 , Joanna Wardlaw 2 , Peter Sandercock 2
  • 1. Department of Neurology; West China Hospital; Sichuan University; Chinese Evidence-Based Medicine/Cochrane Center; Chengdu; 610041 China2. Department of clinical Neuro-sciences; University of Edinburgh; Scotland; UK;
Ischemic stroke; randomized controlled trials; snake venom; ancrod; meta-analysis
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Objective 　To assess the efficacy and safety of fibfinogen-depleting agents (snake venom extracts) in the treatment of acute ischemic stroke.
Method 　A systematic review of all the relevant randomized controlled trails (RCTs) was performed. RCTs were identified from the Cochrane Stroke Group’s Specialized Trials Register, additional electronic and handsearching, and personal contract with pharmaceutical companies. We included all completed and unconfounded truly or quasi-randomized trials in patients with ischemic stroke comparing fibrinogen depleting agents for analysis.
Results 　Ten completed and one ongoing RCTs have been identified so far. Up to 1998, only three trials using ancrod (182 patients) met the inclusion criteria. Ancrod was associated with a significant reduction in early deaths (5.6% vs. 16%; odds ratio [OR], 0.33; 95% confidence interval [CI], 0.13 to 0.85; 2P=0.02) 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% vs. 9.6%; OR 0.78; 95%CI 0.26 to 2.33; 2P=0.65). No major intracranial or extracranial hemorrhages or recurrent ischemic strokes occurred in the ancord-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=0.15) and death or disability (OR 0.52; 95%CI 0.26 to 1.03; 2P=0.06) at the end of trial follow-up. Up to 2000, other two trials published results. This review will be updated with new trial results soon, which will provide more data.
Conclusions 　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. Future trials should test simpler fixed-dose regimens to allow better generalizability.

Citation： LIU Ming,Carl Counsell,Joanna Wardlaw,Peter Sandercock. Fibrinogen-depleting agents for acute ischemic stroke: a systematic review of randomized evidence. Chinese Journal of Evidence-Based Medicine, 2001, 01(1): 12-15. doi: Copy