title: Fibrinogen depleting agents for acute ischaemic stroke.
abstract: BACKGROUND
  Fibrinogen depleting agents reduce fibrinogen in blood plasma, reduce blood viscosity and hence increase blood flow. This may help remove the blood clot blocking the artery and re-establish blood flow to the affected area of the brain after an ischaemic stroke. The risk of haemorrhage may be less than with thrombolytic agents. This is an update of a Cochrane review first published in 1997 and last updated in 2003.
  
  
  OBJECTIVE
  To assess the effect of fibrinogen depleting agents in patients with acute ischaemic stroke.
  
  
  METHODS
  We searched the Cochrane Stroke Group Trials Register (July 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 7), the Chinese Stroke Trials Register (September 2011), MEDLINE (1950 to July 2011), EMBASE (1980 to July 2011) and Web of Science Conference Proceedings (1990 to July 2011). In addition, we searched six Chinese databases, four ongoing trials registers (July 2011) and relevant reference lists. For previous versions of the review, we handsearched journals and contacted researchers in China and Japan and relevant drug companies.
  
  
  METHODS
  Randomised trials of fibrinogen depleting agents started within 14 days of stroke onset, compared with control in patients with definite or possible ischaemic stroke.
  
  
  METHODS
  Two review authors independently selected trials, assessed trial quality and extracted the data. We resolved disagreement by discussion.
  
  
  RESULTS
  We included eight trials involving 5701 patients. Six trials tested ancrod and two trials tested defibrase (patients were treated for less than three hours to less than 48 hours). Allocation concealment was adequate in seven trials. Fibrinogen depleting agents marginally reduced the proportion of patients who were dead or disabled at the end of follow-up (risk ratio (RR) 0.95, 95% confidence Interval (CI) 0.90 to 0.99, 2P = 0.02). There was no statistically significant difference in death from all causes during the scheduled treatment or follow-up period. There were fewer stroke recurrences in the treatment group than in the control group (RR 0.67, 95% CI 0.49 to 0.92, 2P = 0.01). However, symptomatic intracranial haemorrhage was about twice as common in the treatment group compared with the control group (RR 2.42, 95% CI 1.65 to 3.56, 2P < 0.00001).
  
  
  CONCLUSIONS
  The current evidence is promising but not yet sufficiently robust to support the routine use of fibrinogen depleting agents for the treatment of acute ischaemic stroke. Further trials are needed to determine whether there is worthwhile benefit, and if so, which categories of patients are most likely to benefit.
authors.affiliation: Department of Neurology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Zilong
authors.initials: Z
authors.lastname: Hao
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Carl
authors.initials: C
authors.lastname: Counsell
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Wardlaw
authors.forename: Sen
authors.initials: S
authors.lastname: Lin
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000721:Ancrod / Q000009:adverse effects / Q000627:therapeutic use*; D012103:Batroxobin / Q000009:adverse effects / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000188:drug therapy*; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D020300:Intracranial Hemorrhages / Q000139:chemically induced; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000188:drug therapy* / Q000401:mortality
chemical_list: D005343:Fibrinolytic Agents; D000721:Ancrod; D012103:Batroxobin