Fibrinogen depleting agents may help to remove blood clots in acute ischaemic stroke

Fibrinogen depleting agents are promising but unproven for acute ischaemic stroke. Most strokes are due to a blood clot blocking an artery in the brain. Fibrinogen depleting agents may help remove the blood clot to restore the blood supply to the brain and so improve the chance of making a recovery from the stroke. Fibrinogen depleting agents also reduce blood thickness (or viscosity), which also helps to improve blood flow to the brain. However, these agents can also cause serious bleeding in the brain. Evidence from this updated review, which includes eight trials involving 5701 participants, indicates that there is currently not sufficient evidence to support the routine use of fibrinogen depleting agents for the treatment of acute ischaemic stroke. Further trials are needed to determine reliably whether there is worthwhile benefit, and if so, which categories of patients are most likely to benefit.

Authors' 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.

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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.

Objectives: 

To assess the effect of fibrinogen depleting agents in patients with acute ischaemic stroke.

Search strategy: 

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.

Selection criteria: 

Randomised trials of fibrinogen depleting agents started within 14 days of stroke onset, compared with control in patients with definite or possible ischaemic stroke.

Data collection and analysis: 

Two review authors independently selected trials, assessed trial quality and extracted the data. We resolved disagreement by discussion.

Main 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).

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