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.

Objectives: The objective of this review was to assess the effect of fibrinogen depleting agents in patients with acute ischaemic stroke.

Search strategy: We searched the Cochrane Stroke Group Trials Register (last searched May 2003). In addition we searched the following electronic databases: EMBASE (1980-October 2001), China Biological Medicine Database (CBM-disc 1981- December 2002), Chinese Stroke Trials Register (1996 - December 2002) and Index of Scientific and Technical Proceedings (Web of Science Proceedings [1990-October 2001]). We handsearched relevant journals and contacted Chinese and Japanese researchers and drug companies.

Selection criteria: Randomised and quasi-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 reviewers independently applied the inclusion criteria, assessed trial quality and extracted the data.

Main results: Five trials involving 2926 patients were included. A further trial (ESTAT) has not yet been published in full. Four trials tested ancrod and one trial tested defibrase. Allocation concealment was adequate in four trials. Fibrinogen depleting agents moderately reduced the proportion of patients who were dead or disabled at the end of follow up (Relative risk [RR] 0.90, 95% Confidence Interval [CI] 0.82 to 0.98, 2P=0.02). There was no statistically significant difference in death from all causes during the scheduled treatment period (RR 0.71, 95% CI 0.44 to 1.13) and at the end of follow-up (RR 0.98, 95% CI 0.78 to 1.24). There was a non-significant excess of symptomatic intracranial haemorrhages with treatment (RR 2.64, 95%CI 0.96 to 7.30, 2P=0.06).

Reviewer's conclusions: Fibrinogen depleting agents are promising. However more data, particularly ESTAT data, are needed before more reliable conclusions can be drawn.