Haemostatic drug therapies for acute primary intracerebral haemorrhage.
BACKGROUND
Because primary intracerebral haemorrhage (PICH) volume influences its outcome and a third of PICHs enlarge by a third within 24 hours of onset, early haemostatic drug therapy might improve outcome.


OBJECTIVE
To examine the clinical effectiveness and safety of haemostatic drug therapies for acute PICH in a randomised controlled trial (RCT) design.


METHODS
We searched the Cochrane Stroke Group Trials Register (last searched May 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2006), MEDLINE (1966 to August 2005) and EMBASE (1980 to August 2005). In an effort to identify further published, ongoing and unpublished studies we scanned bibliographies of relevant articles, searched international registers of clinical trials and research, and contacted authors and pharmaceutical companies.


METHODS
We sought RCTs of any haemostatic drug therapy for acute PICH, compared against placebo or open control, with relevant clinical outcome measures.


METHODS
Two review authors independently applied the inclusion criteria, reviewed the relevant studies, and extracted data from them.


RESULTS
We found four phase II RCTs, involving adults aged 18 years or over, within four hours of PICH: 116 received placebo and 373 participants received haemostatic drugs (two received epsilon-aminocaproic acid (EACA) and 371 received recombinant activated factor VII (rFVIIa)). Haemostatic drugs appeared to reduce the risk of death or dependence on the modified Rankin Scale (grades 4 to 6) within 90 days of PICH (risk reduction 0.79 (95% confidence intervals (CI) 0.67 to 0.93)), but not when assessed by the extended Glasgow Outcome Scale (risk reduction 0.90 (95%CI 0.81 to 1.01)). There was a statistically significant excess of arterial thromboembolism at 160 mcg/kg rFVIIa.


CONCLUSIONS
Current evidence for the use of haemostatic drugs in the treatment of acute PICH cannot provide clear guidelines for clinical practice. Adults with acute PICH may benefit from haemostatic therapy with rFVIIa, but the evidence on major clinical outcomes is neither robust nor precise. Large phase III RCTs of rFVIIa - and other less costly drugs - are necessary.
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GanSu Province Peoples' Hospital, Neurology and Neurosurgery, DongGang Western Road No 96, LanZhou, GanSu Province, China 730000. lzyouhonginedin@163.com
Al-Shahi
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D015119:Aminocaproic Acid / Q000627:therapeutic use*; D000933:Antifibrinolytic Agents / Q000627:therapeutic use*; D002543:Cerebral Hemorrhage / Q000188:drug therapy*; D005167:Factor VII / Q000627:therapeutic use*; D006487:Hemostasis; D006490:Hemostatics / Q000627:therapeutic use*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000627:therapeutic use
D000933:Antifibrinolytic Agents; D006490:Hemostatics; D011994:Recombinant Proteins; D005167:Factor VII; D015119:Aminocaproic Acid