Haemostatic drug therapies for acute spontaneous intracerebral haemorrhage
Abstract
Background
Because spontaneous (non‐traumatic) intracerebral haemorrhage (ICH) volume influences its outcome and a third of ICHs enlarge by a third within 24 hours of onset, early haemostatic drug therapy might improve outcome. This is an update of a Cochrane review first published in 2006.
Objectives
To examine the clinical effectiveness and safety of haemostatic drug therapies for acute ICH in a randomised controlled trial (RCT) design.
Search methods
I searched the Cochrane Stroke Group Trials Register (last searched 26 June 2009), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2009), MEDLINE (1966 to June 2009) and EMBASE (1980 to June 2009). In an effort to identify further published, ongoing and unpublished studies I scanned bibliographies of relevant articles, searched international registers of clinical trials and research, and contacted authors and pharmaceutical companies.
Selection criteria
I sought RCTs of any haemostatic drug therapy for acute ICH, compared against placebo or open control, with relevant clinical outcome measures.
Data collection and analysis
Two authors independently applied the inclusion criteria, reviewed the relevant studies, and extracted data.
Main results
I found five phase II RCTs and one phase III RCT, involving 1398 adults aged 18 years or over, within four hours of ICH onset: 423 participants received placebo and 975 participants received haemostatic drugs (two received epsilon‐aminocaproic acid (EACA) and 973 received recombinant activated factor VII (rFVIIa)). Haemostatic drugs did not significantly reduce 90‐day case fatality after ICH (risk ratio (RR) 0.85, 95% confidence interval (CI) 0.58 to 1.25), and rFVIIa did not significantly reduce death or dependence on the modified Rankin Scale (grades 4 to 6) within 90 days of ICH (RR 0.91, 95% CI 0.72 to 1.15). There was a trend towards more participants on rFVIIa experiencing thromboembolic serious adverse events (RR 1.37, 95% CI 0.74 to 2.55)
Authors' conclusions
Haemostatic drugs cannot be recommended for the treatment of acute spontaneous ICH in clinical practice, but a large RCT would be justified.
PICOs
Plain language summary
Haemostatic drug therapies for acute spontaneous intracerebral haemorrhage
More than one tenth of all strokes are caused by bleeding in the brain (known as intracerebral haemorrhage). Most of these intracerebral haemorrhages do not have an identifiable cause. The bigger the haemorrhage, the more likely it is to be fatal. Roughly one third of these haemorrhages enlarge significantly within the first 24 hours. Therefore, drugs that promote clotting ‐ known as haemostatic drugs ‐ might reduce the risk of death or being disabled after an intracerebral haemorrhage by limiting its growth, if given soon after the bleeding starts. But haemostatic drugs can cause unwanted clotting, such as heart attacks and clots in leg veins. I reviewed the evidence in 1398 adults from five phase II randomised controlled trials and one phase III randomised controlled trial. Recombinant activated factor VII (rFVIIa) was the most widely tested drug. rFVIIa did not significantly reduce the risk of a bad outcome (death or dependence) within 90 days of intracerebral haemorrhage, when compared against placebo. I found no evidence of benefit from haemostatic drug treatments for people with spontaneous intracerebral haemorrhage, though further trials appear justified.
