Haemostatic drug therapies for acute primary intracerebral haemorrhage
Abstract
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.
Objectives
To examine the clinical effectiveness and safety of haemostatic drug therapies for acute PICH in a randomised controlled trial (RCT) design.
Search 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 In an effort to identify further published, ongoing and unpublished studies we scanned bibliographies of relevant articles, searched international registers of clinical trials and research, and contacted authors and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.
Selection criteria
We sought RCTs of any haemostatic drug therapy for acute PICH, compared against placebo or open control, with relevant clinical outcome measures.
Data collection and analysis
Two review authors independently applied the inclusion criteria, reviewed the relevant studies, and extracted data from them.
Main 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.
Authors' 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.
PICOs
Plain language summary
Haemostatic drug therapies for acute primary intracerebral haemorrhage
Up to one fifth of all strokes are caused by intracerebral haemorrhage. Most are due to primary intracerebral haemorrhage (PICH) in which there is no identifiable cause. Some PICH enlarge within the first 24 hours and the bigger the PICH the more likely it is to be fatal. Therefore, drugs that promote clotting ‐ known as haemostatic drugs ‐ might reduce the risk of death or being disabled after PICH by limiting its growth. But haemostatic drugs can cause unwanted clotting (such as heart attacks and clots in leg veins). We reviewed the evidence from four phase II randomised controlled trials involving adults. Recombinant activated factor VII (rFVIIa) was the most widely tested drug. Although rFVIIa reduced the risk of a bad outcome (death or dependence) within 90 days of PICH, the highest dose of rFVIIa caused an excess of unwanted clots in arteries. Put together, the trial results were imprecise, and the apparent benefit needs to be confirmed by much larger trials. At the moment, only one person in every eight with PICH would be eligible for rFVIIa treatment, so the use of these drugs later than four hours after PICH merits study, as does their use in people with a past history of a blood clot. Furthermore, other drugs are cheaper than rFVIIa, and perhaps equally effective, so they too may be worth testing in further large scale trials.
