Stroke. 2007;38:204-205
Published online before print November 16, 2006,
doi: 10.1161/01.STR.0000251797.86897.a3
(Stroke. 2007;38:204.)
© 2007 American Heart Association, Inc.
Hemostatic Drug Therapies for Acute, Nontraumatic Intracerebral Hemorrhage
Rustam Al-Shahi, MA, PhD, MRCP(UK)
Hong You, MD
From the Division of Clinical Neurosciences, Centre for Clinical Brain Sciences, School of Molecular and Clinical Medicine, University of Edinburgh, UK.
Correspondence to Dr Rustam Al-Shahi, MA PhD MRCP(UK), MRC clinician scientist, Bramwell Dott Building, Division of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK. E-mail Rustam.Al-Shahi{at}ed.ac.uk
Section Editor: Graeme J. Hankey MD, FRCP
Key Words: acute cerebral hemorrhage • intracerebral hemorrhage • emergency treatment of stroke • other stroke treatment, medical
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Introduction
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Because nontraumatic intracerebral hemorrhage (ICH) volume strongly
influences its outcome and a third of ICHs enlarge by a third
within 24 hours of onset, hemostatic drug therapy given very
soon after ICH onset might improve outcome.
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Objective
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We sought to determine the clinical effectiveness and safety
of hemostatic drug therapies for acute nontraumatic ICH in randomized
controlled trials (RCTs).
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Search Strategy
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In August 2005 we searched the Cochrane Stroke Group Trials
Register, the Cochrane Central Register of Controlled Trials,
MEDLINE from 1966 and EMBASE from 1980. We also scanned bibliographies
of relevant articles, searched international registers of clinical
trials and research, and contacted authors and pharmaceutical
companies.
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Selection Criteria
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We sought randomized controlled trials of any hemostatic drug
therapy for acute nontraumatic ICH, compared against placebo
or open control, with relevant clinical outcome measures.
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Data Collection and Analysis
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Two review authors (R.A.-S., H.Y.) independently applied the
inclusion criteria, reviewed the relevant studies, and extracted
data from them.
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Main Results
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We found 4 phase II RCTs, involving adults aged 18 years or
over, within 4 hours of nontraumatic ICH. One hundred and sixteen
study participants received placebo and 373 received hemostatic
drugs (2 received
-aminocaproic acid and 371 received recombinant
activated factor VII [rFVIIa]).
Hemostatic drugs reduced the relative risk of death within 90 days of nontraumatic ICH (risk reduction [RR] 0.67; 95% CI, 0.46 to 0.97, random effects; Figure). Specifically, rFVIIa appeared to reduce the risk of death or dependence on the modified Rankin Scale (grades 4 to 6) within 90 days of nontraumatic ICH (RR 0.79; 95% CI, 0.67 to 0.93) but not when assessed by the extended Glasgow Outcome Scale (RR 0.90; 95% CI, 0.81 to 1.01). A statistically significant excess of arterial thromboembolism at 160-µg/kg rFVIIa has been found in the trials (odds ratio 7.17, P=0.0004 versus placebo1).
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Effect of hemostatic drugs compared with placebo or open control on death at 90 days of follow-up in patients with acute, nontraumatic intracerebral hemorrhage. ATICH was a trial of -aminocaproic acid
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Implications for Clinical Practice
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The evidence for the use of hemostatic drugs in the treatment
of acute ICH is insufficient to provide clear guidelines for
practice but should influence priorities for research.
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Implications for Research
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The clinical benefits of hemostatic drugs for acute nontraumatic
ICH that have been observed among the secondary outcomes in
phase II RCTs have led to a large phase III RCT of rFVIIa (FAST
trial, NCT00127283). The FAST trial must (1) confirm or refute
the apparent effects of rFVIIa on death or dependence and (2)
provide more reliable evidence on whether any benefit from reduced
hematoma growth is offset by an increase in arterial and venous
thromboembolic events.
Evidence of the effects of less costly hemostatic drugs (for example, aprotinin, tranexamic acid, and -aminocaproic acid) in other clinical settings suggests that these drugs are also worth testing in large RCTs in people with acute nontraumatic ICH.
Note: The full text of this review is available in the Cochrane Library (for subscribers http://www.mrw.interscience.wiley. com/cochrane/clsysrev/articles/CD005951/frame.html). The full article should be cited as: You H, Al-Shahi R. Hemostatic drug therapies for acute primary intracerebral hemorrhage. Cochrane Database of Systematic Reviews. 2006, Issue 3. Art. No.: CD005951. DOI: 10.1002/14651858.CD005951.pub2.
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Acknowledgments
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We are grateful to Professor Christopher Ludlam (University
of Edinburgh) and members of the Cochrane Stroke Review Group
for their comments on the manuscript.
Sources of Funding
This review was funded by the China Scholarship Council and GanSu Province Peoples’ Hospital (to H.Y.) and a UK Medical Research Council Clinician Scientist Fellowship (to R.A.S.).
Disclosures
None.
Received September 3, 2006;
accepted September 10, 2006.
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References
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- Diringer MN, Selchen D, Davis S, Mayer SA, Brun NC, Broderick J, Skolnick BE, Steiner T; Recombinant Activated Factor VII Intracerebral Hemorrhage Trial Investigators. Safety profile of recombinant factor VIIa in patients with intracerebral hemorrhage. Stroke. 2006; 37: 623. Abstract.
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Introduction
Objective