Stroke. 2008;39:514-515
Published online before print January 10, 2008,
doi: 10.1161/STROKEAHA.107.496802
(Stroke. 2008;39:514.)
© 2008 American Heart Association, Inc.
Calcium Antagonists for Aneurysmal Subarachnoid Hemorrhage
Sanne M. Dorhout Mees, MD;
Gabriel J.E. Rinkel;
Valery L. Feigin, MD, MSc, PhD;
Ale Algra, MD;
Walter M. van den Bergh, MD, PhD;
Marinus Vermeulen, MD
Jan van Gijn, MD, FRCP, FRCP(E)
From the Department of Neurology (S.M.D.M., G.J.E.R., W.M.v.d.B, J.v.G.), Rudolf Magnus Institute of Neuroscience; the Julius Center for Health Sciences and Primary Care (A.A.), University Medical Center Utrecht; the Academic Medical Center (M.V.), Amsterdam, the Netherlands; and the School of Population Health (V.L.F.), The University of Auckland, New Zealand.
Correspondence to Prof Gabriel J.E. Rinkel, MD, Professor of Neurology, Department of Neurology, University Medical Centre Utrecht, PO Box 85500, Utrecht, the Netherlands. E-mail G.J.E.Rinkel{at}umcutrecht.nl
Graeme J. Hankey MD, FRCP Section Editor:
Key Words: randomized controlled trials • subarachnoid hemorrhage • calcium antagonists
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Introduction
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Secondary ischemia is a frequent cause of poor outcome in patients
with subarachnoid hemorrhage (SAH). Its pathogenesis has been
incompletely elucidated, but vasospasm probably is a contributing
factor. Experimental studies have suggested that calcium antagonists
can prevent or reverse vasospasm and have neuroprotective properties.
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Objective
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The objective of this study was to determine, in a systematic
review of all randomized clinical trials (RCT), whether calcium
antagonists improve outcome in patients with aneurysmal SAH.
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Search Strategy
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We aimed to include all RCTs on calcium antagonists in aneurysmal
SAH. The Cochrane Stroke Group Trials Register (last searched
April 2006), MEDLINE (1966 to March 2006), and EMBASE (1980
to March 2006) were searched. We hand searched 2 Russian journals
(1990 to 2003), and contacted trialists and pharmaceutical companies
in 1995 and 1996.
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Selection Criteria
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We included RCTs comparing calcium antagonists with control,
or a second calcium antagonist (magnesium sulfate) versus control
in addition to another calcium antagonist (nimodipine) in both
the intervention and control groups.
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Data Collection and Analysis
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Two reviewers independently extracted the data and assessed
trial quality. Trialists were contacted to obtain missing information.
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Main Results
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Sixteen trials (4 new since the previous review), involving
3361 patients, were included in the review; 3 trials studied
magnesium sulfate in addition to nimodipine. In most included
RCTs the aneurysms were treated by surgical clipping. Overall,
calcium antagonists reduced the risk of poor outcome: the relative
risk (RR) was 0.81 (95% confidence interval [CI] 0.72 to 0.92);
the corresponding number of patients needed to treat was 19
(95% CI 1 to 51;
Figure). For oral nimodipine alone the RR was
0.67 (95% CI 0.55 to 0.81), for other calcium antagonists or
intravenous administration of nimodipine the results were not
statistically significant. Calcium antagonists reduced the occurrence
of secondary ischemia (RR: 0.66, 95% CI 0.59 to 0.75) and showed
a favorable trend for case fatality. For magnesium in addition
to standard treatment with nimodipine, the RR was 0.75 (95%
CI 0.57 to 1.00) for poor outcome (
Figure, bottom) and 0.66
(95% CI 0.45 to 0.96) for secondary ischemia.
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Discussion
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Calcium antagonists reduce the risk of poor outcome and secondary
ischemia after aneurysmal SAH. The results for "poor outcome"
depend largely on a single large trial of oral nimodipine; the
evidence for other calcium antagonists is inconclusive. The
evidence for nimodipine is not beyond all doubt, but given the
potential benefits and modest risks of this treatment, oral
nimodipine is currently indicated in patients with aneurysmal
SAH. Intravenous administration of calcium antagonists cannot
be recommended for routine practice on the basis of the present
evidence. The aneurysms of most patients included in this review
were treated by surgical clipping instead of endovascular coiling.
Possible differences in effects of calcium antagonist on outcome
between patients whose aneurysms are treated by coiling or clipping
are not known. Magnesium sulfate is a promising agent, but more
evidence is needed before definite conclusions can be drawn.
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Implications for Clinical Practice
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Based on the current evidence, the authors recommend oral nimodipine
(60 mg every 4 hours, to be continued for 3 weeks) as standard
treatment in patients with aneurysmal subarachnoid hemorrhage.
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).1
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Acknowledgments
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Disclosures
None.
Received June 15, 2007;
accepted June 20, 2007.
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Reference
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- Sanne M. Dorhout Mees, Gabriel J.E. Rinkel, Valery L. Feigin, Ale Algra, Walter M. van den Bergh, Marinus Vermeulen, Jan van Gijn. Calcium antagonists for aneurysmal subarachnoid hemorrhage. Cochrane Database Syst Rev. 2007 July 18;(3):CD000277.
Top
Introduction
Objective