Stroke. 2009;40:e622-e623
Published online before print September 17, 2009,
doi: 10.1161/STROKEAHA.109.561860
(Stroke. 2009;40:e622.)
© 2009 American Heart Association, Inc.
Interventions in the Management of Serum Lipids for Preventing Stroke Recurrence
Bradley N. Manktelow, PhD
John F. Potter, DM, FRCP
From the Department of Health Sciences (B.N.M.), University of Leicester; and the School of Medicine, Health Policy, and Practice (J.F.P.), University of East Anglia, UK.
Correspondence to Professor John Potter, School of Medicine, Health Policy, and Practice, University of East Anglia, Norfolk NR4 7TJ, UK. E-mail john.potter{at}uea.ac.uk
Graeme J. Hankey MD, FRCP Section Editor:
Key Words: stroke recurrence • statin • lipids • systematic review
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Introduction
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Studies have shown interventions that reduce total and low-density
lipoprotein cholesterol levels also decrease subsequent coronary
heart disease (CHD) and stroke events in those with a history
of CHD. However, it is uncertain whether pharmacological alteration
of lipid levels in those with a history of cerebrovascular disease
can prevent recurrence of either stroke or subsequent cardiovascular
events.
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Objectives
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This systematic review investigated the effect of drug therapy
to alter serum lipids in preventing subsequent cardiovascular
disease and stroke recurrence in patients with a history of
stroke or transient ischemia attacks (TIA).
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Search Strategy
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We searched the Cochrane Stroke Group Trials Register, the Cochrane
Central Register of Controlled Trials, MEDLINE, and EMBASE.
We also contacted pharmaceutical companies known to produce
a lipid-lowering agent for information on relevant publications
or unpublished work. Randomized trials of participants aged
18 years and over with a history of stroke or TIA were included.
The two review authors independently selected the trials, assessed their quality, and extracted the data. All analyses were carried out using Review Manage 5.0. Differences in outcome between the treatment groups were quantified using the Peto odds ratios (OR), with 95% confidence intervals (CI), from a fixed effects model.
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Main Results
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Eight trials involving approximately 10 000 participants fit
the entry criteria. The active interventions were pravastatin,
atorvastatin, or simvastatin in 5 trials, clofibrate in 2, and
conjugated estrogen. In those with a previous history of stroke
or TIA there was no evidence of a difference overall in stroke
recurrence with therapy (OR 0.92, 95% CI 0.81 to 1.04), but
statin-based therapy had a marginal benefit in reducing subsequent
cerebrovascular events (OR 0.88, 95% CI 0.77 to 1.00;
Figure).
However, analysis by type of subsequent stroke (two studies)
showed evidence for a protective effect of statins for ischemic
stroke (OR 0.78, 95% CI 0.67 to 0.92) but evidence for an increased
risk of hemorrhagic stroke (OR 1.72, 95% CI 1.20 to 2.46). There
was no evidence that statin or other therapy reduced all-cause
mortality or sudden death (OR 1.00, 95% CI 0.83 to 1.20). There
was evidence, though, of a reduction in subsequent serious vascular
events (OR 0.74, 95% CI 0.67 to 0.82) in the 3 statin trials.
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Figure. Effect of drug therapy to alter serum lipids on subsequent cerebrovascular events in those with a history of stroke or TIA, by drug type.
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Conclusions
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The evidence suggests that statins, but not other lipid lowering
therapy, in patients with a history of ischemic stroke or TIA
significantly reduces subsequent major coronary events but only
marginally reduces the risk of stroke recurrence. There is no
clear evidence of beneficial effect from statins in those with
previous hemorrhagic stroke, and it is unclear when after ischemic
stroke statins should be started. In view of this and the evidence
of the benefit of statin therapy in those with a history of
CHD, patients with ischemic stroke or TIA, with or without a
history of established CHD, should receive statin therapy.
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Implications for Clinical Practice and Future Research
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There is good evidence for a beneficial effect of statin therapy
in those under the age of 80 years with a previous nondisabling
ischemic stroke or TIA, but not hemorrhagic stroke, who have
baseline total cholesterol levels >3.5 mmols/L in terms of
reducing subsequent serious vascular events. The data also suggested
a marginal benefit of statins in reducing future cerebrovascular
events, but not overall mortality. In view of this evidence
it is recommended that all ischemic stroke or TIA patients aged
at least up to 80 years should receive statin therapy as part
of a secondary prevention program.
Further work is needed to answer important unresolved questions such as (1) what is the potential role of statins for those patients with a previous cerebral hemorrhage, (2) when after the cerebrovascular event therapy to alter lipid levels should be started, (3) at what baseline lipid levels treatment should be commenced, (4) what level of reduction should be aimed for, and (5) whether the very elderly (those aged over 80 years) stroke patient benefits to the same extent as a younger counterpart.
Full details and all graphical plots are available in the full version of this review published in the Cochrane Library.1
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Acknowledgments
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Disclosures
None.
Received July 9, 2009;
accepted July 27, 2009.
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Reference
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1. Manktelow BN, Potter JF. Interventions in the management of serum lipids for preventing stroke recurrence.
Cochrane Database Syst Rev. 2009; 3: CD002091.
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Introduction
Objectives