Statin Treatment and Stroke Outcome in the Stroke

Prevention by Aggressive Reduction in Cholesterol Levels

(SPARCL) Trial
Larry B. Goldstein, MD; Pierre Amarenco, MD; Justin Zivin, MD, PhD; Michael Messig, PhD;
Irfan Altafullah, MD; Alfred Callahan, MD; Michael Hennerici, MD, PhD;
Mary J. MacLeod, PhD, MBChB; Henrik Sillesen, MD, DMSc; Richard Zweifler, MD;
K. Michael A. Welch, MB, ChB; on behalf of the SPARCL Investigators

Background and Purpose—Laboratory experiments suggest statins reduce stroke severity and improve outcomes. The
Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial was a placebo-controlled, randomized
trial designed to determine whether treatment with atorvastatin reduces strokes in subjects with recent stroke or transient
ischemic attack (n⫽4731). We analyzed SPARCL trial data to determine whether treatment favorably shifts the
distribution of severities of ischemic cerebrovascular outcomes.
Methods—Severity was assessed with the National Institutes of Health Stroke Scale, Barthel Index, and modified Rankin Scale
score at enrollment (1 to 6 months after the index event) and 90 days poststroke in subjects having a stroke during the trial.
Results—Over 4.9 years, strokes occurred in 576 subjects. There were reductions in fatal, severe (modified Rankin Scale
score 5 or 4), moderate (modified Rankin Scale score 3 or 2), and mild (modified Rankin Scale score 1 or 0) outcome
ischemic strokes and transient ischemic attacks and an increase in the proportion of event-free subjects randomized to
atorvastatin (P⬍0.001 unadjusted and adjusted). Results were similar for all outcome events (ischemic and hemorrhagic,
P⬍0.001 unadjusted and adjusted) with no effect on outcome hemorrhagic stroke severity (P⫽0.174 unadjusted,
P⫽0.218 adjusted). If the analysis is restricted to those having an outcome ischemic stroke (ie, excluding those having
a transient ischemic attack or no event), there was only a trend toward lesser severity with treatment based on the
modified Rankin Scale score (P⫽0.0647) with no difference based on the National Institutes of Health Stroke Scale or
Barthel Index.
Conclusion—The present exploratory analysis suggests that the outcome of recurrent ischemic cerebrovascular events
might be improved among statin users as compared with nonusers. (Stroke. 2009;40:3526-3531.)
Key Words: ICH 䡲 outcome 䡲 statins 䡲 stroke

T he Stroke Prevention with Aggressive Reduction of

Cholesterol Level (SPARCL) trial randomized 4731
subjects who had a stroke or transient ischemic attack (TIA)
within 1 to 6 months before study entry, a low-density
lipoprotein cholesterol (LDL-C) level of 100 to 190 mg/dL,
and no known coronary heart disease to double-blind treatment
with 80 mg atorvastatin per day or placebo.1 The trial’s primary
end point (time to a first fatal or nonfatal stroke) was reduced by
16% in subjects who were randomized to atorvastatin.1
3-hydroxy-3-methylglutaryl coenzyme reductase inhibitors
(statins) such as atorvastatin have a variety of actions in
addition to their lipid-lowering properties that might not only
affect the risk of stroke, but also stroke outcome.2– 4 Results of
studies evaluating the effects of statins on stroke severity and
functional outcome in humans have been inconsistent.5–10
The primary purpose of this exploratory analysis was to
determine whether randomization to statin therapy affected
the outcome of recurrent ischemic strokes in SPARCL
subjects. Additional analyses were conducted to assess the
effect of being randomized to statin treatment on the outcome
of all recurrent strokes (ischemic plus hemorrhagic) and the
outcome of hemorrhagic strokes separately.
Methods
The methods of the SPARCL study have been described in detail
previously.1,11 Briefly, the local research ethics committee or Insti-

Received May 7, 2009; final revision received June 5, 2009; accepted June 25, 2009.
From the Department of Medicine, Division of Neurology, Duke University Medical Center (L.B.G.), Durham, NC; the Department of Neurology,
Denis Diderot University (P.A.), Paris, France; the Department of Neurology, University of California (J.Z.), San Diego, Calif; Pfizer (M.M.), New York,
NY; Minneapolis Clinic of Neurology (I.A.), Golden Valley, Minn; Neurologic Consultants (A.C.), Nashville, Tenn; the Department of Neurology,
University of Heidelberg (M.H.), Mannheim, Germany; the Department of Medicine and Therapeutics, University of Aberdeen (M.J.M.), Aberdeen, UK;
the Department of Vascular Surgery, University of Copenhagen (H.S.), Copenhagen, Denmark; Department of Neurology, Sentara Healthcare and Eastern
Virginia Medical School (R.Z.), Norfolk, Va; and Rosalind Franklin University of Medicine and Science (K.M.A.W.), North Chicago, Ill.
Correspondence to Larry B. Goldstein, MD, Box 3651, Duke University Medical Center, Durham, NC 27710. E-mail golds004@mc.duke.edu
© 2009 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STROKEAHA.109.557330

3526
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 Goldstein et al Statins and Stroke Outcome 3527

tutional Review Board at each center approved the study protocol, Table 1. Stroke Severity at Baseline in Subjects Having an
and all patients gave written informed consent. Eligible patients were Outcome Stroke
⬎18 years of age, had an ischemic or hemorrhagic stroke or a TIA
1 to 6 months before randomization, and had no known coronary Atorvastatin Placebo
heart disease. Subjects had to have a modified Rankin Scale (mRS) (N⫽209) (N⫽246) P
score of no more than 3 (see subsequently) and an LDL-C level of at NIHSS, mean⫾SEM 2.01⫾0.20 2.37⫾0.22 0.2567
least 100 mg/dL and no more than 190 mg/dL (15 of the 205 centers
excluded otherwise suitable patients with an LDL-C level ⬎160 Median⫾IQR 1⫾3 1⫾3 0.6471
mg/dL as required by their Institutional Review Boards). Patients BI, n (%)
with atrial fibrillation, mechanical prosthetic heart valves, severe ⬍60 2 (1%) 2 (1%) 0.5561
mitral valve stenosis, or subarachnoid hemorrhage were excluded.
Patients with hemorrhagic stroke (2% of the study population) could 60 to ⬍95 25 (12%) 25 (10%)
be included if they were deemed by the investigator to be at risk for ⱖ95 186 (87%) 222 (89%)
ischemic stroke or coronary heart disease. Subjects were enrolled
mRS score, n (%)
between September 1998 and March 2001 at 205 centers in 27
countries. An independent committee adjudicated all potential pri- 0 80 (33%) 90 (32%) 0.3731
mary and secondary end points without knowledge of the patients’ 1 101 (42%) 110 (38%)
treatment status or cholesterol levels. The type of outcome stroke
2 36 (15%) 52 (18%)
was not adjudicated.
The severity of the index stroke (ie, at the time of randomiza- 3 23 (9%) 34 (12%)
tion) was assessed with the National Institutes of Health Stroke 4 1 (1%) 0
Scale (NIHSS; neurological impairments),12 Barthel Index (BI;
disability),13 and mRS score (handicap).14 The reliability of the 5 0 0
NIHSS has been established in several studies, and all investigators IQR indicates interquartile range.
were certified in its use.15,16 A score of 0 reflects no measurable
impairment. The BI evaluates independence in activities of daily
living. Pivotal scores correspond to severe dependence (score ⬍40) Probabilities were calculated from analysis of covariance models
and assisted independence (score ⬎60).17 A score of 100 reflects no adjusting for age, gender, and baseline severity for mean NIHSS;
disability. The mRS assesses functional outcome with scores ranging from Wilcoxon tests for median NIHSS; and from Cochran-Mantel-
from 0 to 6 (0, no symptoms; 1, no significant disability despite Haenszel tests with modified RIDIT scores adjusted for age, gender,
symptoms and able to carry out all usual duties and activities; 2, and baseline severity for the BI and mRS.
slight disability, unable to carry out all previous activities but able to
look after own affairs without assistance; 3, moderate disability Results
requiring some help but able to walk without assistance; 4, moderate Details of the characteristics of the SPARCL subject popu-
severe disability, unable to walk without assistance, and unable to
attend to own bodily needs without assistance; 5, severe disability;
lation and the baseline comparability of the groups random-
bedridden, incontinent, and requiring constant nursing care and ized to atorvastatin and placebo have been published (see
attention; and 6, death). These measures were repeated 90 days after referenced report; Table 1).1 Baseline stroke severity data
a recurrent stroke. Because the data come from a secondary preven- were available for 209 atorvastatin-randomized and 246
tion trial, subjects could have been evaluated and treated at a variety placebo-randomized subjects who later had an outcome
of nonstudy sites at the time of the recurrent outcome stroke.
Therefore, obtaining data on initial severity of the recurrent stroke stroke and were similar for the 2 groups (Table 1).
was not possible. Assessors were unaware of the subject’s treatment Over a median follow-up of 4.9 years, 492 subjects had an
group. outcome ischemic stroke (218 in the atorvastatin group versus
The net difference in statin use between groups was 78.1% by the 274 in the placebo group; hazard ratio, 0.79; 95% CI, 0.66 to
end of the trial (versus 100% had all subjects adhered to their
randomized treatment group).1 For the purposes of the present
0.95).19 Baseline characteristics were similar for subjects
analyses, subjects were assigned to their randomized treatment group having an outcome ischemic stroke who were randomized to
regardless of subsequent adherence. We a priori hypothesized that atorvastatin versus placebo (Table 2). The Figure (middle
atorvastatin treatment would favorably shift the distribution of panel) gives the distribution of outcomes for subjects ran-
ischemic outcome events (ie, a shift along a continuum from fatal to domized to atorvastatin (data available for 2291 of 2310
severe, moderate, or mild strokes; TIAs; and no events) based on
mRS scores at 90 days after a first outcome event (mRS 5 or 4, subjects who had an ischemic event or no stroke [99.2%])
severe; mRS 3 or 2, moderate; mRS 1 or 0, mild). Probabilities were versus placebo (data available for 2300 of 2333 subjects
calculated from Cochran-Mantel-Haenszel tests with modified [98.6%]). There are proportional reductions in fatal, severe,
RIDIT scores adjusting for age, gender, and baseline severity. moderate, and mild ischemic strokes and TIAs and an
We performed secondary analyses for all first outcome events
(ischemic and hemorrhagic) and separately for first hemorrhagic
increase in the proportion of event-free subjects randomized
strokes (without TIA as a possible outcome). We also compared the to atorvastatin (P⬍0.001 unadjusted, P⬍0.001 adjusted).
mean and median NIHSS and BI (⬍60, 60 to 95, ⱖ95) for subjects A total of 265 subjects randomized to atorvastatin and 311
surviving a first outcome stroke (ie, excluding those having no randomized to placebo had an outcome ischemic or hemor-
events, TIAs, or fatal events) and the mRS (including mortality) for rhagic stroke.1 The Figure (top panel) gives the distribution of
each type of outcome.
In a prior exploratory analysis, we found that 96% of SPARCL outcomes for subjects randomized to atorvastatin (data avail-
subjects reaching a ⱖ50% decrease in LDL-C from baseline had able for 2334 of 2365 subjects who had an outcome event or
been randomized to atorvastatin.18 In a further secondary analysis, no stroke [98.7%]) versus placebo (data available for 2333 of
we assessed the impact of having a ⱖ50% decrease in LDL-C 2366 subjects [98.6%]). There are proportional reductions in
from baseline at the visit just before an outcome event (or the last
LDL-C for those not having an event) on the distribution of
fatal, severe, moderate, and mild strokes and TIAs and an
outcomes (ie, having an LDL-C reduction ⱖ50% was used as an increase in the proportion of event-free subjects randomized
indicator of statin use). to atorvastatin (P⬍0.001 unadjusted, P⬍0.001 adjusted). The
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3528 Stroke November 2009

Table 2. Baseline Characteristics for Patients Who Had an

Outcome of Ischemic Stroke
Atorvastatin (n⫽218) Placebo (n⫽274)
Age, years 66⫾11 65⫾11
Male, n (%) 141 (65%) 181 (66%)
Systolic blood pressure, 142⫾20 141⫾20
mm Hg
Body mass index, kg/m2 27⫾4.8 27⫾4.2
Current smoker, n (%) 38 (17%) 66 (24%)
Diabetes mellitus, n (%) 51 (23%) 78 (29%)
Entry event, n (%)
Stroke 174 (80%) 219 (80%)
Ischemic 170 (78%) 217 (79%)
Hemorrhagic 3 (1%) 2 (1%)
Other/not determined 1 (⬍1%) 0
TIA 44 (20%) 55 (20%)
Time since entry event, 83⫾53 84⫾48
days
Lipids, mg/dL (mmol/L)
LDL-C 134⫾24.8 (3.5⫾0.6) 134⫾23.8 (3.5⫾0.6)
High-density lipoprotein 48.5⫾12.5 (3.5⫾0.6) 48.0⫾12.3 (1.2⫾0.3)
cholesterol
Total cholesterol 212⫾28.7 (5.5⫾0.7) 211⫾28.2 (5.5⫾0.7)
Triglycerides 147⫾66.6 (1.7⫾0.8) 144⫾63.5 (1.6⫾0.7)
Values are means⫾SD unless otherwise indicated.

results were similar using achievement of a ⱖ50% reduction

in LDL-C from baseline instead of randomization group (data
not shown; P⬍0.039 unadjusted; P⬍0.013 adjusted).
A total of 55 subjects randomized to atorvastatin and 33
randomized to placebo had an outcome hemorrhagic stroke.1
Although the incidence of hemorrhage was higher in
atorvastatin-randomized subjects, there was no difference in
outcome between those randomized to atorvastatin (data
available for 2030 of 2147 subjects who had a hemorrhagic
stroke or no event [94.6%]) versus placebo (data available for
1917 of 2092 subjects [91.6%]; Figure, bottom panel;
P⫽0.218), including no difference in the incidence of fatal
hemorrhagic strokes (17 in the atorvastatin- and 18 in the
placebo-randomized groups). Figure. Incidence and severity of outcome events. Distribution
Table 3 compares the mean and median NIHSS and BI of outcomes for all events (top panel), ischemic events (middle
(⬍60, 60 to 95, ⱖ95) for subjects surviving any outcome panel). and hemorrhagic strokes (bottom panel) 90 days after an
outcome event (mRS 4 or 5, severe; mRS 2 or 3, moderate;
stroke, ischemic stroke, or hemorrhagic stroke (ie, excluding mRS 0 or 1, mild).
those having no events, TIAs, or fatal events) and the mRS
(including mortality) for each type of outcome. Although statin on the occurrence of strokes in subjects with a prior
there was a trend toward lesser severity with atorvastatin stroke or TIA, however, it provides a unique opportunity for
treatment based on the mRS in subjects having an outcome an assessment of the potential effects of these drugs on the
ischemic stroke (P⫽0.0647), none of the differences were entire range of possible stroke outcomes (ie, a shift along a
significant. continuum from fatal to severe, moderate, or mild strokes;
TIAs; and no events). The primary finding of this analysis
Discussion was that SPARCL subjects randomized to atorvastatin had a
We found only a trend favoring a reduction in the severity of favorable shift in the distribution of outcome ischemic events
outcome ischemic strokes with statin treatment based on the assessed after 90 days as compared with those randomized to
categorized mRS with no difference based on the NIHSS or placebo (Figure, middle panel). The results were similar for
BI. Because this analysis was based on data collected as part all outcome events (Figure, top panel) and when using
of a prospective, randomized trial assessing the impact of a achievement of a 50% or greater reduction in LDL-C from
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 Goldstein et al Statins and Stroke Outcome 3529

Table 3. Stroke Severity 90 Days After an Outcome Stroke baseline at the last assessment before an outcome event as an
Atorvastatin Placebo P
index of stain adherence.
Observational clinical studies also provide data reflecting
All strokes
the potential impact of statins on ischemic stroke severity and
NIHSS, mean⫾SEM 3.71⫾0.36 4.27⫾0.33 0.2433 outcome, although the results have been inconsistent. Most
Median⫾IQR 2⫾6 2⫾6.5 0.7296 evaluated the effects of statins taken before the index stroke
(N⫽209) (N⫽246) and found no clear impact on initial severity.6,7,9 One study
BI, n (%) reported a reduction in mortality among statin users 1 month
⬍60 26 (12%) 35 (14%) 0.4408 after ischemic stroke and over a mean follow-up period of 2.4
60 to ⬍95 42 (20%) 45 (18%)
years but did not assess severity.8 Another found a reduction
in stroke progression,7 a result not found in a second.5 Two of
ⱖ95 145 (68%) 169 (68%)
the studies found some improvement in functional out-
mRS score, n (%)
come,5,6 at least for some measures, whereas another did not.7
0 35 (15%) 42 (15%) 0.4531 A third found that statin pretreatment was associated with
1 73 (30%) 84 (29%) better neurological outcomes in whites but not blacks.10 One
2 45 (18%) 46 (16%) of the studies also evaluated the impact of poststroke statins
3 35 (15%) 42 (15%) on the outcome after a second stroke, finding a functional
4 24 (10%) 26 (9%) benefit assessed after 12 weeks.6 These studies were neces-
5 7 (3%) 14 (5%)
sarily constrained by their retrospective designs. The subjects
took different types of statins at varying doses both within
6 22 (9%) 32 (11%)
and between studies. This variability and other design issues
Ischemic strokes
may underlay the disparate results. In SPARCL, all statin-
NIHSS, mean⫾SEM 3.49⫾0.36 4.21⫾0.32 0.1257 treated patients were randomized to receive a single statin at
Median⫾IQR 2⫾5 2⫾6 0.3203 a single dose thereby limiting one source of variability. In
(N⫽180) (N⫽232) addition, the previous studies could not evaluate the potential
BI, n (%) impact of statins on the entire continuum of outcomes
⬍60 18 (10%) 32 (14%) 0.0973 because they could not account for subjects receiving statins
60 to ⬍95 33 (18%) 43 (18%)
who had outcome TIAs or no events. As noted, we found no
significant effect of being randomized to statin treatment on
ⱖ95 133 (72%) 160 (68%)
stroke-related impairments, disabilities, or handicaps if the
mRS score, n (%)
analysis was restricted to those having an outcome stroke
0 33 (18%) 39 (15%) 0.0647 (Table 3).
1 66 (33%) 80 (31%) This analysis was primarily aimed at assessing the poten-
2 42 (21%) 42 (16%) tial effect of statin therapy on the outcomes of ischemic
3 28 (14%) 42 (16%) events, but a secondary analysis was conducted for outcome
4 15 (8%) 25 (10%) hemorrhagic strokes. Experimentally, statin administration
5 5 (2%) 12 (5%)
after intracerebral hemorrhage reduces acute inflammation
and improves neurological outcome.20,21 A retrospective
6 8 (4%) 17 (7%)
study found that prior statin use was associated with reduced
Hemorrhagic strokes
perihematomal edema and improved survival in a series of
NIHSS, mean⫾SEM 4.52⫾1.62 5.59⫾2.21 0.6827 patients with nontraumatic intracerebral hemorrhage.22,23
Median⫾IQR 4⫾6 2⫾8 0.3204 Analysis of SPARCL data found that statin treatment was
(N⫽29) (N⫽14) associated with an increased risk of hemorrhagic stroke in
BI, n (%) subjects with prior stroke that was independent of other
⬍60 8 (28%) 3 (22%) 0.4954 factors.1,19 Although limited by small numbers and therefore
60 to ⬍95 9 (31%) 2 (14%)
low statistical power, the current analysis found no difference
in the outcomes of hemorrhagic strokes (Figure, bottom
ⱖ95 12 (41%) 9 (64%)
panel). Similarly, a retrospective analysis of 90-day outcome
mRS score, n (%) data from 629 consecutive patients from a single-center
0 2 (5%) 3 (10%) 0.4716 longitudinal cohort study of primary intracerebral hemor-
1 7 (16%) 4 (14%) rhage found no effect of prior statin use on functional
2 3 (6%) 4 (14%) independence or mortality.24 We found that the overall
3 7 (16%) 0 benefit of randomization to atorvastatin on outcome was
4 9 (20%) 1 (3%) maintained if the analysis was carried out for all events (ie,
ischemic and hemorrhagic events; Figure, top panel).
5 2 (5%) 2 (7%)
If statin treatment does reduce ischemic stroke severity, the
6 14 (32%) 15 (52%)
effect is unlikely to be related to the potent lipid-lowering
IQR indicates interquartile range. properties of these drugs. Statins have anti-inflammatory,
antithrombotic, and vasoactive effects as well as other actions
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3530 Stroke November 2009
that might be neuroprotective or affect infarct size, leading to
a reduction in the severity of the acute stroke. For example, 2
to 4 days of statin pretreatment protects against glutamate
excitotoxicity in primary cortical neuronal cell cultures,
independent of the drug’s effects on 3-hydroxy-3-
methylglutaryl coenzyme reductase.25 Induction of heat
shock proteins enhances survival of axotomized retinal gan-
glion cells.26 Statins reduce superoxide production and
stroke-associated infiltration of inflammatory cells in stroke-
prone spontaneously hypertensive mice.27 Statins inhibit nu-
clear factor ␬B activity and cytokine gene expression thereby
potentially reducing the poststroke inflammatory response.28
Abrupt termination of statin administration results in rapid
loss of protection in mouse models of cerebral ischemia
further suggesting that the protective effect is independent of
cholesterol-lowering.29 Statin pretreatment also upregulates
endothelial nitric oxide synthase, increases cerebral blood
flow, reduces infarct size, and improves neurological out-
come without affecting serum cholesterol levels in mice
subjected to experimental stroke, effects absent in endothelial
nitric oxide synthase-deficient mice.30 Statin-related upregu-
lation of endothelial nitric oxide synthase also reduces plate-
let activation independent of the drug’s lipid-lowering prop-
erties.31 Furthermore, pre-exposure to statins upregulates
endogenous tissue plasminogen activator and enhances clot
lysis after experimental embolic stroke.32 In addition, statins
promote angiogenesis, potentially improving blood supply to
ischemic tissue.4,33 Interestingly, preischemic stroke statin
users have more extensive arterial collaterals than nonstatin
users.34 More extensive arterial collaterals might also be
expected to lead to lower stroke severity, although a func-
tional benefit was not found in this observational study.
Despite these effects, as noted previously, none of the
observational clinical studies have found lower initial ische-
mic stroke severity among prestroke statin users as compared
with nonusers.
In addition to their potential effects in decreasing initial
stroke severity, statins might also affect the brain’s response
to injury. Statins induce poststroke neurogenesis in laboratory
animals.4 They also increase neurogenesis in the dentate
gyrus, reduce delayed neuronal death, and improve spatial
learning in rats after traumatic brain injury.35 Our study
measured functional outcome 90 days after an outcome
stroke. Data reflecting stroke severity within the first days
after the outcome stroke were not available. Therefore, it is
not possible to determine to what degree an effect of
treatment on overall outcome in SPARCL subjects might be
due to a reduction in acute stroke severity related to “neuro-
protective” properties, enhanced poststroke recovery, or a
combination of the 2 effects.
This analysis has several limitations. As noted, not all
subjects adhered to their randomized treatments, but the
results were not substantially different using LDL-C reduc-
tion as an indicator of statin use. We did not have data for the
subject’s socioeconomic status, immediate poststroke com-
plications, detailed cognitive function, family support, insur-
ance status, duration of hospitalization, or poststroke rehabil-
itation, so we could not adjust for these factors, which can
affect poststroke functional outcome. The analysis was,
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however, based on a subjects enrolled in a prospective trial
who were randomized to one of 2 groups (ie, statin treatment
versus placebo), the independent variable for this analysis.
The 2 groups were otherwise comparable (prior publication
Table 1,1 current report; Tables 1 and 2), and there is no
reason to suspect that they would differ for other character-
istics that might affect outcome. Although the primary
hypothesis and statistical plan for this analysis were deter-
mined a priori, SPARCL was not primarily designed to assess
the effects of atorvastatin on stroke severity, and this study
should be viewed as exploratory.
The primary results of the SPARCL trial showed that
treatment with atorvastatin reduced the rate of recurrent
stroke in patients with recent stroke or TIA. The present
exploratory analysis needs to be interpreted with caution but
suggests that the outcome of recurrent ischemic cerebrovas-
cular events may be improved among statin users as com-
pared with nonusers if the full range of possible outcomes is
considered. There is, however, only a nonsignificant trend
favoring functional improvement (based on the mRS) if the
analysis is limited to those who have a second stroke.
Source of Funding
The SPARCL trial was funded by Pfizer. Employees of Pfizer
contributed to the design and conduct of the SPARCL trial; the
collection, management, analysis, and interpretation of the data; and
reviewed the manuscript.
Disclosures
L.B.G. received honoraria from Pfizer during the course of this study
and has served as a consultant for Pfizer. The honoraria and
consulting fees did not exceed $10 000/year. P.A. has received grants
from Pfizer for other research or activities not reported in this
research exceeding $10 000/year and honoraria from Pfizer in excess
of $10 000/year during the course of this study. J.Z. received
honoraria from Pfizer during the course of this study and has served
as a consultant for Pfizer. The honoraria and consulting fees did not
exceed $10 000/year. M.M. is an employee of Pfizer and owns Pfizer
stock. I.A. served as a site investigator in the SPARCL trial. He owns
Pfizer stock and has received honoraria from Pfizer. The amount of
honoraria and all other income from Pfizer is less than $10 000/year.
A.C. has received research support and honoraria from Pfizer in
excess of $10 000/year during the course of this study. M.H. has
received grants from Pfizer for other research or activities not
reported in this research/article and honoraria from Pfizer during the
course of the study. Neither the grants nor the honoraria exceeded
$10 000/year. M.J.M. served as a site investigator in the SPARCL
trial. She has received honoraria totaling less than $1000 from Pfizer.
H.S. has received grants from Pfizer for other research or activities
not reported in this research/article in excess of $10 000/year and
honoraria exceeding $10 000/year during the course of this study.
K.M.A.W. received honoraria from Pfizer during the course of this
study and has served as a consultant for Pfizer in excess of
$10 000/year.
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Statin Treatment and Stroke Outcome in the Stroke Prevention by Aggressive Reduction
in Cholesterol Levels (SPARCL) Trial
Larry B. Goldstein, Pierre Amarenco, Justin Zivin, Michael Messig, Irfan Altafullah, Alfred
Callahan, Michael Hennerici, Mary J. MacLeod, Henrik Sillesen, Richard Zweifler, K. Michael
and A. Welch
on behalf of the SPARCL Investigators

Stroke. 2009;40:3526-3531; originally published online September 10, 2009;

doi: 10.1161/STROKEAHA.109.557330
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
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