Relationship between risk factor control
and vascular events in the SAMMPRIS trial

Tanya N. Turan, MD
Azhar Nizam, MS
Michael J. Lynn, MS
Brent M. Egan, MD
Ngoc-Anh Le, PhD
Maria F. Lopes-Virella,
MD, PhD
Kathie L. Hermayer, MD
Jamie Harrell, BS
Colin P. Derdeyn, MD
David Fiorella, MD
L. Scott Janis, PhD
Bethany Lane, MSN
Jean Montgomery, RN
Marc I. Chimowitz,
MBChB

ABSTRACT

Objective: The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in
Intracranial Stenosis (SAMMPRIS) study is the first stroke prevention trial to include protocoldriven intensive management of multiple risk factors. In this prespecified analysis, we aimed toinvestigate the relationship between risk factor control during follow-up and outcome of patientsin the medical arm of SAMMPRIS.

Methods: Data from SAMMPRIS participants in the medical arm (n 5 227) were analyzed. Risk
factors were recorded at baseline, 30 days, 4 months, and then every 4 months for a mean followup of 32 months. For each patient, values for all risk factor measures were averaged and dichotomized as in or out of target.

Results: Participants who were out of target for systolic blood pressure and physical activity, as
well as those with higher mean low-density lipoprotein cholesterol and non–high-density lipoprotein, were more likely to have a recurrent vascular event (stroke, myocardial infarction, or vasculardeath) at 3 years compared to those who had good risk factor control. In the multivariable analysis, greater physical activity decreased the likelihood of a recurrent stroke, myocardial infarction, or vascular death (odds ratio 0.6, confidence interval 0.4–0.8).

Conclusions: Raised blood pressure, cholesterol, and physical inactivity should be aggressively
Correspondence toDr. Turan:turan@musc.edu

treated in patients with intracranial atherosclerosis to prevent future vascular events. Physicalactivity, which has not received attention in stroke prevention trials, was the strongest predictorof a good outcome in the medical arm in SAMMPRIS.

ClinicalTrials.gov identifier: NCT00576693. Neurology® 2017;88:379–385
GLOSSARYBMI 5 body mass index; BP 5 blood pressure; CI 5 confidence interval; HbA1c 5 hemoglobin A1c; HDL-C 5 high-density
lipoprotein cholesterol; ICAS 5 intracranial atherosclerotic stenosis; LDL-C 5 low-density lipoprotein cholesterol; MI 5
myocardial infarction; mRS 5 modified Rankin Scale score; NIHSS 5 NIH Stroke Scale; OR 5 odds ratio; PACE 5 Physician-based Assessment and Counseling for Exercise; SAMMPRIS 5 Stenting and Aggressive Medical Management for
Prevention of Recurrent Stroke in Intracranial Stenosis; SBP 5 systolic blood pressure; WASID 5 Warfarin Aspirin Symptomatic Intracranial Disease.

Editorial, page 342

Intracranial atherosclerotic stenosis (ICAS) is an important cause of stroke worldwide1 that is
associated with a particularly high risk of recurrent stroke.2,3 Post hoc analyses from the Warfarin
Aspirin Symptomatic Intracranial Disease (WASID) trial, in which patients with symptomatic
50%–99% intracranial stenosis were treated with standard of care risk factor management andrandomized to either warfarin or aspirin, suggested that poorly controlled blood pressure (BP)4and elevated cholesterol5 during follow-up are important risk factors for recurrent stroke andother vascular events. These findings led to the incorporation of intensive risk factor management in the design of the Stenting and Aggressive Medical Management for Prevention of
Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial.6 The final results of SAMMPRIS
showed that multimodal aggressive medical management alone was superior to the combinationof angioplasty and stenting plus aggressive medical management in patients with severe ICAS.7

Supplemental data
at Neurology.org
From Medical University of South Carolina (T.N.T., M.F.L.-V., K.L.H., J.H., M.I.C.), Charleston; Emory University (A.N., M.J.L., B.L., J.M.),
Atlanta, GA; University of South Carolina School of Medicine (B.M.E.), Greenville; Atlanta VAMC (N.-A.L.), Decatur, GA; Washington
University (C.P.D.), St. Louis, MI; State University of New York at Stony Brook (D.F.); and National Institute of Neurological Disorders andStroke (L.S.J.), Bethesda, MD.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
© 2016 American Academy of Neurology379ª 2016 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

Table 1

Stenting and Aggressive Medical Management for Prevention of
Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) risk factor
targets and control during follow-up

Risk factor
measureTargetNo. patients withavailable data

Percentage ofpatients in target
overalla

Primary risk
factors
Systolic bloodpressure,140 mm Hg (,130 if
diabetic)

227

53

LDL-C

,70 mg/dL

225

47,100 mg/dL

225

60

Secondary risk
factors
Non-HDL-C
b

HbA1c

,7.0%

113

42

Smoking

Cessation

227

65

Weightmanagement

For initial BMIc of 25–27
kg/m2: target BMI ,25
kg/m2; forinitial BMI .27 kg/m2:
target 10% weight loss

227

19

Physical activity

PACE score of 4–8d

227

44

Abbreviations: BMI 5 body mass index; HbA1c 5 hemoglobin A1c; HDL-C 5 high-density
lipoprotein cholesterol; LDL-C 5 low-density lipoprotein cholesterol; PACE 5 Physicianbased Assessment and Counseling for Exercise.
aValues from baseline until the time of the adverse event (for patients with an event) or
close-out (for patients without an event) were averaged for each risk factor anddichotomized as in target or out of target.
b
Diabetic patients only.
c
BMI 5 (weight in pounds/[height in inches 3 height in inches]) 3 703.
d
See appendix e-1 for details of PACE score, ranging from moderate exercise less than 5times per week or vigorous exercise less than 3 times per week (PACE score of 4) to at least
20 minutes of vigorous exercise at least 3 days a week for the past 6 months or more
(PACE score of 8).

A prespecified analysis of the SAMMPRIS trial
was to investigate the relationship between
control of risk factors achieved with intensive
risk factor management protocols and outcome of patients in the medical arm of thetrial. We now report the results of this analysis.
METHODS Standard protocol approvals, registrations,and patient consents. The SAMMPRIS protocol was approvedby the site institutional review boards, US Food and Drug Administration, and Data and Safety Monitoring Board appointed by the
NIH. Informed consent was obtained from each participant.
ClinicalTrials.gov identifier: NCT00576693.

Trial design. The overall design of SAMMPRIS has been
described previously.8 In brief, SAMMPRIS was an NIH-funded,
investigator-initiated and designed phase III randomized trial inwhich 451 patients were randomized at 50 sites in the UnitedStates to aggressive medical therapy alone or percutaneoustransluminal angioplasty and stenting (with the Wingspan stentsystem) plus aggressive medical therapy. The main eligibility
criteria were TIA or nondisabling stroke within 30 days caused
by 70%–99% stenosis of a major intracranial artery (middle
cerebral artery, carotid, vertebral, or basilar).
The primary outcomes in SAMMPRIS were any stroke ordeath within 30 days after enrollment, any stroke or death within
30 days after a revascularization procedure of the qualifying lesion
380

Neurology 88

during follow-up, and ischemic stroke in the territory of the qualifying artery beyond 30 days. The combination of any ischemic
stroke, myocardial infarction (MI), or vascular death was a secondary outcome in SAMMPRIS, but is the primary outcome in thisprespecified analysis because intensive risk factor control affects
all of these important vascular events. Details regarding the adjudication of adverse events (ischemic stroke, MI, vascular death)are described elsewhere.8 In brief, study neurologists who were
not masked to treatment assignment evaluated patients witha potential adverse event as soon as possible after the event.
Patients with neurologic events that were potentially difficult toclassify (a TIA lasting .1 hour or mild ischemic stroke [anincrease in the patient’s NIH Stroke Scale score of ,4 from study
entry]) were evaluated by a second neurologist who was masked
to treatment. Both neurologists’ assessments were sent for central
adjudication. All adverse events (neurologic or cardiac) were centrally adjudicated by neurology or cardiology adjudicators who
were masked to treatment assignment.

Aggressive medical management. Details of the rationale,
design, implementation, baseline risk factor control, and achievement of risk factor control in SAMMPRIS have been described
previously.6,7 In brief, aggressive medical therapy consisted of aspirin 325 mg/d during the entire follow-up period (mean follow-up
of approximately 32 months), clopidogrel 75 mg/d for 90 days
after enrollment, and aggressive risk factor management primarily
targeting systolic BP (SBP) ,140 mm Hg (,130 if diabetic) andlow-density lipoprotein cholesterol (LDL-C) ,70 mg/dL. The
protocol-defined primary and secondary risk factor targets arelisted in table 1. Risk factor management was performed by thestudy neurologist and coordinator at each site. The following
strategies were used to maximize attainment of risk factor
targets: providing study medications to patients free of charge,
employing medication titration algorithms for primary risk
factors, and central oversight of risk factor performance. All
participants also received coaching on healthy lifestyle behaviors
at regularly scheduled times throughout the study using
a commercially available lifestyle modification program(INTERVENT) at no charge.
Collection of risk factor data. Data from each patient visit
throughout the study until the end of year 3 were used to analyze
the relationship between risk factor control and vascular events.
The accuracy of the SBP measurements was standardized byrequiring the use of a highly rated BP monitoring device (Omron
HEM-705CP; Omron, Kyoto, Japan) at all sites. The study
protocol required the participants to be in the sitting position
and the study device to be used with a printout of the BP
readings for source documentation. At the baseline visit, 3 BP
measurements were averaged and recorded as the initial
measurements for each arm. All subsequent BP measurements
were done in a selected arm. The right arm was considered theselected arm unless the left arm mean SBP measured .10 mm Hg
higher than the right arm at the initial measurement. At each visit,
3 BP measurements were averaged to determine the mean BP for that
visit. The frequency of BP data collection depended on theachievement of the SBP target. At any follow-up visit throughout
the study, if a patient’s mean SBP was above target, an adjustment in
the antihypertensive regimen was made, and the patient returned foran extra BP check in 30 days. Once the target BP reading wasreached, the patient resumed the normal schedule of follow-up
visits every 4 months.
The accuracy of the baseline, 30 days, and 4 months LDL-C
and non–high-density lipoprotein cholesterol (HDL-C) measurements was standardized by using a central core lipid

January 24, 2017ª 2016 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

Table 2

Risk factors associated with stroke, myocardial infarction, or vasculardeath at 3 years
Odds ratio (95% CI)

Risk factor

Multivariablea

Univariate

Physical activityb
Out of target

5.4 (2.4–12.1)cContinuous (mean PACE score)

0.5 (0.4–0.7)c

0.6 (0.4–0.8)cLDL
Out of target

1.8 (1.0–3.6)

Continuous (mean, increase 10 mg/dL)

1.2 (1.1–1.4)c

1.1 (0.8–1.4)

SBP
Out of target

2.1 (1.2–4.0)cContinuous (mean, increase 10 mm Hg)

1.3 (1.1–1.7)c

1.2 (0.9–1.5)

Smoking
Out of target (smoked during study period)

1.6 (0.8–3.2)

dNon-HDLOut of target

1.7 (0.9–3.2)

Continuous (mean, increase 10 mg/dL)

1.2 (1.1–1.3)c

1.1 (0.8–1.4)

e

BMI

Out of target

0.9 (0.4–2.0)

HbA1cf
Out of target

2.0 (0.99–4.1)

Abbreviations: BMI 5 body mass index; CI 5 confidence interval; HbA1c 5 hemoglobin A1c;
HDL 5 high-density lipoprotein; LDL 5 low-density lipoprotein; PACE 5 Physician-based
Assessment and Counseling for Exercise; SBP 5 systolic blood pressure.
aRisk factors significant in univariate analyses were included in the multivariable regression
model.
bDefined by a PACE score of ,4 (see appendix e-1 for score details).
c
Significant at a 5 0.05.
d
Non-HDL 5 total cholesterol minus HDL cholesterol or the sum of LDL plus very-lowdensity lipoprotein.
e
BMI 5 (weight in pounds/[height in inches 3 height in inches]) 3 703.
f
Diabetic patients only.

laboratory. Patient blood samples were sent to the Emory Lipid
Research Laboratory (Atlanta, GA) for measurement of direct
LDL-C. Beyond 4 months, LDL-C (direct or calculated) andnon-HDL-C were collected annually and were measured at theindividual sites. Participants were not required to fast prior toblood sample collection, but fasting status was recorded. Adjustments were made to the lipid-lowering medications based on the
LDL-C results.
Physical activity was assessed using the 8-point Physicianbased Assessment and Counseling for Exercise (PACE) questionnaire, which the participants completed at each visit.6,9,10
Moderate exercise included activities like brisk walking or slow
cycling for at least 10 minutes at a time. Vigorous exercise
included activities like jogging or fast cycling for at least 20 minutes at a time. Physical activity out of target for this study wasdefined as a PACE score of #3 (3 5 trying to do vigorous ormoderate exercise but not exercising regularly, 2 5 no vigorous ormoderate exercise but thinking of starting in next 6 months, and1 5 no vigorous or moderate exercise and no intention to start innext 6 months). Examples of physical activity in target (PACE$4) were as follows: PACE 4 5 moderate exercise ,5 times per
week or vigorous exercise ,3 times per week and PACE 6 5 atleast 30 minutes of moderate exercise a day for at least 5 daysa week for the past 6 months or more. See appendix e-1 at
Neurology.org for full PACE score.
Smoking and body mass index (BMI) were recorded at all
study visits. The protocol recommended testing hemoglobin
A1c (HbA1c) in diabetic patients every 6 months in patients withglycemic control in target and quarterly in patients who were outof target. All additional lipid and HbA1c studies performed
between scheduled visits, BP measurements performed at extra
BP visits, and risk factor results at closeout visits were includedin this analysis.

Statistical analysis. Only data from patients in the medical armof SAMMPRIS were included in this analysis because the relationship between risk factor control and outcome in the stenting arm
was unlikely to be meaningful since most of the strokes in thestenting arm occurred soon after enrollment in the periprocedural
period before risk factors had been optimally controlled. For eachpatient in the medical arm, values from baseline until the time ofthe vascular event (for patients having these events), the time ofclose-out, or 3 years of follow-up (if no events) were averaged foreach risk factor and dichotomized as in target or out of target.
Mean risk factor values were also analyzed as continuous variables.
Binary logistic regressions were performed with the combination of any ischemic stroke, MI, or vascular death as the outcome.
Single-predictor (univariate) regression results were used to selectrisk factors for inclusion in a multivariable model. The analyses
were repeated with ischemic stroke alone as the outcome.
In order to assess the effect of age, sex, stroke disability, baseline BMI, and cardiovascular health at baseline on the patients’ability to exercise and thereby potentially confound the outcome,we compared the unadjusted odds ratio (OR) for physical inactivity with the OR adjusted for these covariates: age, sex, NIH
Stroke Scale (NIHSS), modified Rankin Scale score (mRS), baseline BMI, and cardiovascular disease at baseline (prior MI,
angina, coronary angioplasty or stenting, deep vein thrombosis,
pulmonary embolus, cardiac valve abnormality, congestive heart
failure) and peripheral vascular disease. The OR for physicalactivity was also stratified by physical activity status at baseline.
RESULTS Patients and risk factors. Data from 227 patients in the aggressive medical management only arm
enrolled in the trial were used for these analyses. The
number of events (stroke, MI, and vascular death)was 49, including 32 ischemic strokes. The median(and 25th and 75th percentiles) of the number of risk
factor values per patient were as follows: SBP: 11 (6,15), LDL-C: 6 (4, 8), physical activity: 9 (4, 12),smoking: 9 (4, 12), non-HDL-C: 6 (4, 8), HbA1c:
4 (2, 6), BMI: 10 (4, 12). Two patients were
missing data from the lipid panel. The percentagesof patients with mean risk factor values in target on
average during the trial (including baseline andfollow-up visits) are shown in table 1. With respect
to the primary risk factor targets, 53% of patients hada mean SBP that was in target (,140 mm Hg) during
their participation in the study and 47% had a mean
LDL-C that was in target (,70 mg/dL).

Univariate analyses. The relationships between control
of individual risk factors and various vascular events
for patients in the medical arm are shown in tables
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ª 2016 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

2 and 3. For the primary endpoint of ischemic stroke,MI, or vascular death at 3 years (table 2), participants
who were in target for SBP and physical activity weresignificantly less likely to have an event compared tothose who did not achieve those targets. Lower LDL
and non-HDL were also associated with lower
likelihood of vascular events at 3 years whenanalyzed as continuous variables. For the endpointof ischemic stroke alone (table 3), physical activity
was the only risk factor associated with lower
events. Control of other risk factors (HbA1c,
smoking, and BMI) did not have a significant effecton any of the vascular outcomes assessed.
Multivariable analyses. In multivariable analyses that
included just those risk factors significant in the univariate analyses, greater physical activity on a continuous scale (higher PACE score) decreased thelikelihood of a recurrent stroke, MI, or vascular death(OR 0.6, confidence interval [CI] 0.4–0.8), demonstrating a dose effect of exercise (figure). BP and cholesterol were not significant factors.

Table 3

Risk factors associated with ischemic stroke alone at 3 years
Odds ratio (95% CI)a

Risk factor
Physical activityb
Out of target

6.7 (2.5–18.1)cContinuous (mean PACE score)

0.5 (0.4–0.7)cLDL
Out of target

1.7 (0.8–3.5)

Continuous (mean, increase 10 mg/dL)

1.1 (1.0–1.3)

SBP
Out of target

1.6 (0.8–3.2)

Continuous (mean, increase 10 mm Hg)

1.2 (1.0–1.6)

Smoking
Out of target (smoked during study period)

0.5 (0.3–1.3)

dNon-HDLOut of target

1.4 (0.7–2.9)

Continuous (mean, increase 10 mg/dL)

1.1 (1.0–1.2)e

BMI

Out of target

0.9 (0.4–2.1)

HbA1cf
Out of target

2.3 (1.0–5.0)

Abbreviations: BMI 5 body mass index; CI 5 confidence interval; HbA1c 5 hemoglobin A1c;
HDL 5 high-density lipoprotein; LDL 5 low-density lipoprotein; PACE 5 Physician-based
Assessment and Counseling for Exercise; SBP 5 systolic blood pressure.
a
No multivariable regression was performed, as physical activity was the only significant
factor.
b
Defined by a PACE score of ,4 (see appendix e-1 for score details).
c
Significant at a 5 0.05.
d
Non-HDL 5 total cholesterol minus HDL cholesterol or the sum of LDL plus very-lowdensity lipoprotein.
e
BMI 5 (weight in pounds/[height in inches 3 height in inches]) 3 703.
f
Diabetic patients only.
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Neurology 88

For both the primary endpoint of ischemic stroke,MI, or vascular death and the endpoint of ischemic
stroke alone, the unadjusted OR for physical activity(measured on a continuous scale) and the ORs
adjusted for age, sex, NIHSS, mRS, baseline BMI,
cardiovascular disease, or peripheral vascular disease
were 0.5–0.6, suggesting that the association of physical inactivity and events was not confounded bythese factors. The ORs for physical activity weresimilar for participants who were in target (0.6, CI
0.3–1.0) vs out of target (0.5, CI 0.3–0.7) at baseline.
DISCUSSION This prespecified post hoc analysis of
the relationship between risk factor control and outcome in the medical arm of SAMMPRIS demonstrates that physical activity and intensive control of
BP and cholesterol are important for reducing vascular events in medically treated patients with severe
ICAS. While all 3 of these factors may contributeto the risk of vascular events, the independent effectof physical activity was stronger for the predictionof vascular events than BP and cholesterol.
Remarkably, patients in the medical arm who were
physically inactive had up to 5 times the likelihood of
having a stroke, MI, or vascular death, as well as 6times the risk of any ischemic stroke compared tophysically active patients. In addition, there appears
to be a dose effect of exercise, with higher rates ofactivity having a more protective effect. Previous
meta-analyses have shown that exercise decreases
mortality among stroke patients11 and that physicalactivity decreases the risk of incident stroke among
healthy persons,12 but this analysis now demonstrates
the benefits of physical activity for prevention ofrecurrent ischemic stroke.
Physical inactivity is highly prevalent after stroke
due to factors such as fatigue, poststroke disability,and depression.13 In SAMMPRIS, patients wereenrolled after having a TIA or stroke within the previous 30 days, so it is not surprising that the percentage of patients who were in target for physical activity
at study entry was low (32%). However, at the
4-month follow-up visit, this number had increased
to 56%.14,15 This increase was largely due to compliance with the lifestyle modification program provided
in the trial, which also contributed to the high percentage of patients achieving other risk factor targets.16 Indeed, education and motivation are criticalto enlisting stroke patients in an exercise program,and physicians typically lack the time to provide thelevel of support needed. Comprehensive lifestyle riskreduction programs have been highlighted as an effective way to bridge the gap between recommendations
for physical activity in guidelines and implementationof physical activity in practice,13 and our results support the effectiveness of such an approach.

January 24, 2017ª 2016 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

FigureFitted logistic regression of combined endpoint (stroke, myocardial infarction, or vascular death)
predicted by physical activity (Physician-based Assessment and Counseling for Exercise [PACE]
score) averaged from baseline until the first event or end of follow-up

Maximum follow-up was 3 years. The blue shaded band represents 95% confidence intervals for the probability of theevent. The markers represent the observed data.

The association of poor BP and cholesterol control
with recurrent vascular events in medically treated patients in SAMMPRIS confirms the same findings inthe WASID trial,4,5 which together provide strong
evidence that control of these 2 risk factors is very
important for lowering the risk of vascular events inpatients with ICAS. This analysis also demonstrates
that intensive lowering of BP early after a recent
stroke or TIA appears to be safe in high-risk patientswith ICAS. In WASID, patients were randomized
within 90 days of a stroke or TIA (median time from
qualifying event to enrollment was 17 days) and had
their first follow-up visit at 4 months. Limited conclusions could be drawn about the safety of earlylowering of BP in WASID4,5 because treatment of
BP was not intensive and, in many cases, was delayed
because of the extended time between qualifying
event and enrollment. In contrast, SAMMPRIS patients were enrolled within 30 days of the qualifying
event (median time to enrollment of 7 days), werestarted on intensive BP control at enrollment, andhad their first follow-up visit in 30 days. Given theearlier time from qualifying event to enrollment in
SAMMPRIS, one could hypothesize that SAMMPRIS
patients were less hemodynamically stable than
WASID patients and, therefore, more susceptible toischemia distal to the stenotic artery from intensive
lowering of BP after enrollment. However, this was
not found to be the case in SAMMPRIS as the rate ofvascular events was lower among patients with controlled SBP. Furthermore, this lower event rate
among patients who are in target for SBP is not likely
driven solely by patients who were already in target atbaseline, given that within the first 30 days the percentage of patients achieving SBP target increased
from 33.8% at baseline to 47.6% at 30 days.15
We were unable to demonstrate that control ofsome of the secondary risk factors (e.g., diabetes,
weight, and smoking) significantly reduced recurrent
vascular events in these analyses. This finding is similar to analyses from WASID that failed to show a relationship between control of diabetes and smoking
with outcome.5 However, in both WASID and
SAMMPRIS, patients with better diabetes control
had lower rates of events than patients with poorer
control, but the differences were not statistically significant. The inability of these analyses to demonstrate a benefit of control of the secondary risk
factors targets may be due to a true lack of benefit,
but could also be due to a lack of power to detect aneffect given the small number of patients in somegroups (i.e., type II error).
Our study has some limitations. The risk factor
values were averaged over the duration of follow-up,
which may have diluted the effect of particularly highor low levels that could have been temporally associated with an event (e.g., a particularly high BP that
immediately preceded a stroke). However, the goal
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ª 2016 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

of this analysis was to assess the effect of overall risk
factor control on outcome, not the effect of individualfluctuations in risk factors. While any methodologic
approach to determining the relationship between risk
factors and vascular events has limitations, we chosea measure that takes into account the long-term pathophysiology of atherosclerosis. In addition, since prioranalyses of the relationship between risk factor control
and outcome in patients with stroke due to large arterydisease averaged risk factors over follow-up,4,17 thismethod was used for comparison purposes. Other
possible risk factor interventions, such as dietary modification, were not analyzed, so their effect cannot be
addressed in this study. Another limitation is that thiswas a post hoc analysis (albeit prespecified) and nota randomized trial of different risk factor treatment
targets. Therefore, we cannot rule out the effect of
unknown confounders on our results. However, giventhat the effect of BP and cholesterol control in
SAMMPRIS is consistent with findings from WASID,
the findings appear to be reliable.
Well-controlled BP, cholesterol, and physicalactivity during follow-up were associated with fewer
vascular events in SAMMPRIS. These findings support treatment of elevated BP, cholesterol, andphysical inactivity in patients with intracranial atherosclerosis to prevent future vascular events.
AUTHOR CONTRIBUTIONS
T. Turan: study concept and design, drafting the manuscript, study
supervision A. Nizam: analysis and interpretation of the data. M. Lynn:
study concept and design, analysis and interpretation of the data, study
supervision. B. Egan: acquisition of data. N.A. Le: acquisition of data.
M. Lopes-Virella: acquisition of data. K. Hermayer: acquisition of data.
J. Harrell: acquisition of data. C. Derdeyn: study concept and design,
study supervision. D. Fiorella: study concept and design, study supervision. L.S. Janis: study supervision. B. Lane: study concept and design,
study supervision. J. Montgomery: acquisition of data. M. Chimowitz:
study concept and design, study supervision.

ACKNOWLEDGMENT
The PACE self-assessment forms for smoking cessation and physical activity were provided by the San Diego Center for Health Interventions, LLC.

STUDY FUNDING
This study was funded by a research grant (U01 NS058728) from the US
Public Health Service National Institute of Neurologic Disorders andStroke (NINDS). In addition, the following Clinical and Translational
Science Awards, funded by the NIH, provided local support for the evaluation of patients in the trial: Medical University of South Carolina(UL1RR029882), University of Florida (UL1RR029889), University ofCincinnati (UL1RR029890), and University of California, San Francisco(UL1RR024131). Corporate Support: Stryker Neurovascular (formerly
Boston Scientific Neurovascular) provided study devices and supplemental funding for third-party device distribution, site monitoring, and study
auditing. This research was also supported by the Investigator-Sponsored
Study Program of AstraZeneca, which donated rosuvastatin (Crestor) to
study patients. Vendors: INTERVENT provided the lifestyle modification program to the study at a discounted rate. The Regulatory and Clinical Research Institute (RCRI) (Minneapolis, MN) provided assistance indesigning the site monitoring processes and performing the site monitoring visits. The VA Cooperative Studies Program Clinical Research
Pharmacy Coordinating Center (Albuquerque, NM) handled the384

Neurology 88

procurement, labeling, distribution, and inventory management of thestudy devices and rosuvastatin. Walgreens pharmacies provided study
medications except rosuvastatin to patients at a discounted price (paidfor by the study).

DISCLOSURE
T. Turan reports grants from NIH/NINDS related to this study and personal fees from Gore and Boehringer Ingelheim for participating asa stroke adjudicator in clinical trials unrelated to this work. A. Nizam reports grants from NINDS during the conduct of the study. M. Lynn reports grants from NINDS during the conduct of the study. B. Egan
received research support from Medtronic, Takeda, and Novartis, andhas been a consultant for Medtronic and Blue Cross. N.A. Le reports
grants from NINDS during the conduct of the study. M. Lopez-Virella
reports no disclosures relevant to the manuscript. K. Hermayer received
research support from the American Diabetes Association (ADA), SanofiAventis, Eli Lilly, Novo Nordisk, and the NIH (DCCT/EDIC trial).
Dr. Hermayer has received speakers’ bureau appointment payments from
Sanofi-Aventis, Eli Lilly, Amylin, and Boehringer Ingelheim. J. Harrell
reports no disclosures relevant to the manuscript. C. Derdeyn reports
grants from NINDS during the conduct of the study and has relationships with companies that manufacture medical devices for the treatmentof cerebrovascular disease in general, although none was directly involvedin this study (W.L. Gore and Associates [Scientific Advisory Board andConsultant]; Microvention, Inc. [Angiographic Core Lab for clinical
trial]; Penumbra, Inc. [DSMB member for clinical trial]; and Pulse Therapeutics [Chair, Scientific Advisory Board]). D. Fiorella reports Siemens
Microintervention institutional payment for research/salary support; Covidien Ev3, Cordis, NFocus Medical, and Micrus Endovascular consulting
fees; Codman & Shurtleff (REVIVE) royalties; and Vascular Simulators
LLC, TDC Technologies, and CVSL ownership and stock interests.
L. Janis, B. Lane, and J. Montgomery report no disclosures relevant to
the manuscript. M. Chimowitz reports grants from NIH/NINDS andother support from AstraZeneca and Stryker Neurovascular (formerly
Boston Scientific Neurovascular) related to this study; other grants from
NIH/NINDS and personal fees from Gore Associates, Merck/Parexel,and Medtronic for participating as a stroke adjudicator or data safety
monitoring board member on clinical trials unrelated to the submitted
work; and personal fees as an expert witness in medical legal cases related
to stroke. Go to Neurology.org for full disclosures.

Received April 30, 2016. Accepted in final form October 11, 2016.
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This Week’s Neurology® Podcast
Relationship between risk factor control and vascular eventsin the SAMMPRIS trial (see p. 379)
This podcast begins and closes with Dr. Robert Gross, Editor-inChief, briefly discussing highlighted articles from the January 24,
2017, issue of Neurology. In the first segment, Dr. Joseph Carrera
talks with Dr. Tanya Turan about her paper on risk factor control and vascular events in the SAMMPRIS trial. Dr. Ted Burns
then talks with Christy Phelps about the 2017 AAN Annual
Meeting for our “What’s Trending” feature of the week. In thenext part of the podcast, Dr. Ted Burns focuses his interview
with Dr. Anthony Amato on myositis.
Disclosures can be found at Neurology.org.
At Neurology.org, click on “RSS” in the Neurology Podcast box to listen to the most recent
podcast and subscribe to the RSS feed.
CME Opportunity: Listen to this week’s Neurology Podcast and earn 0.5 AMA PRA Category
1 CME Credits™ by answering the multiple-choice questions in the online Podcast quiz.

Neurology 88

January 24, 2017385

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