Clinical Review & Education
JAMA Clinical Guidelines Synopsis
Primary Prevention of Stroke
Nathaniel Steiger, MD; Adam S. Cifu, MD
GUIDELINE TITLE Guidelines for the Primary Prevention of Stroke
DEVELOPER American Heart Association (AHA)/American
Stroke Association (ASA)
RELEASE DATES October 28, 2014 (online); December 11, 2014
(print)
PRIOR VERSION February 15, 2011
FUNDING SOURCE AHA/ASA
TARGET POPULATION Adults
MAJOR RECOMMENDATIONS
Assess the risk of first stroke in adults using a risk assessment
tool such as the American College of Cardiology (ACC)/AHA
Cardiovascular Risk Calculator (class IIa; level of evidence B).
Summary of the Clinical Problem
Approximately 6.6 million Americans have had a stroke, and this
prevalence is projected to increase by 20.5% by the year 2030.2,3
Of all strokes, 87% are ischemic whereas 13% are hemorrhagic.2
Stroke is a leading cause of long-term US disability. Among Medi-
care patients hospitalized with stroke, more than half are dis-
charged to inpatient rehabilitation or a skilled nursing facility.2 Pri-
mary prevention of stroke is important because most strokes occur
in people without known cerebrovascular disease.3 Preventing stroke
depends on identifying risk factors, implementing appropriate life-
style changes, and intervening to control modifiable risk factors.
Characteristics of the Guideline Source
The guideline (Table) was developed by the AHA and the ASA.4 Writ-
ing group members were nominated by the committee chair based on
their previous work. Members of the writing group submitted a disclo-
sure questionnaire to evaluate real or potential conflicts of interest. Re-
gardless of disclosures, all members of the writing group were allowed
to participate and had the opportunity to comment on the recommen-
dations. The guideline underwent peer review by the Stroke Council
Leadership and Scientific Statements Oversight committees before
being approved by the AHA Science Advisory and Coordinating Com-
mittee for publication. The guideline has been endorsed by the Ameri-
can Association of Neurological Surgeons, the Congress of Neurologi-
cal Surgeons, and the Preventive Cardiovascular Nurses Association.
Evidence Base
Recommendations for physical activity were based on 2 meta-
analyses of observational data demonstrating that physically active
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Encourage lifestyle habits that promote physical activity
(class I; level of evidence B), a diet low in sodium and rich in
fruits and vegetables (class I; level of evidence A),
and smoking cessation using counseling and drug therapy
(class I; level of evidence A).
Treat patients estimated to have a !7.5% 10-year risk
of cardiovascular events as recommended in the 2013
ACC/AHA Guideline on the Treatment of Blood Cholesterol
to Reduce Atherosclerotic Cardiovascular Risk in Adults
(class I; level of evidence A).1
In patients with nonvalvular atrial fibrillation (AF) and
a CHA2DS2-VASc score of !2 and acceptably low risk
of complications, anticoagulation with either warfarin
(class I; level of evidence A), dabigatran, apixaban, or rivar-
oxaban (class I; level of evidence B) is recommended.
Use of aspirin for cardiovascular disease (CVD) prophylaxis is
reasonable for people who have a 10-year risk of a cardiovascu-
lar event >10% (class IIa; level of evidence A).
Aspirin is not useful in preventing stroke in people at low risk
(class III; level of evidence A).
people have a 25% to 30% lower risk of ischemic stroke, hemor-
rhagic stroke, or mortality than the least active.4 Diet recommenda-
tions focus on reduced sodium intake and emphasize fruits and veg-
etables, with 1 study showing a dose-response relationship (a 6%
reduction in risk of ischemic stroke with each serving-per-day in-
crease of fruits or vegetables).4 Recommendations for smoking ces-
sation were based on multiple studies, including a meta-analysis of
32 studies that estimated the relative risk to be 1.9 for ischemic stroke,
2.9 for subarachnoid hemorrhage, and 0.74 for intracranial hemor-
rhage in smokers vs nonsmokers.4
Treatment recommendations for patients at high risk of stroke
with statins (class 1; level of evidence A) were based on numerous
randomized clinical trials and meta-analyses published in the past
15 years. One meta-analysis that included more than 90 000 pa-
tients found that statins were associated with a reduction in the risk
of all strokes by approximately 21%.5
Table. Guideline Rating
Standard Rating
Establishing transparency Good
Management of conflict of interest in the guideline Fair
development group
Guideline development group composition Good
Clinical practice guidelinesystematic review intersection Good
Establishing evidence foundations and rating strength for Good
each of the guideline recommendations
Articulation of recommendations Good
External review Fair
Updating Fair
Implementation issues Good
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 JAMA Clinical Guidelines Synopsis Clinical Review & Education

Recommendations for anticoagulation with use of novel oral an-
ticoagulants (NOAC) in patients with nonvalvular AF were based on
randomized trials of each NOAC vs warfarin. Most recommenda-
tions regarding screening patients based on increased genetic risk
were based on consensus opinion of experts.
The guidelines recommendation for using aspirin for cardio-
vascular prophylaxis was taken from the 2002 AHA guideline on pri-
mary prevention of CVD and stroke.6 This recommendation was
based on the US Preventive Services Task Force (USPSTF) report in
2002 using data pooled from 5 randomized clinical trials that pri-
marily consisted of men older than 50 years; 2 of the trials included
women, 2 included only physicians, and race was not mentioned.6
The USPSTF analysis demonstrated a reduction in myocardial in-
farction of approximately 8 fewer coronary heart disease (CHD)
events per 1000 patients over 5 years with aspirin. These people had
a 5-year CHD risk of 3%. In this same analysis, aspirin precipitated 4
major hemorrhagic events and there was no change in all-cause mor-
tality.
Use of aspirin for stroke prevention in low-risk individuals was
not recommended based on multiple meta-analyses and observa-
tional studies. Aspirin did not result in a net reduction of stroke in
low-risk individuals in the general population and was associated with
an increased risk of gastrointestinal bleeding and hemorrhagic stroke
by 2 hemorrhagic events per 1000 person-years.4
Benefits and Harms
Consistent adherence to lifestyle modification (regular physical ac-
tivity, maintenance of healthful diet, and cessation of cigarette smok-
ing) is difficult for most people and is often not sufficient for those
at higher risk of stroke. Statins reduce the risk of ischemic stroke in
patients at high risk of atherosclerosis and are well tolerated.4 Con-
cerns about increasing the risk of hemorrhagic stroke from lower-
ing low-density lipoproteins with statin therapy have not been
supported.7 The benefits of nonstatin lipid-modifying therapies on
decreasing stroke risk are not well established.
In patients with nonvalvular AF and a CHA2DS2-VASc score of 2
or higher, concerns exist about harm from NOACs, including lack of
agents to reverse their effects and the clustering of stroke that has
been observed in the days after medication discontinuation.4
Use of aspirin for prophylaxis is reasonable in people with a 10-
year atherosclerotic CVD risk higher than 10%. In the general popu-
lation, aspirin exposes individuals to increased bleeding risk with no
benefit for prevention of first stroke. In addition, aspirin has no ben-
efit for preventing first stroke in people with diabetes mellitus in the
absence of other high-risk conditions.4
Critics of the risk calculator have raised concerns that it over-
estimates the level of vascular risk by 75% to 150%.8 The risk cal-
culator may underestimate the risk for Hispanics, Asian Americans,
and American Indians, populations who already have a dispropor-
tionately higher incidence of stroke and are projected to have the
highest increase in the next decades.2,9
Discussion
Rather than using any single risk factor, the guideline emphasized a
risk-based approach using the atherosclerotic CVD risk calculator for
instituting statin and antiplatelet therapy. Risk assessment tools can
help identify people who are at high risk of stroke who may not have
been recognized based on any single risk factor.4
The guideline continued to recommend a blood pressure treat-
ment target of less than 140/90 mm Hg in adults of all ages while
acknowledging the more liberal treatment thresholds published by
the Eighth Joint National Committee.10
Areas in Need of Future Study or Ongoing Research
Assessment tools that can more accurately predict risk, especially
in populations with higher incidence of stroke, need to be continu-
ously developed and validated.9 These tools might include more
newly recognized risk factors for stroke, such as obstructive sleep
apnea, as more data emerge. Given that hypertension remains the
most important modifiable risk factor, new data regarding blood
pressure targets in patients at increased cardiovascular risk will need
to be incorporated into future guidelines.
Related guideline
Guidelines for the Prevention of Stroke in Women: A Statement for
Healthcare Professionals From the AHA/ASA

ARTICLE INFORMATION from the American Heart Association. Circulation. 7. McKinney JS, Kostis WJ. Statin therapy and the
Author Affiliations: Department of Medicine, 2016;133(4):e38-e60. risk of intracerebral hemorrhage. Stroke. 2012;43
University of Chicago, Chicago, Illinois. 3. Ovbiagele B, Goldstein LB, Higashida RT, et al. (8):2149-2156.

Corresponding Author: Adam S. Cifu, MD,
University of Chicago, 5841 S Maryland Ave, MC
3051, Chicago, IL 60637 (adamcifu@uchicago.edu).
Conflict of Interest Disclosures: The authors have
completed and submitted the ICMJE Form for
Disclosure of Potential Conflicts of Interest and
none were reported.
REFERENCES
1. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013
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Forecasting the future of stroke in the United
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4. Meschia JF, Bushnell C, Boden-Albala B, et al.
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a statement for healthcare professionals from the
American Heart Association/American Stroke
Association. Stroke. 2014;45(12):3754-3832.
5. Amarenco P, Labreuche J, Lavalle P, Touboul
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6. Pearson TA, Blair SN, Daniels SR, et al.
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guidelines for prevention of cardiovascular disease.
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9. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al.
2013 ACC/AHA guideline on the assessment
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2014 evidence-based guideline for the
management of high blood pressure in adults:
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2. Mozaffarian D, Benjamin EJ, Go AS, et al. Heart AHA guidelines for primary prevention of
disease and stroke statistics2016 update: a report cardiovascular disease and stroke: 2002 update.
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