A report of the American College of Cardiology/American Heart Association
Task Force on Clinical Practice Guidelines
CITATION: J Am Coll Cardiol. Nov 2018; DOI: 10.1016/j.jacc.2018.11.003
Scott M. Grundy, MD, PhD, FAHA, Chair
Neil J. Stone, MD, FACC, FAHA, Vice Chair
Alison L. Bailey, MD, FACC, FAACVPR
Craig Beam, CRE
Kim K. Birtcher, MS, PharmD, AACC, FNLA
Roger S. Blumenthal, MD, FACC, FAHA, FNLA
Lynne T. Braun, PhD, CNP, FAHA, FPCNA, FNLA
Sarah de Ferranti, MD, MPH
Joseph Faiella-Tommasino, PhD, PA-C
Daniel E. Forman, MD, FAHA
Ronald Goldberg, MD
Paul A. Heidenreich, MD, MS, FACC, FAHA
Mark A. Hlatky, MD, FACC, FAHA
Daniel W. Jones, MD, FAHA
Donald Lloyd-Jones, MD, SCM, FACC, FAHA
Nuria Lopez-Pajares, MD, MPH
Chiadi E. Ndumele, MD, PhD, FAHA
Carl E. Orringer, MD, FACC, FNLA
Carmen A. Peralta, MD, MAS
Joseph J. Saseen, PharmD, FNLA, FAHA
Sidney C. Smith, Jr, MD, MACC, FAHA
Laurence Sperling, MD, FACC, FAHA, FASPC
Salim S. Virani, MD, PhD, FACC, FAHA
Joseph Yeboah, MD, MS, FACC, FAHA
Writing Committee:
The purpose of the present guideline is to address the practical management of patients with high
blood cholesterol and related disorders. The 2018 Cholesterol Guideline is a full revision of the 2013
ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular
Risk in Adults.
The following resource contains tables and gures from the 2018 Guideline for the Management of
Blood Cholesterol. The resource is only an excerpt from the Guideline and the full publication should
be reviewed for more tables and gures as well as important context.
2018 Guideline on the Management of Blood Cholesterol
GUIDELINES MADE SIMPLE
Top Ten Messages to Reduce Risk of ASCVD ……………………………………………………………… 4-6
ACC JACC Central Illustration: Overview of Primary and Secondary ASCVD Prevention …………………… 7
Four Statin Benefit Groups:
1. Secondary ASCVD Prevention
- Clinical ASCVD: Figure 1 ……………………………………………………………………… 8
- Criteria for Very High Risk ASCVD …………………………………………………………… 9
2. Severe Hypercholesterolemia (LDL-C ≥190)
- Recommendations for Primary Severe Hypercholesterolemia
[LDL-C ≥190 mg/dL (≥4.9 mmol/L)] ……………………………………………………… 10
3. Diabetes Mellitus in Adults 40-75 Years of Age With LDL- C 70-189 mg/dL
- Risk Enhancers That Are Independent of Other Risk Factors in Diabetes ……………… 11
4. Primary Prevention Over the Life Span
- Primary Prevention: Figure 2 ……………………………………………………………… 12
- Risk-enhancing Factors for Clinician-Patient Risk Discussion …………………………… 13
- Checklist for Clinician-Patient Shared Decision Making for Initiating Therapy ………… 14
- Selected Examples of Candidates for Coronary Artery Calcium Who Might Benet
from Knowing CAC=0 (In Selected patients if Risk Decision Uncertain) ……………… 15
Treatment Considerations:
•High-, Moderate-, and Low-Intensity Statin Therapy ……………………………………………… 16
•Statin Associated Side Effects (SASS) ………………………………………………………… 17-18
Special Populations:
•Normal and Abnormal Lipid Values in Childhood………………………………………………… 19
•Ethnicity Issues in Evaluation, Risk Decisions, and Treatment of ASCVD Risk ……………… 20-22
Selected Table or Figure Page
2018 Guideline on the Management of Blood Cholesterol
GUIDELINES MADE SIMPLE
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Top 10 Take-Home Messages to Reduce Risk of Atherosclerotic
Cardiovascular Disease (ASCVD) through Cholesterol Management
(1 of 3)
A healthy lifestyle reduces atherosclerotic cardiovascular disease (ASCVD) risk at all ages. In younger individuals, healthy
lifestyle can reduce development of risk factors and is the foundation of ASCVD risk reduction. In young adults 20 to
39 years of age, an assessment of lifetime risk facilitates the clinician–patient risk discussion (see #6) and emphasizes
intensive lifestyle efforts. In all age groups, lifestyle therapy is the primary intervention for metabolic syndrome.
1
In all individuals, emphasize heart-healthy lifestyle
across the life-course.
The more LDL-C is reduced on statin therapy, the greater will be subsequent risk reduction. Use a maximally tolerated
statin to lower LDL-C levels by ≥50%.
2
In patients with clinical ASCVD, reduce low-density
lipoprotein cholesterol (LDL-C) with high-intensity statin
therapy or maximally tolerated statin therapy
Very high-risk includes a history of multiple major ASCVD events or 1 major ASCVD event and multiple high-risk
conditions. In very high-risk ASCVD patients, it is reasonable to add ezetimibe to maximally tolerated statin therapy
when the LDL-C level remains ≥70 mg/dL (≥1.8 mmol/L). In patients at very high risk whose LDL-C level remains
≥70 mg/dL (≥1.8 mmol/L) on maximally tolerated statin and ezetimibe therapy, adding a PCSK9 inhibitor is rea-
sonable, although the long-term safety (>3 years) is uncertain and cost effectiveness is low at mid-2018 list prices.
3
In very high-risk ASCVD, use a LDL-C threshold of 70 mg/dL
(1.8 mmol/L) to consider addition of nonstatins to statin therapy.
If the LDL-C level remains ≥100 mg/dL (≥2.6 mmol/L), adding ezetimibe is reasonable. If the LDL-C level on statin
plus ezetimibe remains ≥100 mg/dL (≥2.6 mmol/L) and the patient has multiple factors that increase subsequent
risk of ASCVD events, a PCSK9 inhibitor may be considered, although the long-term safety (>3 years) is uncertain
and economic value is uncertain at mid-2018 list prices.
4
In patients with severe primary hypercholesterolemia (LDL-C
level ≥190 mg/dL [≥4.9 mmol/L]), without calculating 10-year
ASCVD risk, begin high-intensity statin therapy.
“Top Ten Messages” is continued in the next page.
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In patients with diabetes mellitus at higher risk, especially those with multiple risk factors or those 50 to 75
years of age, it is reasonable to use a high-intensity statin to reduce the LDL-C level by ≥50%.
5
In patients 40 to 75 years of age with diabetes mellitus and
LDL-C ≥70 mg/dL (≥1.8 mmol/L), start moderate-intensity
statin therapy without calculating 10-year ASCVD risk.
Risk discussion should include a review of major risk factors (e.g., cigarette smoking, elevated blood pressure,
LDL-C, hemoglobin A1C [if indicated], and calculated 10-year risk of ASCVD); the presence of risk-enhancing factors
(see #8); the potential benets of lifestyle and statin therapies; the potential for adverse effects and drug–drug
interactions; consideration of costs of statin therapy; and patient preferences and values in shared decision-making.
6
In adults 40 to 75 years of age evaluated for primary
ASCVD prevention, have a clinician–patient risk discussion
before starting statin therapy.
. Risk-enhancing factors favor statin therapy (see #8). If risk status is uncertain, consider using coronary artery
calcium (CAC) to improve specicity (see #9). If statins are indicated, reduce LDL-C levels by ≥30%, and if 10-
year risk is ≥20%, reduce LDL-C levels by ≥50%.
7
In adults 40 to 75 years of age without diabetes mellitus and
with LDL-C levels ≥70 mg/dL (≥1.8 mmol/L), at a 10-year
ASCVD risk of ≥7.5%, start a moderate-intensity statin if a
discussion of treatment options favors statin therapy.
“Top Ten Messages” is continued in the next page.
Top 10 Take-Home Messages to Reduce Risk of Atherosclerotic
Cardiovascular Disease (ASCVD) through Cholesterol Management
(2 of 3)
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If CAC is zero, treatment with statin therapy may be withheld or delayed, except in cigarette smokers, those with
diabetes mellitus, and those with a strong family history of premature ASCVD. A CAC score of 1 to 99 favors statin
therapy, especially in those ≥55 years of age. For any patient, if the CAC score is ≥100 Agatston units or ≥75th per-
centile, statin therapy is indicated unless otherwise deferred by the outcome of clinician–patient risk discussion.
9
In adults 40 to 75 years of age without diabetes mellitus and
with LDL-C levels ≥70 mg/dL- 189 mg/dL (≥1.8-4.9 mmol/L),
at a 10-year ASCVD risk of ≥7.5% to 19.9%, if a decision about
statin therapy is uncertain, consider measuring CAC.
Dene responses to lifestyle and statin therapy by percentage reductions in LDL-C levels compared with base-
line. In ASCVD patients at very high-risk, triggers for adding nonstatin drug therapy are dened by threshold
LDL-C levels ≥70 mg/dL (≥1.8 mmol/L) on maximal statin therapy (see #3).
10
Assess adherence and percentage response to LDL-C–lowering
medications and lifestyle changes with repeat lipid measurement
4 to 12 weeks after statin initiation or dose adjustment, repeat-
ed every 3 to 12 months as needed.
Risk-enhancing factors include family history of premature ASCVD; persistently elevated LDL-C levels ≥160 mg/dL
(≥4.1 mmol/L); metabolic syndrome; chronic kidney disease; history of preeclampsia or premature menopause
(age <40 years); chronic inammatory disorders (e.g., rheumatoid arthritis, psoriasis, or chronic HIV); high-risk
ethnic groups (e.g., South Asian); persistent elevations of triglycerides ≥175 mg/dL (≥1.97 mmol/L); and, if
measured in selected individuals, apolipoprotein B ≥130 mg/dL, high-sensitivity C-reactive protein ≥2.0 mg/L,
ankle-brachial index <0.9 and lipoprotein (a) ≥50 mg/dL or 125 nmol/L, especially at higher values of lipopro-
tein (a). Risk-enhancing factors may favor statin therapy in patients at 10-year risk of 5-7.5% (borderline risk).
8
In adults 40 to 75 years of age without diabetes mellitus and
10-year risk of 7.5% to 19.9% (intermediate risk), risk-enhanc-
ing factors favor initiation of statin therapy (see #7).
Top 10 Take-Home Messages to Reduce Risk of Atherosclerotic
Cardiovascular Disease (ASCVD) through Cholesterol Management
(3 of 3)
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This tool provides a broad overview of the 2018 Cholesterol Guideline.
Please refer to the full guideline document for specic recommendations.
Overview of Primary and Secondary ASCVD Prevention
The ACC Cholesterol Guideline Clinical
Tool Work Group decided to remove the
Overview of Primary and Secondary
ASCVD Prevention tool in order to
minimize confusion about the full range
of information covered in the guideline.
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High-intensity or maximal statin
(Class I)
If on maximal
statin &
LDL-C ≥70
mg/dL
(≥1.8 mmol/L),
adding
ezetimibe is
reasonable
(Class IIa)
If PCSK9-I
is considered,
add ezetimibe
to maximal
statin before
adding
PCSK9-I
(Class I)
Dashed arrow
indicates
RCT-supported
efcacy,
but is less
cost effective
If on clinically judged-maximal LDL-C lowering
therapy & LDL-C ≥70 mg/dL (≥1.8 mmol/L),
or non-HDL-C ≥100 mg/dL (≥2.6 mmol/L),
adding PCSK9-I is reasonable
(Class IIa)
Age ≤75 yrs
High-intensity statin
(Goal: LDL-C ≥50%)
(Class I)
If high-
intensity
statin not
tolerated,
use
moderate-
intensity
statin
(Class I)
If on
maximal statin
& LDL-C ≥70
mg/dL
(≥1.8 mmol/L),
adding
ezetimibe
may be
reasonable
(Class IIb)
Age >75
ASCVD not at very high-risk* Very high-risk* ASCVD
Healthy Lifestyle
Initiation of
moderate or
high-intensity
statin is
reasonable
(Class IIa)
Continuation
of
high-intensity
statin is
reasonable
(Class IIa)
Clinical
ASCVD
Figure 1:
Secondary Prevention in Patients with Clinical ASCVD
Figure 1
Secondary ASCVD Prevention
First Statin Benet Group
*Very high-risk includes a history of multiple major ASCVD events or 1 major ASCVD event and multiple high-risk conditions (Table 4 on
following page).
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Recent acute coronary syndrome (within the past 12 months)
History of myocardial infarction (other than recent acute coronary syndrome event listed above)
History of ischemic stroke
Symptomatic peripheral arterial disease (history of claudication with ankle brachial index <0.85,
or previous revascularization or amputation)
Age ≥65 years
Heterozygous familial hypercholesterolemia
History of prior coronary artery bypass surgery or PCI outside of the major ASCVD event(s)
Diabetes Mellitus
Hypertension
Chronic kidney disease (eGFR 15-59 mL/min/1.73 m
2
)
Current smoking
Persistently elevated LDL-C (LDL-C ≥100 mg/dL (≥2.6 mmol/L)) despite maximally tolerated
statin therapy and ezetimibe
History of congestive heart failure
Major ASCVD Events
High-Risk Conditions
Table 4
Very High-Risk for Future ASCVD Events*
Secondary ASCVD Prevention
First Statin Benet Group
*Very High Risk includes a history of multiple major ASCVD events or one major ASCVD event and multiple high-risk conditions.
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COR LOE Recommendations
1. In patients 20 to 75 years of age with an LDL-C level of 190 mg/dL
or higher, (≥4.9 mmol/L) maximally tolerated statin therapy is
recommended.
2. In patients 20 to 75 years of age with an LDL-C level of 190 mg/dL
or higher (≥4.9 mmol/L) who achieve less than 50% reduction in
LDL-C while receiving maximally tolerated statin therapy and/or have
an LDL-C level of 100 mg/dL (≥2.6 mmol/L) or higher, ezetimibe
therapy is reasonable.
3. In patients 20 to 75 years of age with a baseline LDL-C 190 mg/dL
or higher (≥4.9 mmol/L), who achieve less than a 50% reduction
in LDL-C levels and have fasting triglycerides 300 mg/dL or lower
(≤3.4 mmol/L) while taking maximally tolerated statin and ezetimibe
therapy, the addition of a bile acid sequestrant may be considered.
4. In patients 30 to 75 years of age with heterozygous FH and with an
LDL-C level of 100 mg/dL or higher (≥2.6 mmol/L) while taking
maximally tolerated statin and ezetimibe therapy, the addition of a
PCSK9 inhibitor may be considered.
5. In patients 40 to 75 years of age with a baseline LDL-C level of 220
mg/dL or higher (≥5.7 mmol/L) who achieve an on-treatment LDL-C
level of 130 mg/dL or higher (≥3.4 mmol/L) while receiving
maximally tolerated statin and ezetimibe therapy, the addition of a
PCSK9 inhibitor may be considered.
6. Among patients with FH without evidence of clinical ASCVD taking
maximally tolerated statin and ezetimibe therapy, PCSK9 inhibitors
provide uncertain value at mid-2018 US list prices.
B-R
B-R
B-R
B-R
C-LD
I
IIa
IIb
IIb
IIb
Value Statement:
Uncertain Value
(B-NR)
Recommendations for Primary Severe Hypercholesterolemia
[LDL-C ≥190 mg/dL (≥4.9 mmol/L)]
Severe Hypercholesterolemia
Second Statin Benet Group
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• Long duration (≥10 years for type 2 diabetes or ≥ 20 years for type 1 diabetes)
• Albuminuria ≥30 mcg albumin/mg creatinine
• eGFR <60 ml/min/1.73 m
2
• Retinopathy
• Neuropathy
• ABI <0.9
Diabetes-specic Risk Enhancers
That Are Independent of Other Risk Factors in Diabetes
Table 5
Diabetes Mellitus in Adults
Third Statin Benet Group
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LDL-C ≥190 mg/dL (≥4.9 mmol/L)
No risk assessment; High-
intensity statin
(Class I)
Diabetes mellitus and age 40-75 y
Moderate-intensity statin
(Class I)
Diabetes mellitus and age 40-75 y
Risk assessment to consider
high-intensity statin
(Class IIa)
Age >75 y
Clinical assessment, Risk discussion
ASCVD Risk Enhancers:
•Family history of premature
ASCVD
•Persistently elevated
LDL-C ≥160 mg/dL
(≥4.1 mmol/L)
•Chronic kidney disease
•Metabolic syndrome
•Conditions specic to women
(e.g. preeclampsia, premature
menopause)
•Inammatory diseases
(especially rheumatoid
arthritis, psoriasis, HIV)
•Ethnicity factors
(e.g. South Asian ancestory)
Lipid/Biomarkers:
•Persistently elevated
triglycerides (≥175 mg/mL)
In selected individuals
if measured:
•hs-CRP ≥2.0 mg/L
•Lp(a) levels >50 mg/dL or
>125 nmol/L
•apoB ≥130 mg/dL
•Ankle-brachial index (ABI) <0.9
Age 20-39 y
Estimate lifetime risk
to encourage lifestyle
to reduce ASCVD risk
Consider statin if family
history, premature ASCVD
and LDL-C ≥160 mg/dL
(≥4.1 mmol/L)
Age 40-75 y and
LDL-C ≥70 to <190
mg/dL
(≥1.8 - <4.9 mmol/L)
without
diabetes mellitus
10-year ASCVD risk
percent begins
risk discussion
Risk
Discussion:
initiate statin
to reduce
LDL-C ≥50%
Class (I)
Risk Discussion:
If risk estimate + risk enhancers
favor statin, initiate moderate-
intensity statin to reduce
LDL-C by 30% - 49%
Class (I)
Risk
Discussion:
Emphasize
lifestyle to
reduce risk
factors
Class (I)
<5%
“Low Risk”
5% - <7.5%
“Borderline Risk”
≥7.5% - <20%
“Intermediate Risk”
≥20%
“High Risk”
If risk decision is uncertain:
Consider measuring CAC in selected adults:
CAC = zero (lowers risk; consider no statin, unless diabetes,
family history of premature CHD, or cigarette smoking are present)
CAC = 1-99 favors statin (especially after age 55)
CAC = 100+ and/or ≥75
th
percentile, initiate statin therapy
If Risk
enhancers
present then
risk discussion
regarding
moderate-
intensity statin
therapy
Class (IIb)
Primary Prevention:
Assess ASCVD Risk in Each Age Group
Emphasize Adherence to Healthy Lifestyle
Age 0-19 y
Lifestyle to prevent or
reduce ASCVD risk
Diagnosis of Familial
Hypercholesterolemia
statin
Primary Prevention
Figure 2
Primary Prevention Over The Life Span
Fourth Statin Benet Group
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• Family history of premature ASCVD; (males <55 years; females <65 years)
• Primary hypercholesterolemia (LDL-C 160-189 mg/dL (4.1- 4.8 mmol/L); non-HDL-C 190-219 mg/dL
(4.9-5.6 mmol/L).
• Metabolic syndrome (increased waist circumference, elevated TG (>150 mg/dL, elevated BP, elevated glucose,
low HDL-C (<40 mg/dL in men, <50 mg/dL in women) are factors; tally of 3 makes the diagnosis)
• Chronic kidney disease (eGFR 15- 59 ml/min per 1.73 m
2
with or without albuminuria; not treated with dialysis
or kidney transplantation)
• Chronic inammatory conditions such as psoriasis, rheumatoid arthritis (RA) or human immunodeciency
virus (HIV)/acquired immunodeciency syndrome (AIDS)
• History of premature menopause (before age 40) and history of pregnancy-associated
conditions that increase later ASCVD risk such as pre-eclampsia
• High-risk ethnicities (e.g. South Asian ancestry)
• Lipid/Biomarkers: Associated with increased ASCVD risk
-Persistently* elevated, primary hypertriglyceridemia ( ≥175 mg/dl);
-If measured:
• High-sensitivity C-reactive protein - (≥2.0 mg/L)
• Elevated lipoprotein (a) - A relative indication for its measurement is family history of premature ASCVD.
An Lp(a) ≥ 50 mg/dL or ≥125 nmol/L constitutes a risk enhancing factor especially at higher levels of Lp(a).
• Elevated apo B ≥130 mg/dL - A relative indication for its measurement would be triglyceride ≥ 200 mg/dL.
A level ≥ 130 mg/dL corresponds to an LDL-C ≥160 mg/dL and constitutes a risk enhancing factor.
• ABI <0.9
Risk-enhancing Factors for Clinician-Patient
Risk Discussion
AIDS indicates acquired immunodeciency syndrome; ABI, ankle-brachial index; apoB, apolipoprotein B; ASCVD, atherosclerotic
cardiovascular disease; eGFR, estimated glomerular ltration rate; HDL-C, high-density lipoprotein cholesterol; HIV, human
immunodeciency virus; LDL-C, low-density lipoprotein cholesterol; Lp(a), lipoprotein (a); and RA, rheumatoid arthritis.
*Optimally, 3 determinations
Treatment Considerations
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•Assign to statin treatment group; use ASCVD risk estimator plus*
• In lower risk primary prevention adults 40-75 years with LDL-C ≥70 mg/dL (≥1.8 mmol/L).
• Not needed in secondary prevention, LDL-C ≥190 mg/dL (≥4.9 mmol/L) and those 40-75
years with diabetes.
•Assess other patient characteristics which inuence risk. See Risk Enhancing Factors
(Section 4.4.1.3 and Table 6)
•Assess coronary artery calcium (section 4.4.1.4) if risk decision uncertain and additional
information is needed to clarify ASCVD risk
• Use decision tools to explain risk (ASCVD risk estimator plus-
http://tools.acc.org/ASCVD-Risk-Estimator-Plus, Mayo Clinic Statin Choice Decision Aid)
Checklist Item Recommendation
ASCVD Risk
Assessment
•Review lifestyle habits (diet, physical activity, weight/BMI, tobacco use)
•Endorse a healthy lifestyle and provide relevant advice/materials/referrals (CardioSmart,
AHA Life's Simple 7, NLA Patient Tear Sheets, PCNA Heart Healthy Toolbox, cardiac rehab,
dietitian, smoking cessation program)
•Recommend statins as rst-line therapy
•Consider the combination of statin and non-statin therapy in select patients
•Discuss potential risk reduction from lipid-lowering therapy
•Discuss the potential for adverse effects/drug-drug interactions
Lifestyle
Modications
Potential
Net-Clinical
Benet of
Pharmacotherapy
•Discuss potential out-of-pocket cost of therapy to the patient (e.g., insurance plan
coverage, tier level, copayment)
Cost
Considerations
•Encourage patient to verbalize what was heard (personal ASCVD risk, available options
and their risk/benet)
•Invite the patient to ask questions, express values/preferences, state ability to adhere to
lifestyle changes and medications
•Refer patients to trustworthy materials to aid in their understanding of issues regarding
risk decisions
•Collaborate with the patient to determine therapy and follow-up plan
Shared Decision
Making
Checklist for Clinician-Patient Shared Decision Making
for Initiating Therapy
Table 7
Primary Prevention Over The Life Span
Fourth Statin Benet Group
*ASCVD Risk Predictor Plus is available at: http://tools.acc.org/ASCVD-Risk-Estimator-Plus/#!/calculate/estimate/
AHA indicates American Heart Association; ASCVD, atherosclerotic cardiovascular disease; CAC, coronary
artery calcium; CKD, chronic kidney disease; HIV, human immunodeciency virus; LDL-C, low-density
lipoprotein cholesterol; and NLA, National Lipid Association.
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1. Patients reluctant to initiate statin who wish to understand their risk and potential for
benet more precisely
2. Patients concerned about need to re-institute statin therapy after discontinuation for
statin associated symptoms
3. Older patients (men 55 to 80; women 60-80 years old) with low burden of risk factors
who question whether they would benet from statin therapy
4. Middle-aged adults (40-55 years old) with PCE calculated 10-year risk for ASCVD 5 to
<7.5% with factors that increase their ASCVD risk, even though they are in a borderline
risk group
Selected Examples of Candidates
for Coronary Artery Calcium Measurement
Who Might Benet from Knowing CAC Score is Zero
Table 8
Primary Prevention Over the Life span
Fourth Statin Benet Groups
ASCVD indicates atherosclerotic cardiovascular disease; CAC, coronary artery calcium; LDL-C, low-density lipoprotein
cholesterol; and PCE, pooled cohort equations.
Caveats: If patient is intermediate risk and if a risk decision is uncertain and a CAC score is performed, it is reasonable
to withhold statin therapy unless higher risk conditions such as cigarette smoking, family history of premature ASCVD, or
diabetes are present, and to reassess CAC score in 5-10 years. Moreover, if CAC is recommended, it should be performed
in facilities that have current technology that delivers the lowest radiation possible.
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High-Intensity Moderate-Intensity Low-Intensity
LDL- C Lowering
†
≥50% 30% to 49% <30%
Statins Atorvastatin (40 mg
‡
) 80 mg Atorvastatin 10 mg (20 mg) Simvastatin 10 mg
Rosuvastatin 20 (40 mg) Rosuvastatin (5 mg) 10 mg
Simvastatin 20–40 mg
§
– Pravastatin 40 mg (80 mg) Pravastatin 10–20 mg
Lovastatin 40 mg (80 mg) Lovastatin 20 mg
Fluvastatin XL 80 mg Fluvastatin 20–40 mg
Fluvastatin 40 mg BID
Pitavastatin 1–4 mg
High-, Moderate-, and Low-Intensity Statin Therapy*
Table 3
BID indicates twice daily; FDA, U.S. Food and Drug Administration; LDL-C, low-density lipoprotein cholesterol; RCT, randomized controlled
trial; VOYAGER, an indiVidual patient data meta-analysis Of statin therapY in At risk Groups: Effects of Rosuvastatin, atorvastatin and
simvastatin; and XL, extended release.
Percent LDL-C reductions with the primary statin medications used in clinical practice (atorvastatin, rosuvastatin, simvastatin) were
estimated using the median reduction in LDL-C from the VOYAGER database (13). Reductions in LDL-C for other statin medications
(uvastatin, lovastatin, pitavastatin, pravastatin) were identied according to FDA-approved product labeling in adults with hyperlipidemia,
primary hypercholesterolemia, and mixed dyslipidemia.
Boldface type indicates specic statins and doses that were evaluated in RCTs, and the Cholesterol Treatment Trialists’2010 meta-analysis.
All these RCTs demonstrated a reduction in major cardiovascular events.
Italic type indicates statins and doses that have been approved by the FDA but were not tested in the RCTs reviewed.
*Percent reductions are estimates from data across large populations. Individual responses to statin therapy varied in the RCTs and should
be expected to vary in clinical practice.
†
LDL-C lowering that should occur with the dosage listed below each intensity.
‡
Evidence from 1 RCT only: downtitration if unable to tolerate atorvastatin 80 mg in the IDEAL (Incremental Decrease through Aggressive
Lipid Lowering) study.
§
Although simvastatin 80 mg was evaluated in RCTs, initiation of simvastatin 80 mg or titration to 80 mg is not recommended by the FDA
because of the increased risk of myopathy, including rhabdomyolysis.
Treatment Considerations
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Infrequent (1%–5%) in
RCTs/frequent (5%–10%)
in observational studies
and clinical setting
Rare
Rare
Rare
Depends on population;
more frequent if diabetes
mellitus risk factors such
as BMI ≥30, fasting blood
glucose ≥100 mg/dL;
metabolic syndrome or
A1c ≥6% are present
Age, female, low BMI,
high- risk medications
(CYP3A4 inhibitors,
OATP1B1 inhibitors),
comorbidities (HIV, renal,
liver, thyroid, pre-existing
myopathy), Asian descent,
excess alcohol, high levels
of physical activity and
trauma.
Diabetes risk factors/
metabolic syndrome
High-intensity statin
therapy
RCTs
cohorts/observational
RCTs
cohorts/observational
RCTs
Cohorts/observational
Case reports
RCTs/Meta-analyses
Statin Associated Muscle
Symptoms (SAMS)
• Myalgias (CK normal)
• Myositis/Myopathy
(CK >ULN) with concerning
symptoms/objective
weakness
• Rhabdomyolysis
(CK >10xULN + renal injury)
• Statin-associated
autoimmune myopathy (SAAM)
(HMGCR Ab’s, incomplete
resolution)
New onset Diabetes
Mellitus
Statin Associated
Frequency
Predisposing
Quality of Evidence
Side Effects Factors
Statin Associated Side Effects (SASE)
(1 of 2)
Table 11
Table 11 is continued in the next page. For references please see page 18.
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Infrequent
Rare
Rare
No denite association
Unfounded
Unfounded
Unfounded
Unfounded
Unfounded
Unfounded
RCTs/cohorts/observational
Case reports
Case reports; no increase in
memory/cognition problems
in three large scale RCTs
RCTs/meta-analyses
Liver
• Transaminase elevation 3xULN
• Hepatic Failure
CNS
• Memory/Cognition
Cancer
Other
• Renal Function
• Cataracts
• Tendon Rupture
• Hemorrhagic Stroke
• Interstitial Lung Disease
• Low Testosterone
Statin Associated
Frequency
Predisposing
Quality of Evidence
Side Effects Factors
Statin Associated Side Effects (SASE)
(2 of 2)
Table 11 (continued from previous page)
CK indicates creatine kinase; HIV, human immunodeciency virus; HMGCR, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase; SAMS,
statin-associated muscle symptoms; SAAM, statin-associated autoimmune myopathy; SASE, statin associated side effects; and ULN, upper
limit of normal. “
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Acceptable Borderline Abnormal
TC <170 mg/dL (<4.3 mmol/L) 170-199 mg/dL (4.3-5.1 mmol/L) ≥200 mg/dL (≥5.1 mmol/L)
Triglycerides:
0-9 y <75 mg/dL (<0.8 mmol/L) 75-99 mg/dL (0.8-1.1 mmol/L) ≥100 mg/dL (≥1.1 mmol/L)
Triglycerides:
10-19 y < 90 mg/dL (<1.0 mmol/L) 90-129 mg/dL (1.0-1.5 mmol/L) ≥130 mg/dL (≥1.4 mmol/L)
HDL-C >45 mg/dL (>1.2 mmol/L) 40-45 mg/dL (1.0-1.2 mmol/L) <40 mg/dL (<1.0 mmol/L)
LDL-C <110 mg/dL (<2.8 mmol/L) 110-129 mg/dL (2.8-3.3 mmol/L) ≥130 mg/dL (≥3.4 mmol/L)
Non-HDL-C <120 mg/dL (<3.1 mmol/L) 120-144 mg/dL (3.1-3.7 mmol/L) ≥145 mg/dL (≥3.7 mmol/L)
Normal and Abnormal Lipid Values in Childhood
*
†
Table 9
HDL-C indicates high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; NCEP, National Cholesterol Education
Program; SI, Système international d’unités (International System of Units); and TC, total cholesterol.
Values given are in mg/dL. To convert to SI units, divide the results for TC, LDL-C, HDL-C, and non-HDL-C by 38.6; for triglycerides,
divide by 88.6.
*Values for plasma lipid and lipoprotein levels are from the NCEP Expert Panel on Cholesterol Levels in Children. Non-HDL-C
values from the Bogalusa Heart Study are equivalent to the NCEP Pediatric Panel cutpoints for LDL-C.
†
The cutpoints for high and borderline high represent approximately the 95th and 75th percentiles, respectively. Low cutpoints for
HDL-C represent approximately the 10th percentile.
Special Populations
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Ethnic/racial Asian- Hispanic/Latino-
Blacks
Comments
groupings Americans* Americans
†
African-Americans
ASCVD Issues
informed by
ethnicity
Lipid issues
informed by
ethnicity
Metabolic
issues
informed by
ethnicity
South Asian and East
Asian ASCVD risk varies
by country of origin;
Individuals from South
Asia (see below) have
increased ASCVD risk
Lower levels of HDL-C
compared to whites
Higher prevalence of
LDL-C among Asian
Indians, Filipinos,
Japanese, and
Vietnamese compared
to whites. An increased
prevalence of high TGs
was seen in all Asian
American subgroups
Increased Metabolic
Syndrome (MetS) seen
with lower waist
circumference than in
whites.
DM develops at a lower
lean body mass and at
earlier age (19-21)
Majority of risk in South
Asians explained by
known risk factors,
especially those related
to insulin resistance
Race and country of
origin together with
socioeconomic status
and acculturation level
may explain risk factor
burden more precisely.
e.g. ASCVD risk is higher
among individuals from
Puerto Rico than from
Mexico.
Hispanic/Latino women
have higher prevalence
of low HDL-C compared
to Hispanic/Latino men
DM disproportionately
present compared to
whites and blacks.
Increased prevalence
MetS, DM in Mexican
Americans compared to
whites & Puerto Ricans.
ASCVD risk
assessment in
black women
shows increased
ASCVD risk
compared to their
otherwise similar
white counter-
parts
Higher levels of
HDL-C and lower
levels of
triglycerides (TG)
than in Non-
Hispanic Whites
or Mexican-
Americans.
Increased DM
and hypertension
Heterogeneity in risk
according to racial/ethnic
groups and within
racial/ethnic groups.
Native American/Alaskan
populations have high rates
of risk factors for ASCVD
compared to non-hispanic
whites.
All ethnic groups appear
to be at greater risk for
dyslipidemia, but important
to identify those with more
sedentary behavior and
less favorable diet.
Increased prevalence of
DM. Features of MetS
vary by ethnicity. Waist
circumference, not weight,
should be used to
determine abdominal
adiposity when possible
Evaluation
Ethnicity Issues in Evaluation, Risk Decisions,
and Treatment of ASCVD Risk (1 of 3)
Table 10
Table 10 is continued in the
next page. For footnotes
please refer to pages 21
and 22.
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Ethnic/racial Asian- Hispanic/Latino-
Blacks/
Comments
groupings Americans* Americans
†
African-Americans
Pooled Cohort
Equations
(PCE)
Coronary
Artery
Calcium
(CAC) Score
No separate PCE
available; use PCE for
whites. PCE may
underestimate ASCVD
risk in South Asians
PCE may overestimate
risk in East Asians
In terms of CAC burden,
South Asian men were
similar to non-Hispanic
white men, but higher
CAC when compared
to blacks, Latinos and
Chinese Americans.
South Asian women
had similar CAC to
whites and other ethnic
women, although CAC
burden higher in older
age
No separate PCE
available; use PCE for
non-Hispanic whites.
If African American
ancestry also, then
use PCE for blacks
CAC predicts similarly in
whites and those who
identify as Hispanic/
Latino
Use PCE for
blacks
In MESA, CAC
score was highest
in whites and
Hispanic men,
with blacks having
signicantly lower
prevalence and
severity of CAC.
Country specic race/
ethnicity, along with
socio-economic status,
may affect estimation of
risk of PCE
Risk factor differences in
MESA between ethnicities
didn’t fully explain
variability in CAC However,
CAC predicted ASCVD
events over and above
traditional risk factors in
all ethnicities
Risk Decisions
Need to disaggregate Asian
and Hispanic/Latino groups
due to regional differences
in lifestyle preferences.
Challenge is to avoid
increased sodium, sugar
and calories as groups
acculturate
Lifestyle
counseling
(Utilize
principles of
Mediterranean
& DASH diets)
Utilize lifestyle
counseling to recom-
mend a heart healthy
diet consistent with
racial/ethnic preferences
to avoid weight gain,
and address BP and
lipids
Utilize lifestyle
counseling to recom-
mend a heart healthy
diet consistent with
racial/ethnic preferences
to avoid weight gain,
address BP and lipids
Utilize lifestyle
counseling to
recommend a
heart healthy
diet consistent
with racial/ethnic
preferences to
avoid weight
gain, address
BP and lipids
Treatment
(will continue in the next page)
Ethnicity Issues in Evaluation, Risk Decisions,
and Treatment of ASCVD Risk (2 of 3)
Table 10 (continued from previous page)
Table 10 is continued in the next page.
Special Populations
CK, creatine kinase; DASH, Dietary Approaches to Stop Hypertension; DM, type 2 diabetes mellitus; MESA, Multi-Ethnic Study
of Atherosclerosis; MetS, metabolic syndrome; and PCE, pooled cohort equations.
Footnotes are continued in the next page.
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Using a lower statin
intensity in Japanese
patients may give results
similar to those seen with
higher intensities in
non-Japanese patients
Clinicians should take
Asian ethnicity into
account when prescribing
dose of rosuvastatin
(see package insert).
In adults of East Asian
descent, other statins
should be used
preferentially over
simvastatin.
Intensity of
Statin therapy
and Response
to LDL-C
lowering
Safety
Japanese patients may
be sensitive to statin
dosing. In an open-
label, randomized
primary prevention trial,
Japanese participants
had a reduction in CVD
events with low-intensity
doses of pravastatin
as compared to
placebo. In a secondary
prevention trial,
Japanese participants
with CAD benetted
from a moderate-
intensity doses of
pitavastatin.
Higher rosuvastatin
plasma levels in
Japanese, Chinese,
Malay, and Asian-
Indians compared
to whites. FDA
recommends a lower
starting dose (5 mg of
rosuvastatin in Asians
vs. 10 mg in whites).
Caution urged as dose
uptitrated.
No sensitivity to statin
dosage compared to
non-Hispanic white or
black individuals
No specic safety issues
with statins related to
Hispanic/Latino ethnicity
No sensitivity
to statin dosage
compared to
non-Hispanic
white individuals
Baseline serum
CK values are
higher in blacks
than in whites.
The 95
th
percentile
race/ethnicity
specic and
sex-specic
serum CK
normal levels
are available
for assessing
changes in
serum CK.
Ethnic/racial Asian- Hispanic/Latino-
Blacks/
Comments
groupings Americans* Americans
†
African-Americans
Treatment (continued)
Ethnicity Issues in Evaluation, Risk Decisions,
and Treatment of ASCVD Risk (3 of 3)
Table 10 (continued from previous page)
*The term Asian characterizes a diverse portion of the world’s population. Individuals from Bangladesh, India, Nepal, Pakistan, and
Sri Lanka make up most of the South Asian group. Individuals from Japan, Korea, and China make up most of the East Asian group.
†
The term Hispanics/Latinos in the United States characterizes a diverse population group. This includes
white, black, and Native American races. Their ancestry goes from Europe to America, including among
these, individuals from the Caribbean, Mexico, Central and South America
Special Populations
