TR E N D S I N C A R D I O V A S C U L A R M E D I C I N E 25 (2015) 340–347

Available online at www.sciencedirect.com

www.elsevier.com/locate/tcm

2013 ACC/AHA cholesterol treatment guideline:

Paradigm shifts in managing atherosclerotic
cardiovascular disease risk
Jonathan B. Finkel, MDa, and Danielle Duffy, MDb,n
a
Thomas Jefferson University Hospital, Philadelphia, PA
b
Division of Cardiology, Department of Medicine, Sidney Kimmel Medical College at Thomas Jefferson University,
Mezzanine, Philadelphia, PA

abstract

The 2013 American College of Cardiology/American Heart Association Guideline on the Treatment of Blood Cholesterol to Reduce
Atherosclerotic Cardiovascular Risk in Adults represents a major shift from prior cholesterol management guidelines. The new
guidelines include data from individual randomized trials as well as the most comprehensive meta-analyses, and introduce several
major paradigm shifts, which include: aiming for ASCVD risk reduction as opposed to targeting LDL-C levels, advocating for the use of
evidence-based doses of statins as first line therapy, and utilizing a new risk calculator and risk cut point to guide initiation of statin
therapy. These major changes have created controversy and confusion among the medical community, with some clinicians hesitant to
embrace the shift. We review the evidence that forms the basis for these major changes, compare them to other major lipid guidelines,
and recommend an integrated approach to managing dyslipidemia to decrease atherosclerotic cardiovascular disease risk.
& 2015 Elsevier Inc. All rights reserved.

Introduction RCTs to inform specific clinical questions about reducing

Since the release of the 2013 American College of Cardiol-
ogy/American Heart Association (ACC/AHA) Guideline on
the Treatment of Blood Cholesterol to Reduce Atheroscler-
otic Cardiovascular Risk in Adults [1], there has been
considerable controversy and debate among the scientific
community. This new guideline is a significant paradigm
shift from prior lipid guidelines, specifically from the Adult
Treatment Panel (ATP) III [2]. The mission for the Expert
Panel responsible for creating the guideline was to use only
the highest quality evidence from randomized controlled
trials (RCTs) and systematic reviews or meta-analyses of
atherosclerotic cardiovascular disease (ASCVD) risk in
adults. New strategies are recommended, although the
basis for the guideline, namely the central and causal role
of atherogenic lipoproteins in the pathophysiology of
ASCVD and the critical need for treatment of such to reduce
ASCVD risk, remains. The 2013 ACC/AHA cholesterol guide-
lines focuses on identifying groups of patients that are most
likely to benefit from cholesterol treatment with HMG-CoA
reductase inhibitors (statins), the therapy that has been
consistently proven in RCTs to lower ASCVD risk. There has
been no dispute that identifying the highest risk patients
and implementing highly effective therapy are indicated,

Disclosures: Dr. Duffy has received research grants from Aegerion Pharmaceuticals; Amgen, USA; Forest Laboratories, USA; Regeneron
Pharmaceuticals; and Genentech, USA; has received honoraria from AstraZeneca and Genzyme; and serves on the Board of Directors for the
Northeast Lipid Association and the Southeastern Pennsylvania Chapter of the American Heart Association. Dr. Finkel has no disclosures.
The authors have indicated there are no conflicts of interest.
n
Corresponding author. Division of Cardiology, Department of Medicine, Sidney Kimmel Medical College at Thomas Jefferson University,
925 Chestnut Street, Mezzanine, Philadelphia, PA. Tel.: þ215 955 3607; fax: þ215 503 3976.
E-mail address: Danielle.duffy@jefferson.edu (D. Duffy).

http://dx.doi.org/10.1016/j.tcm.2014.10.015
1050-1738/& 2015 Elsevier Inc. All rights reserved.
 T R E N D S I N C A R D I O V A S C U L A R
and has great potential to reduce ASCVD and improve
outcomes. However, there has been controversy and debate
around several of the recommendations put forth by the
guidelines [3–5].
The major paradigm shifts that the 2013 ACC/AHA guidelines
have introduced are as follows: aiming for ASCVD risk reduc-
tion as opposed to targeting LDL-C levels, advocating for the
use of evidence-based doses of statins as first line therapy, and
utilizing a new risk calculator and risk cut point to guide
initiation of statin therapy. Overall, these changes result in a
simplified approach to the assessment and treatment of
cholesterol for ASCVD risk reduction, are applicable to most
patients, appropriately target both cerebrovascular and cardi-
ovascular risk, and more accurately identify those at higher
risk. The Expert Panel is clear in stating that these guidelines
are more limited in scope and focus than previous lipid guide-
lines and are not meant to be a comprehensive approach to
lipid management. However, as a scientific community that
may have been expecting the next iteration of “lipid guidelines”
or “ATP IV,” it seems we are still coming to terms with the
more streamlined 2013 ACC/AHA guideline. With controversy
may come a hesitation to implement appropriate recommen-
dations, so in this review, we will summarize the 2013 ACC/
AHA guidelines, discuss the major paradigm shifts as we see
them, and highlight the need for the appropriate implementa-
tion of ASCVD risk assessment and reduction for all patients.
We put this discussion in context with recommendations from
other national and international societies, whose recommen-
dations are complementary and in some cases more compre-
hensive, especially for those patients for whom
recommendations are still unclear after the implementation
of the 2013 ACC/AHA guideline recommendations.
2013 ACC/AHA cholesterol guideline
The 2013 ACC/AHA cholesterol guideline was released in
November 2013 and, in contrast to ATP III, is purposely more
limited and not intended to serve as a comprehensive
approach to lipid management nor is it a replacement for
ATP III [1,2]. Instead, the focus is on the role of cholesterol
treatment in ASCVD risk reduction. In addition, this guideline
was based solely on high-quality evidence from RCTs, sys-
tematic reviews, and meta-analyses of RCTs. The literature
search was guided by clinical questions that were developed
by the Expert Panel. In areas where the data were less robust
or the conclusions were less clear, the Expert Panel refrained
from making recommendations. The basis for the guideline
was to identify those most likely to benefit from cholesterol-
Table 1 – Summary of key recommendations from the 2013 ACC/AHA cholesterol guideline [1].
Groups most likely to benefit from statin therapy
Patients with clinical ASCVD
Low-density lipoprotein cholesterol (LDL-C) Z190 mg/dL
Diabetics aged 40–75 years with LDL-C 70–189 mg/dL and without
clinical ASCVD
Non-diabetics aged 40–75 years with an estimated 10-year ASCVD risk
Z7.5%
ME D I C I N E 25 (2015) 340–347 341
lowering therapy in order to reduce ASCVD, which includes
coronary heart disease (CHD), stroke, and peripheral arterial
disease (PAD). Prior to and along with medical therapy for all
patients, the guideline emphasizes the importance of lifestyle
modification, including a heart-healthy diet, exercise, avoid-
ance of tobacco products, and maintaining a healthy weight,
for which a separate guideline was co-released [6].
Based on their review of the evidence, the Expert Panel
identified four major groups most likely to benefit from statin
therapy: (1) secondary prevention in patients with clinical
ASCVD, (2) primary prevention in patients with primary
elevations of low-density lipoprotein cholesterol (LDL-C)
4190 mg/dL, (3) primary prevention in diabetics aged 40–75
years with LDL-C 70–189 mg/dL and without clinical ASCVD,
or (4) primary prevention in non-diabetics aged 40–75 years
with an estimated 10-year ASCVD risk Z7.5% as determined
by the new Pooled Cohort Equations [7] and LDL-C 70–189 mg/dL
(Table 1). High-intensity statin therapy is recommended for
those with clinical ASCVD, as well as those with significant
primary elevations in LDL-C, which are likely due to a genetic
cholesterol disorder such as familial hypercholesterolemia.
For diabetics, at least moderate-intensity statin should be
considered, and high-intensity statin is recommended if the
estimated 10-year risk using the Pooled Cohort Equations is
Z7.5%. For other primary prevention patients with high
10-year risk, a moderate or high-intensity statin is recom-
mended, but only after an individualized clinician–patient
discussion regarding risks and benefits of statin therapy. If
the decision is still unclear, additional factors may be con-
sidered to aid in the risk assessment including LDL-C
Z160 mg/dL, family history of premature ASCVD, high-
sensitivity CRP Z2.0 mg/L, coronary artery calcium score
Z300 Agatston units, ankle brachial index o0.9, or a high
lifetime risk of ASCVD. Excluded from these recommenda-
tions are those patients with NYHA class II–IV and those on
hemodialysis, as the evidence was inconclusive as to the
benefit of cholesterol treatment in these groups.
Though specific lipid levels are no longer targeted, the
Expert Panel recommends a baseline lipid panel prior to
statin initiation, a follow-up lipid panel within 4–12 weeks
after initiation, and then every 3–12 months thereafter to
monitor adherence. It is expected that high-intensity statin
therapy will reduce LDL-C by approximately 50% and
moderate-intensity statin by 30–50% from baseline. Safety
measurements should be measured as clinically indicated.
If the LDL-C response is less than expected, it is recom-
mended that medication adherence and lifestyle changes be
reinforced. If a higher risk patient is unable to tolerate
moderate- or high-intensity stain therapy, lower dose statin
Recommended statin intensity
High intensity
High intensity
Z7.5% 10-year risk—high intensity
o 7.5% 10-year risk—moderate intensity
Moderate to high intensity if appropriate after clinician–patient
discussion
342 T R E N D S I N C A R D I O V A S C U L A R
or the addition of nonstatin cholesterol-lowering drugs could
be considered if the potential benefit for ASCVD risk reduc-
tion outweighs the potential for adverse effects.
Paradigm shift: Targeting ASCVD risk instead of LDL-C levels
Based on their review of the literature, the Expert Panel
concluded that there was insufficient evidence to support
titration of cholesterol-lowering therapy to reach specific
LDL-C or non-high-density lipoprotein-cholesterol (non-
HDL-C) levels. Therefore, the current guidelines have refo-
cused the target of therapy from specific LDL-C levels to
overall ASCVD risk reduction, with LDL-C monitoring as an
important component of ensuring appropriate response and
adherence to statin therapy. This is in stark contrast to other
published guidelines, including the prior United States cho-
lesterol management guidelines, ATP III, as well as recent
guidelines from other societies including the European Soci-
ety of Cardiology/European Atherosclerosis Society (ESC/EAS),
Canadian Cardiovascular Society (CCS), and the International
Atherosclerosis Society (IAS) [2,8–10]. This paradigm shift has
been the most radical change, and one that has been the
center of several commentaries [3,4,11].
The removal of LDL treatment targets has the potential to
shift the focus away from LDL-C and other atherogenic
lipoproteins, or the “LDL hypothesis,” which was promoted
by ATP III and is supported by a significant body of evidence
for patients at all levels of risk [2,12–14]. Instead of “lower is
better” for LDL-C, the focus is now on matching statin
intensity to ASCVD risk levels, almost independent of LDL-C
levels, although percent LDL-C reduction is used as a marker
for successful therapy. The basis of this change was a strict
interpretation of the RCTs and other studies that were used
in the guideline creation. Interestingly, many of these same
RCTs were those that informed the previous iterations and
update of ATP III in which lower and lower achieved LDL-C
levels were found to be associated with lower ASCVD event
rates [12]. However, the Expert Panel concluded that because
only fixed doses of cholesterol-lowering drugs have been
evaluated in multiple RCTs for ASCVD risk reduction, not
treating to specific lipid levels, there was insufficient evi-
dence to support titrating cholesterol-lowering drug therapy
to achieve a target LDL-C or non-HDL-C level. In support of
this approach, the Expert Panel also notes that the approach
of either a level based or “lowest is best” strategy does not
take into account the increased risk of adverse effects of
combination therapy when additional agents are added to
statin therapy. In addition, the Expert Panel notes that if
patients meet a targeted cholesterol level on low-intensity
statin therapy, they are being denied the proven benefit of
higher potency statins. This is especially important for
secondary prevention of ASCVD in patients with baseline
lipids that may be at or below “goal” prior to treatment, or are
at “goal” on low-intensity statin therapy. In these cases,
intensification of statin therapy would be recommended,
and response should be monitored based on current treat-
ment levels, especially if pretreatment values are not avail-
able. Proponents of reinstating specific LDL-C levels as a goal
argue that there are both RCT data as well as strong
ME D I C I N E 25 (2015) 340–347
observational data to support targeting lower levels of LDL-C
and that such a dogmatic approach to interpreting the
evidence may be short-sighted [11,14,15]. For patients at all
levels of risk, and especially the highest risk patients, there is
strong and consistent evidence that supports treating to a
lower LDL-C goal [13,15–17]. The lack of specific LDL-C targets
is also potentially problematic for patients who have been on
statin therapy and their pretreatment lipids are unknown,
thereby making an assessment of the expected response to
statin therapy difficult. As others have recently proposed, for
a patient with established ASCVD who does not achieve an
optimal LDL-C level, a “discussion of residual risk” could take
place in which intensification of lifestyle therapy or addi-
tional drug therapy would be discussed [3].
Paradigm shift: Stronger focus on statins
The 2013 ACC/AHA guideline recommends using evidence-
based fixed dose of statins as first line for all patients with
elevated ASCVD and does not recommend the routine use of
nonstatin agents for most patients. Although not a major
shift from ATP III, which also recommended statin therapy as
first-line LDL-C reduction therapy, there is a renewed focus
on maximizing statin therapy and reserving nonstatin agents
as adjuncts or alternatives only when statins are contra-
indicated or not tolerated. The basis for this recommendation
is two-fold. First, the Expert Panel concluded that based on
available high-quality evidence, additional reduction in
ASCVD was not demonstrated when nonstatin drugs were
added onto a baseline of statin therapy. Second, there is a
significantly greater potential for adverse effects when
nonstatin agents are combined with statin therapy. The
recent studies evaluating niacin in addition to statin ther-
apy in patients already at low LDL-C levels support these
two points [18,19]. The guideline does allow for the consid-
eration of nonstatin agents in high-risk patients who have a
less-than-anticipated response to statin therapy or are statin
intolerant. The Expert Panel also recognizes that addition of
nonstatin drugs may be necessary in patients with very high
primary LDL-C levels, such as those patients with familial
hypercholesterolemia, which is an important distinction [1].
To guide clinicians, the published document includes a full
table with recommendations on nonstatin safety [1].
In simplifying the treatment approach and emphasizing
statins as the primary medical therapy, the new guidelines
will hopefully improve compliance and reduce potential
adverse effects of combination therapy. In addition, data is
lacking on the benefit of achieving a very low LDL-C level
with a combination of nonstatin agents. Similar to the
removal of lipoprotein targets, critics argue that this para-
digm shift also takes the focus away from the “LDL hypoth-
esis” and the body of evidence demonstrating that a lower
LDL-C leads to decreased cardiovascular events. As one
author ponders: “My suspicion, … was that dropping targets
allowed the panel to avoid a serious discussion of nonstatin
agents” [11]. Without consideration of target lipoprotein
levels, it becomes difficult to define residual risk while on
statin therapy and to determine which patients will benefit
most from nonstatin agents.
 T R E N D S I N C A R D I O V A S C U L A R
Paradigm shift: Use of a new risk calculator
Although not the most radical paradigm shift of the 2013
guideline, the inclusion of a new risk calculator has generated
significant debate and discussion. The decision to transition
from the previously used Framingham Risk Score (FRS) to a
new tool was based on well-known limitations of the FRS.
These limitations include the fact that the FRS was derived
exclusively from a white population and only included hard
CHD end points [myocardial infarction (MI) and CHD death].
In addition, the FRS tends to underestimate risk, especially in
women [20]. Replacing the FRS in the 2013 ACC/AHA choles-
terol guideline is the new Pooled Cohort Equations, which
was derived from four longitudinal NHLBI-funded commun-
ity-based epidemiological cohort studies with at least 12
years of follow-up that are broadly representative of both
the white and African American populations in the United
States [7]. The Expert Work Group for the separate Guideline
on the Assessment of Cardiovascular Risk used state-of-the-
art statistical methods to derive and internally validate the
Pooled Cohort Equations, which provide sex- and race-
specific estimates of the 10-year risk of ASCVD end points
(nonfatal MI, CHD death, or stroke) for white and African
American men and women 40–79 years of age [7]. End points
influenced by provider preferences (e.g., elective revasculari-
zations) and end points with poor reliability (e.g., angina and
heart failure) were purposefully excluded. The data required
for the risk calculation are meant to be easily collected by
primary care providers and implemented in routine clinical
practice. Web-based applications are available for use, and
the equations have been published for those who wish to
program them into electronic medical records. Variables used
to determine risk are similar to those included in the FRS and
include the following: age, gender, race (a new addition),
treated or untreated systolic blood pressure (SBP), total
cholesterol, HDL-C, smoking status, and diabetes (new addi-
tion). Numerous other potential risk markers were considered
for inclusion in the calculator; however, no additional utility
was demonstrated, or data were insufficient to determine
their additional value.
Based on the patient population in the derivation cohorts,
the risk calculator is designed for African American and non-
Hispanic whites aged 40–79 years, though the authors do give
a class IB recommendation for its use in other populations.
The Expert Work Group notes that when compared with non-
Hispanic whites, the estimated 10-year risk of ASCVD is
generally lower in Hispanic-American and Asian-American
populations and higher in American-Indian populations. For
those aged 20–59 years, the risk calculator also calculates
lifetime risk, which can differ substantially from the 10-year,
i.e., short-term risk. However, evidence was insufficient for a
specific lifetime risk cut point to guide pharmacological
therapy decisions, and it is recommended that it be used
solely to motivate therapeutic lifestyle change.
The new risk calculator is an improvement over the
previously used FRS in that it is more current, applicable to
both whites and African Americans, includes stroke as a
primary end point, and includes lifetime risk as a starting
point for discussions of lifestyle modification in younger
patients. However, critics of the new risk calculator cite that
ME D I C I N E 25 (2015) 340–347 343
it systematically overestimates risk [5]. The Work Group
evaluated the performance of the algorithms in two external
cohorts with short-term follow-up, which were chosen for
their large size, contemporary nature, and comparability of
end points, and also found overestimation of risk [7]. How-
ever, in the more recently published external validation study
using longer term follow-up from one of these cohorts, the
Reasons for Geographic and Racial Differences in Stroke
(REGARDS) study, the differences in the observed and pre-
dicted risks were small when the study population was
limited to participants without diabetes, not taking statins,
and with LDL-C of 70–189 mg/dL, the population for which the
risk calculator is designed to be used to trigger a risk
discussion and possible statin prescription [21]. Possible
reasons for the overestimation of risk have been proposed
and include underascertainment of events in the validation
cohorts compared with the derivation cohorts, high preva-
lence of statin use in contemporary populations that would
lower observed risk, and increasing the use of revasculariza-
tion procedures that could alter future event rates [22].
Other possible shortcomings of the new risk calculator are
that it has abandoned the concept of “vascular age,” which
can be a very useful counseling tool for helping patients
understand their risk level [23]. Finally, a potential pitfall of
using this or any other risk calculator is that calculation of 10-
year risk is not recommended until the age of 40 years based
on the limitations of the data that was used to create the
algorithms. In younger patients, lifetime risk can be calcu-
lated but is recommended only to guide lifestyle recommen-
dations not pharmacotherapy. However, the substrate for
ASCVD, namely atherosclerotic plaque, begins early in life,
and as some have proposed, early and aggressive treatment
should be considered for the goal of atherosclerosis regres-
sion [24]. Such novel concepts are intriguing but will need
future research.
Paradigm shift: Lowering the threshold for statin therapy
Along with the new Pooled Cohort Equations, the 2013 ACC/
AHA guidelines have lowered the 10-year risk threshold for
consideration of initiation of statin therapy from Z10% to
Z7.5%, noting that they have found statin therapy is effective
and cost-effective for preventing ASCVD in study populations
with at least this level of risk, and that the number needed to
treat for benefit outweighs the number needed to harm due
to increased incidence of diabetes [1]. When compared to the
FRS, the authors cite that with the new guidelines a similar
percentage of the population (31.9% vs. 32.9%) would fall into
the high-risk category.
Again, the main criticism is that the overestimation of risk
along with the new risk cut point will lead to a significant
increase in the number of statin users [5]. In addition, no trial
of statin therapy to date has used a global risk prediction
score as an enrollment criterion [5]. As the algorithm is
heavily driven by age, another quandary is what to do in
healthy patients without risk factors who exceed the 7.5%
threshold based on age alone. For example, at optimal levels
of cholesterol and blood pressure, most non-smoking, non-
diabetic men will exceed the 7.5% 10-year risk threshold in
their early to mid-60s and women right at 70 years of age [25].
 344
Table 2 – Comparison of cholesterol treatment guidelines and expert opinion statements from various national and international societies.

2013 ACC/AHA[1] ATP III (2001 and 2004 IAS (2014)[10] ESC/EAS (2011)[8] CCS (2012)[9] NLA (2014)[26]
update)[2,12]

Risk Assessment Pooled Cohort Equations Framingham þ history of Framingham, The Systematic Coronary Framingham Framingham
Tool CHD or risk equivalents Cardiovascular Risk Evaluation
and counting of major Lifetime Risk Pooling (SCORE) System
risk factors Project, and QRISK
Primary Risk 10 year 10 year Lifetime 10 year 10 year 10 year
Outlook
Risk Levels High risk and likely to benefit High risk: CHD or CHD Diagnosed ASCVD Very high risk: High risk: 420% 10 Very high risk: ASCVD,
from treatment: equivalents*, or 420% ASCVD, DM, CKD, year risk, ASCVD, DM þ Z2 other major

T
10 year Framingham High risk: risk of 410% 10 year risk AAA, DM, CKD, ASCVD risk factors** or

R E N D S I N
 Clinical ASCVD risk ASCVD Z 45%, DM High risk: 5-10% 10 high risk Htn end-organ damage
 Primary elevations of LDL–C Moderate risk: Z2 major and other risk year risk, FH Intermediate risk: High risk: Z3 major
Z190 mg/dl, risk factors *** or 10- factors, FH Moderate risk: Z1% 10-19% 10 year risk ASCVD risk factors,
 Diabetes aged 40 to 75 years 20% 10 year risk Moderately high risk: and r5% 10 year risk DM with r 1 risk

C
with LDL–C 70 to189 mg/dl Low risk r1 major Risk of ASCVD 30-45%, factor, CKD 3-4,

and without clinical ASCVD
 LDL–C 70 to189 mg/dl and
estimated 10-year ASCVD
risk Z7.5%
A R D I O V A S C U L A R
risk factor DM without other risk LDLZ190 mg/dl,
factors, CKD, quantitative risk
metabolic syndrome scoring reaching high-
Moderate risk: Risk for risk threshold
ASCVD of 15-29% Moderate risk: 2 major
ASCVD risk factors
Low risk: 0-1 major
ASCVD risk factors

ME
D I C I N E
Target of ASCVD risk 1. LDL-C 1. LDL-C LDL-C 1. LDL-C 1. Non-HDL –C
Therapy 2. Non-HDL-C 2. Non-HDL-C 2. Non-HDL-C, apoB 2. LDL-C

ASCVD: LDL-C o 70 mg/ High risk: LDL o 2.0

Treatment Goal High intensity statin:
clinical ASCVD , LDL Z190
mg/dl, or DM with
ASCVDZ7.5%
Moderate to high intensity
statin: lower risk diabetics
and non-diabetics with
ASCVD Z7.5%
Initial Drug Moderate or high intensity
Therapy statin
Consider Only if statins not tolerated,
Additional or if 450% reduction not
Nonstatin achieved in patients with
Agents LDLZ190 mg/dl at baseline
High risk :LDLo 100,
optional o70 mg/dl dl and non-HDL-C o
Moderate risk: LDL 100 mg/dl
o130 mg/dl, with  Goal LDL o100 mg/dl
option for o 100 mg/dl for all patients at risk
if moderately high risk  Statin therapy only for
Low risk: LDLo160 mg/ those at high or
dl moderately high risk,
or those at lower risk
with high or very high
LDL-C
Statin therapy Statin therapy
If goals not met If goals not met
25 (2015) 340–347
Very high risk: LDLo Very high risk: Non-
70 mg/dl mmol/l (77mg/dl), HDL-C o100, mg/dl,
High risk: LDL can consider o 1.8 LDL-C o70 mg/dl
o100 mg/dl mmol/l (70 mg/dl) High risk: Non-HDL-C
Moderate risk: LDLo Intermediate risk: o130, mg/dl, LDL-C
115 mg/dl LDL o 2.0 mmol/l o100 mg/dl
Statin therapy Statin therapy Moderate to high
intensity statin
If goals not met If goals not met If goals not met

Abbreviations not used in main text: AAA, abdominal aortic aneurysm; apoB, apolipoprotein B; CKD, chronic kidney disease; DM, diabetes; FH, familial hypercholesterolemia; Htn, hypertension.
n
CHD, symptomatic carotid disease, PAD, diabetes, AAA.
nn
Age (male 445 years, female 455 years), family history of early CHD (male o55 years, female o65 years), cigarette smoking, hypertension, and low HDL-C (male o40 mg/dl, female o50 mg/dl).
nnn
Smoking, Htn, HDL-C o40 mg/dl, family history of premature coronary artery disease (o55 years in male, o65 years in female), age (male 445 years, women 455 years).
 T R E N D S I N C A R D I O V A S C U L A R ME D I C I N E 25 (2015) 340–347 345

Others would argue that there are still patients who would
benefit from statin therapy that we are not targeting, as their
short-term risk falls below the 7.5% threshold. In the 2012
Cholesterol Treatment Trialists' meta-analysis of statin ben-
efit in patients at low risk for vascular events, there was a
significant decrease in major coronary and vascular events by
about one-fifth per 1 mmol/L (38.6 mg/dL) reduction in LDL
cholesterol, and additional reductions in LDL-C obtained with
more intensive statin regimens further reduced the incidence
of these major vascular events [14]. For all risk levels, the
benefit outweighed the risk of adverse events due to statin
therapy [14].
However, data will continue to evolve, which is why the
Expert Panel emphasizes that the estimation of risk is a
starting point for an ASCVD risk discussion and that clinical
judgment must always prevail in the decision to initiate any
therapy.
Recommendations from other societies
Many other guidelines and expert opinions exist for lipid
management including ATP III, IAS, EAS, and CCS, along with
many others. In addition, the National Lipid Association
(NLA) has just released recommendations for patient-
centered management of dyslipidemia [26] (Table 2). Similar
to the 2013 ACC/AHA guideline, patients are placed into risk
categories based on history of ASCVD and risk factors widely
accepted to lead to the development of ASCVD. Lifestyle
modification is universally a cornerstone of therapy, and
statins are agreed upon as first-line medical therapy. Most
importantly, all of these recommendations recognize that
ASCVD risk reduction is a complex patient-centered decision,
and that they are meant to be a starting point for a discussion
about overall risk reduction and the risks and benefits of
medical therapy to help modify this risk, and are not meant
to be rigid treatment algorithms.
There is variability among the various recommendations in
the preferred method of calculating risk and what the target
lipoproteins should be. However, in contrast to the 2013 ACC/
AHA guideline, they all recommend treating to a target
lipoprotein level. In distinction to the 2013 ACC/AHA guide-
line, most of these documents are meant to be a more
comprehensive approach to dyslipidemia management and
give recommendations on a more detailed scale, including
more information about special patient populations that are
not specifically addressed by the 2013 ACC/AHA guideline.
Guideline implementation for ASCVD risk
reduction
Despite the controversies, the 2013 ACC/AHA guidelines
along with the updated risk calculator have introduced
several major paradigm shifts that make the choice of
moderate- or high-intensity statin an easier and a more
consistent choice for clinicians, and will ensure adequate
statin intensity for the highest risk patients regardless of
baseline LDL-C (Table 3). In many patients, this shift in focus
will ultimately avoid or minimize the adverse effects of
polypharmacy and allow clinicians the freedom to tailor
therapy to patient-specific factors without an LDL-C level
completely driving clinical decisions. The new risk calculator
is an improvement over the previously used Framingham
calculator in that it is more current, applicable to both whites
and African Americans, includes stroke as a primary end
point, and includes lifetime risk as a starting point for
lifestyle modification in younger patients. The lower risk
cut point will help identify more patients potentially at risk
and will hopefully lead to more patient-provider discussions
about lifestyle modification and the potential benefits vs.
risks of statin therapy. Though risk may be overestimated in
some groups, this seems to be more dramatic in higher risk
groups in whom the decision to initiate statin therapy is more
straightforward [21].
Though the changes are substantial, they are grounded in
high-quality evidence and have the potential to further
reduce ASCVD but only if widely adopted by the medical
community. To date, there has been no formal implementa-
tion plan put forth by the ACC or AHA, although web-based
and smart phone tools such as the ASCVD risk calculator are
readily available, free, and easy to implement in clinical
practice. There are also informational brochures and tools
on the AHA website that are directed toward patients,
which, if used, may help to engage patients and inform
discussions with providers. We hope that both clinicians
and patients can understand the rationale for the guidelines
and the need for implementation. We recommend that

Table 3 – Pros and cons of several of the major paradigm shifts of the 2013 ACC/AHA cholesterol guidelines.

Major paradigm shift Pro Con

Targeting ASCVD risk instead of LDL-C
levels
Emphasis on statin therapy and
avoidance of nonstatin agents in
most patients
Use of a new risk calculator
Lower risk calculator cut point for
statin therapy initiation
Will avoid undertreatment of high-risk
patients with already low levels of LDL
Simple to implement
Avoid adverse effects of polypharmacy
Lack of proven benefit at this time
More current and applicable to African
American and white populations
Includes stroke in risk estimation
Identifies a subset of patients not previously
identified that may benefit from statin
therapy
May undertreat residual risk in patients with
elevated LDL-C despite recommended statin
intensity
May undertreat residual risk in patients with
elevated LDL-C despite recommended statin
intensity
May overestimate risk in some groups
The number of patients on statin therapy,
especially based on age alone, may be
excessive
346 T R E N D S I N C A R D I O V A S C U L A R
clinicians employ the 2013 ACC/AHA guidelines as written,
yet encourage the complementary use of one or more of the
more comprehensive dyslipidemia guidelines for further
guidance of screening, special patient populations, and for
possibly choosing a goal lipoprotein level for the highest risk
patients. We believe that the data supports targeting a low
LDL-C [17], and based on currently available data, we agree
with other societies that an LDL-C o70 mg/dL and/or non-
HDL-C o 100 mg/dL is a reasonable goal for those with
clinical ASCVD. In those who do not achieve a desired LDL-
C level, even if they have had the anticipated response to
statin therapy, a “residual risk discussion” with the patient
should occur, perhaps with a specialist in lipid management
to help “fine tune” management using the more compre-
hensive lipid management recommendations. Most impor-
tantly, it is crucial for clinicians to remember that the risk
calculator as well as the guidelines themselves should all be
used to engage patients in a comprehensive discussion of
ASCVD risk and that this discussion be used to guide
therapy. Though statins are generally well-tolerated and
safe, they may pose risk, especially in the elderly, so clinical
judgment is critical.
Conclusions
The major paradigm shifts that the 2013 ACC/AHA guidelines
have introduced are grounded in the highest quality evidence
and will help clinicians move toward a more patient-centered
approach in preventing ASCVD. They utilize a simple and
acceptably accurate risk assessment method, and, by focus-
ing on evidence-based high-potency statin therapy as
opposed to specific LDL-C goals, they simultaneously help
prevent undertreatment of higher risk patients and overtreat-
ment of lower risk patients. Lipoprotein levels, however,
should not be discounted, and in higher risk patients, LDL-C
goals should still be considered. The 2013 ACC/AHA guide-
lines are focused on ASCVD risk reduction, and the comple-
mentary utilization of other societies recommendations will
serve as essential complements. By using these documents in
series, starting with the 2013 ACC/AHA guideline, there will
be a higher likelihood of patients being started on the most
appropriate, effective, and evidence-driven pharmacotherapy
available at this time, i.e., statins.
Overall, we see the 2013 ACC/AHA cholesterol guideline as
a bold step forward in the landscape of ASCVD risk reduction,
and we hope that these recommendations continue to evolve
as new evidence emerges and when new therapies become
available. For example, looking ahead to the development of
more potent LDL-C-lowering drugs such as proprotein con-
vertase subtilisin/kexin type 9 (PCSK9) inhibitors that will
allow attainment of even lower LDL-C levels, LDL-C or other
lipoprotein targets may be helpful in deciding which patients
have the potential to benefit most from these novel treat-
ments [27]. In addition, we look forward to data evaluating
the impact of targeting risk according to this guideline.
Finally, we hope that clinicians will adopt and implement
the guideline using their best clinical judgment in order to
reduce ASCVD risk across all populations.
ME D I C I N E 25 (2015) 340–347
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