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THE ABC’S OF THE
AHA/ACC Ischemic Heart
Disease GUIDELINES
Roger S. Blumenthal, MD
Professor of Medicine
Director, The Johns Hopkins Ciccarone Center
For The Prevention of Heart Disease
DEFINITION
PRIMARY Prevention: Modification of risk factors or
prevent their development to prevent or delay the onset of
CHD.
SECONDARY Prevention: Initiation of Rx to reduce
recurrent CHD events in patients with CHD.
PRIMARY AND A HALF Prevention*: As individuals with
subclinical CHD are identified, the distinction between
primary and secondary prevention becomes blurred.
CHD=Coronary heart disease
*Celermajer DS. JACC 2005;45:1994-6
ASPIRIN RECOMMENDATIONS
SECONDARY PREVENTION
I
IIa
IIb
III
Aspirin (75-325 mg daily) in those with
known CHD or carotid artery or leg artery
narrowings due to plaque.
IIa
IIb
III
Aspirin (100-325 mg daily) in those that have
undergone CABG surgery*.
A
I
B
CABG=Coronary artery bypass graft, CHD=Coronary
heart disease
*To be administered within the first 48 hours after
surgery in order to reduce the risk of saphenous vein
graft failure. Doses >162 mg/day may be continued for
up to one year.
CLOPIDOGREL EVIDENCE: SECONDARY PREVENTION
CLOPIDOGREL IN UNSTABLE ANGINA TO PREVENT RECURRENT
EVENTS (CURE) TRIAL
RATE OF DEATH,
MYOCARDIAL
INFARCTION, OR STROKE
12,562 patients with a NSTE-ACS randomized to daily aspirin (75-325 mg)
or clopidogrel (300 mg load, 75 mg thereafter) plus aspirin for 9 months
ASPIRIN + CLOPIDOGREL
ASPIRIN + PLACEBO
P<0.001
0
3
6
9
MONTHS OF FOLLOW UP
DAP=Dual antiplatelet therapy, NSTE-ACS=Non STsegment elevation acute coronary syndrome
The CURE Trial Investigators. NEJM. 2001;345:494-502
12
ACE INHIBITOR RECOMMENDATIONS
SECONDARY PREVENTION
I
IIa
IIb
III
IIa
IIb
III
A
I
B
An ACE inhibitor in those following a MI, regardless of
EF or in those with CAD* along with hypertension
(SBP >120 mmHg), LVSD (EF <0.40), heart failure,
DM, or CKD.
Optional use of an ACE inhibitor in those with low risk
CAD*, well controlled CV risk factors, a normal EF,
and successful revascularization.
ACE=Angiotensin converting enzyme, CAD=Coronary artery disease,
CKD=Chronic kidney disease, CV=Cardiovascular, DM=Diabetes
mellitus, EF=Ejection fraction, LVSD=Left ventricular systolic
dysfunction, MI=Myocardial infarction, SBP=Systolic blood pressure
*Defined by previous MI or angiographically significant CAD.
ACE INHIBITOR EVIDENCE: SECONDARY PREVENTION
HEART OUTCOMES PREVENTION AND EVALUATION (HOPE)
STUDY
CV DEATH, MI,
OR STROKE (%)
9,297 patients with DM or vascular disease plus one additional CV risk factor, but
without HF or known LVSD randomized to ramipril (10 mg) or placebo for 5 years
0.20
RAMIPRIL
0.15
PLACEBO
0.10
0.05
22% RRR, P<0.001
0.00
0
500
1000
DAYS OF FOLLOW-UP
ACE-I reduce CV events in high-risk individuals
ACE-I=Angiotensin converting enzyme inhibitors, DM=Diabetes mellitus,
CV=Cardiovascular, HF=Heart failure, LVSD=Left ventricular systolic
dysfunction, MI=Myocardial infarction
HOPE Investigators. NEJM 2000;342:145-153
1500
PROBABILITY OF EVENT
ACE INHIBITOR EVIDENCE: SECONDARY PREVENTION
0.4
SAVE
AIRE
TRACE
Radionuclid
e
EF  40%
Clinical and/or
radiographic
signs of HF
Echocardiogram
EF  35%
Placebo
0.35
ACE-I
0.3
0.25
0.2
0.15
0.1
OR: 0.74 (0.66–0.83)
0.05
0
0
1
2
3
4
YEARS
ACE-I provide substantial benefit in post-MI LVSD
ACE-I=Angiotensin converting enzyme inhibitors, LVSD=Left
ventricular systolic dysfunction, MI=Myocardial infarction, OR=Odds
ratio
Flather MD, et al. Lancet. 2000;355:1575–1581
BLOOD PRESSURE: LOWER IS BETTER
Age at Risk (Y)
80-89
256
70-79
128
60-69
64
50-59
32
40-49
16
8
4
2
1
Ischemic Heart Disease Mortality
Ischemic Heart Disease Mortality
Ischemic Heart Disease Mortality
256
Age at Risk (Y)
80-89
128
70-79
64
60-69
32
50-59
16
40-49
0
8
4
2
1
0
120 140 160 180
Usual Systolic BP (mm Hg)
BP=Blood pressure
Prospective Studies Collaboration. Lancet. 2002;360:1903-1913
70 80 90 100 110
Usual Diastolic BP (mm Hg)
BLOOD PRESSURE RECOMMENDATIONS
SECONDARY PREVENTION
I
IIa
IIb
III
Initiation or maintenance of lifestyle modification in
those with a BP >120/80 mmHg.
B
I
A
IIa
IIb
III
Use of an ACE inhibitor and/or b-blocker in
those with a BP >140/90 mmHg*. Other drugs
(i.e., thiazide diuretics) should be added in order
to achieve the desired BP.
ACE=Angiotensin converting enzyme, BP=Blood pressure, CKD=Chronic kidney
disease, DM=Diabetes mellitus
*A BP >130/80 mmHg should be used for individuals with CKD or DM
BLOOD PRESSURE EVIDENCE: SECONDARY PREVENTION
COMPARISON OF AMLODIPINE VS ENALAPRIL TO LIMIT OCCURRENCES
OF THROMBOSIS (CAMELOT) TRIAL
CV event rate*
1,991 patients with CAD and a DBP <100 mmHg randomized to amloidipine (10
mg), enalapril (20 mg), or placebo for 2 years
0.25
130/78
124/77
125/77
Placebo
Enalapril
Amlodipine
0.20
0.15
Follow-up BP
(mmHg)
0.10
0.05
0
0
6
12
18
24
Months
A BP <130/80 mmHg is associated with fewer CV events
BP=Blood pressure, CAD=Coronary artery disease, CV=Cardiovascular, DBP=Diastolic blood pressure,
HF=Heart failure, MI=Myocardial infarction, PAD=Peripheral arterial disease, TIA=Transient ischemic attack
*Includes CV death, MI, cardiac arrest, coronary revascularization,
hospitalization for HF or angina pectoris, stroke, TIA, development of
PAD
Nissen S et al. JAMA 2004;292:2217-26.
b-BLOCKER RECOMMENDATIONS*
SECONDARY PREVENTION
A b-blocker in all patients following a MI.
I
IIa
IIb
III
A
I
A beta-blocker in all patients with LVSD.
IIa
C
IIb
III
A b-blocker in those with other forms of CV
disease or DM, unless contraindicated.
CV=Cardiovascular, DM=Diabetes mellitus, LVSD=Left ventricular systolic dysfunction, MI=Myocardial
infarction
*Relative contraindications include asthma, chronic obstructive pulmonary disease, insulin
dependent diabetes mellitus, severe peripheral arterial disease, and a PR interval >0.24
seconds.
CHOLESTEROL MANAGEMENT GUIDELINES
SECONDARY PREVENTION
I
IIa
IIb
III
B
I
Restriction of saturated fat (<7% of total calories)
and cholesterol (<200 mg/day) in all patients.
Promotion of daily physical activity and weight
management in all patients.
IIa
IIb
B
III
Increase in w-3 fatty acid consumption in all
patients.
LDL-C=Low density lipoprotein cholesterol
CHOLESTEROL MANAGEMENT GUIDELINES (CONTINUED)
SECONDARY PREVENTION
I
IIa
IIb
III
IIa
IIb
III
A
I
B
Initiation or intensification of LDL-C lowering drug
therapy in those with a baseline or on-treatment LDL-C
level >100 mg/dl.
Initiation of LDL-C lowering drug therapy in those with
a baseline LDL-C level <100 mg/dl based on clinical
judgment.
LDL-C=Low density lipoprotein cholesterol
CHOLESTEROL MANAGEMENT GUIDELINES (CONTINUED)
GOALS
As set forth by the
Adult Treatment
Panel III (ATP III)
National Cholesterol
Education Program
(NCEP)
RECOMMENDATIONS
Obtain a fasting lipid profile in all patients. For those with a
myocardial infarction, a fasting lipid profile should be
obtained within 24 hrs of admission.
Start therapeutic lifestyle changes in all patients, including:
• Reduced intakes of saturated fats (<7% of total
calories) and cholesterol (<200 mg/day)
• Addition of plant stanols/sterols (2 g/day) and viscous
fiber (10-25 g/day) to enhance LDL-C lowering
• Weight reduction
• Increased physical activity
Expert Panel on Detection, Evaluation, and Treatment of High Blood
Cholesterol in Adults. JAMA 2001;285:2486.
ATP III LDL-C GOALS AND CUT-POINTS FOR DRUG THERAPY
Risk Category
LDL-C Goal
High risk:
CHD or CHD risk equivalents
(10-year risk >20%)
<100 mg/dL
(optional goal:
<70 mg/dL)
Moderately high risk:
2+ risk factors*
(10-year risk 10% to 20%)
Moderate risk:
2+ risk factors*
(10 year risk <10%)
Lower risk:
0-1 risk factor*
Initiate TLC
Consider
Drug Therapy
100 mg/dL
>100 mg/dL
(<100 mg/dL: consider drug
options)
<130 mg/dL
(optional goal:
<100 mg/dL)
130 mg/dL
>130 mg/dL
(100-129 mg/dL: consider
drug options)
<130 mg/dL
130 mg/dL
>160 mg/dL
160 mg/dL
>190 mg/dL
(160-189 mg/dL: LDLlowering drug optional)
<160 mg/dL
*Risk factors for cardiovascular disease include: cigarettes smoking, hypertension (blood pressure >140/90 mmHg or on
antihypertensive medication, HDL-C <40 mg/dl (>60 mg/dl is a negative risk factor), family history of premature CHD,
age >45 years in men or >55 years in women.
ATP=Adult Treatment Panel, CHD=Coronary heart disease, LDL-C=Low-density lipoprotein cholesterol,
TLC=Therapeutic lifestyle changes
Grundy, S. et al. Circulation 2004;110:227-39.
PRIMARY THERAPIES TO LOWER LDL-C
Class
Drug(s)
3-Hydroxy-3-Methylglutaryl Coenzyme A
(HMG-CoA) reductase inhibitors [Statins]
Atorvastatin (Lipitor)
Fluvastatin (Lescol XL)
Lovastatin (generic and Mevacor)
Pravastatin (Pravachol)
Rosuvastatin (Crestor)
Simvastatin (Zocor)
Bile acid sequestrants
Cholestyramine (generic and Questran)
Colesevelam (Welchol)
Colestipol (Colestid)
Cholesterol absorption inhibitor
Ezetimibe (Zetia)
Dietary Adjuncts
Soluble fiber
Soy protein
Stanol esters
HMG-COA REDUCTASE INHIBITOR: SECONDARY PREVENTION
PRAVASTATIN OR ATORVASTATIN EVALUATION AND INFECTION
THERAPY (PROVE-IT)—TIMI 22 STUDY
4,162 patients with an ACS randomized to atorvastatin (80 mg) or pravastatin (40
mg) for 24 months
Recurrent MI or
Cardiac Death
30
Atorvastatin
Pravastatin
25
16% RRR
20
15
10
5
P =0.005
0
3
6
9
12
15
18
21
24
27
30
Follow-up (months)
Acute intensive therapy significantly reduces the event rate
ACS=Acute coronary syndrome, CV=Cardiovascular, MI=Myocardial infarction, RRR=Relative
risk reduction
Cannon CP et al. NEJM 2004;350:1495-1504
HMG-COA REDUCTASE INHIBITOR: SECONDARY PREVENTION
SCANDINAVIAN SIMVASTATIN SURVIVAL STUDY (4S)
4,444 patients with angina pectoris or previous MI randomized to simvastatin
(20-40 mg) or placebo for 5.4 years
30% RRR
11.5
Mortality (%)
12
8.2
8
4
P<0.001
0
Placebo
Simvastatin
Statins provide significant benefit in those with average LDL-C levels
MI=Myocardial infarction, RRR=Relative risk reduction
4S Group. Lancet 1994;344:1383–1389
HMG-COA REDUCTASE INHIBITOR: SECONDARY PREVENTION
HEART PROTECTION STUDY (HPS)
20,536 patients with CAD, other occlusive arterial disease, or DM randomized to
simvastatin (40 mg) or placebo for 5.5 years
Event Rate Ratio (95% CI)
Baseline
LDL-C (mg/dL)
Statin
(n = 10,269)
Placebo
(n = 10,267)
<100
282 (16.4%)
358 (21.0%)
100–129
668 (18.9%)
871 (24.7%)
130
1083 (21.6%)
1356 (26.9%)
All patients
2033 (19.8%)
2585 (25.2%)
Statin Better
Statin Worse
0.76 (0.72–0.81)
P<0.0001
0.4
0.6
0.8
1.0
1.2
1.4
Statins provide significant benefit across a broad range of LDL-C levels
CAD=Coronary artery disease, CI=Confidence interval, DM=Diabetes mellitus,
HPS Collaborative Group. Lancet 2002;360:7-22
CIGARETTE SMOKING CESSATION GUIDELINES
GOALS
Complete cessation
No environmental
tobacco smoke exposure
I
B
IIa
IIb
III
RECOMMENDATIONS
Ask about tobacco use at every visit.
In a clear, strong, and personalized manner, advise
the patient to stop smoking.
Urge avoidance of exposure to secondhand smoke at
work and home.
Assess the patient’s willingness to quit smoking.
Develop a plan for smoking cessation and arrange
follow-up.
Provide counseling, pharmacologic therapy, and
referral to formal smoking cessation programs as
indicated.
SMOKING CESSATION PHARMACOTHERAPY*
Side
Effects
Dosage
Duration
Instructions
Seizure disorder
Eating disorder
Taking MAO
inhibitor
Pregnancy
Insomnia
Dry
mouth
150 mg QAM
then
150 mg BID
3 days
Start 1-2 weeks
before quit date.
Take second
dose in early
afternoon or
decrease to 150
mg QAM for
insomnia.
Within 2 weeks
of a MI
Unstable angina
Arrhythmias
Decompensated
heart failure
Skin
reaction
Insomnia
21 mg QAM
14 mg QAM
7 mg QAM
or
15 mg QAM
Agent
Caution
Bupropion
SR
(Zyban®)
Transdermal
Nicotine
Patch**
Maintenance
(8 weeks,
but may be
used up to 6
months)
4 weeks
2 weeks
2 weeks
8 weeks
*Pharmacotherapy combined with behavioral support provides the best success
rate
**Other nicotine replacement therapy options include: nicotine gum, lozenge,
inhaler, nasal spray
Apply to different
hairless site
daily.
Remove before
bed for insomnia.
Start at <15 mg
for <10 cigs/day
SMOKING CESSATION PHARMACOTHERAPY: VARENICLINE
Study 1
p<0.001 for V vs B
p<0.001 for V vs P
Two trials compared treatment with varenicline, a
nicotine acetylcholine receptor agonist, to treatment
with buproprion or placebo.
Study 2
p<0.001 for V vs B
p<0.001 for V vs P
These trials included a total of almost 700
participants. The mean duration of smoking was 25
years.
Varenicline yielded higher rates of smoking
cessation than buproprion or placebo.
JAMA 2006:296:47-55 and JAMA 2006;296:56-63
WEIGHT MANAGEMENT GUIDELINES
GOALS
RECOMMENDATIONS
Calculate BMI* and measure waist
circumference as part of evaluation.
Monitor response of BMI and waist
circumference to therapy.
BMI 18.5 to 24.9 kg/m2
Women: <35 inches
Men: <40 inches
10% weight reduction
within the first year of
therapy
I
IIa
IIb
III
B
I
A
IIa
IIb
III
Start weight management and physical
activity as appropriate.
If BMI and/or waist circumference is above
goal, initiate caloric restriction, measures
to increase caloric expenditure, and
treatment strategies for the metabolic
syndrome.
BMI=Body mass index
*BMI is calculated as the weight in kilograms divided by the body surface area in meters2.
Overweight state is defined by BMI=25-30 kg/m2. Obesity is defined by a BMI >30 kg/m2.
PREVALENCE OF OBESITY IN U.S. ADULTS
1996
1991
2003
% State Population
No Data
Source: CDC Overweight and Obesity
<10%
10%–14%
15%–19%
20%–24%
≥ 25%
CV RISK INCREASES WITH BODY MASS INDEX
Hazard Ratio
Hemorrhagic
Stroke
Ischemic
Stroke
Ischemic Heart
Disease
4.0
4.0
4.0
2.0
2.0
2.0
1.0
1.0
1.0
0.5
0.5
0.5
16 20 24 28 32 36
16 20 24 28 32 36
Body Mass Index (kg/m2)*
CV=Cardiovascular
Body mass index is calculated as the weight in kilograms divided by the body
surface area in meters2.
Mhurchu N et al. Int J Epidemiol 2004;33:751-758
16 20 24 28 32 36
DIABETES MELLITUS GUIDELINES
GOALS
Goal HbA1C <7%
RECOMMENDATIONS
Intensive lifestyle modification to prevent the development
of DM (especially in those with the metabolic syndrome)
Aggressive management of CV risk factors (i.e., tobacco
use, hypertension, dyslipidemia, physical inactivity, and
overweight and obese states)
I
IIa
IIb
III
Hypoglycemic therapy to achieve normal to near normal
fasting plasma glucose as defined by the HbA1C (<7%)
• Weight reduction and exercise
• Oral hypoglycemic agents
• Insulin therapy
B
I
C
IIa
IIb
III
Coordination of diabetic care with the patient’s primary
physician and/or endocrinologist.
CV=Cardiovascular, DM=Diabetes mellitus, HbA1C=Glycosylated hemoglobin
EXERCISE GUIDELINES
GOALS
RECOMMENDATIONS
Minimum: 30 minutes,
5 days per week
Optimal: 30 minutes daily
I
B
IIa
IIb
III
Assess risk, preferably with exercise test, to guide
prescription.
Encourage aerobic activity (e.g., walking, jogging,
cycling) supplemented by an increase in daily
activities (e.g., walking breaks at work, gardening,
household work).
Encourage resistance training (e.g., weight machines,
free weights) 2 days a week (Class IIb, Level C)
Encourage cardiac rehabilitation for patients with
chronic stable angina, recent myocardial infarction,
left ventricular systolic dysfunction, or recent coronary
artery bypass graft surgery.
EJECTION FRACTION GUIDELINES
SECONDARY PREVENTION
Echocardiography in those following a STEMI to reevaluate ventricular function when results are used
to guide therapy*.
I
IIa
B
IIb
III
Echocardiography or radionuclide angiography in
those following a NSTE-ACS when results are used
to guide therapy*.
NSTE-ACS=Non-ST-segment elevation acute coronary syndrome, STEMI=STsegment elevation myocardial infarction
*Includes use of an aldosterone antagonist, digitalis, and/or an implantable
cardioverter defibrillator
RELATIONSHIP BETWEEN EF* AND MORTALITY
Cardiac Mortality %
50
<30
40
30
31-35
20
36-45
10
46-53
0
20
30
40
50
54-60
60
Ejection Fraction (%)
EF=Ejection fraction
*Post myocardial infarction
Brodie B et al. Am J Cardiol 1992;69:1113
>60
70
80
ALDOSTERONE ANTAGONIST: SECONDARY PREVENTION
EPLERENONE POCT-ACUTE MYOCARDIAL INFARCTION HEART
FAILURE EFFICACY AND SURVIVAL STUDY (EPHESUS)
All Cause Mortality (%)
3,313 patients with evidence of heart failure and LVSD (EF <0.40) after a MI
randomized to eplerenone (50 mg) or placebo for 16 months
Eplerenone
Placebo
25
20
15
10
5
0
RR = 0.85, P=0.008
0
6
12
18
24
30
36
Month
Aldosterone inhibition provides significant benefit in patients with
post-MI heart failure and LVSD
EF=Ejection fraction, LVSD=Left ventricular systolic dysfunction,
MI=Myocardial infarction
Pitt B et al. NEJM 2003;348:1309-21
ICD ALGORITHM
AT LEAST ONE MONTH FOLLOWING A MYOCARDIAL INFARCTION
EF < 30%
EF > 40%
EF 31-40%
Additional Marker of
Electrical Instability?
Yes
+
No
EPS
EF=Ejection fraction, EPS=Electrophysiology study, ICD=Implantable
cardioverter defibrillator, Rx=Treatment, SCD=Sudden cardiac death,
NEJM 349:1836,2003
–
No ICD.
Medical Rx
% Mortality Reduction w/ ICD Rx
ICD: SECONDARY PREVENTION*
Overall death
75%
73%
61%
55%
54%
31%
1
27 Months
EF <35%
*Primary prevention of sudden cardiac death
1
Moss AJ. N Engl J Med. 1996;335:1933-1940
Buxton AE. N Engl J Med. 1999;341:1882-1890
3 Moss AF. N Engl J Med. 2002;346:877-883
2
Arrhythmic death
2
39 Months
EF <40%
3
20 Months
EF <30%
PREVENTION
PYRAMID
Secondary
Primary
Primordial
ASA
ACE-I
Rehab
β-blockers
+Primary
Lipids
Hypertension
Smoking cessation
Diabetes
+Primordial
Physical activity
Healthy eating
Ideal weight
Psychosocial factors
Familial predisposition
ACE-1 = angiotensin converting enzyme inhibitor; ASA = aspirin