The ABC’s of the AHA/ACC
Prevention Guidelines
Alessandra Calvo-Friedman, Andrew
DeFilippis, MD, Ty Gluckman MD,
Dominique Ashen, CRNP, PhD, Roger
Blumenthal, MD,
Johns Hopkins Ciccarone
Preventive Cardiology Center
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
Primary Prevention
I IIa IIb III
Aspirin (75-162 mg daily) in intermediate risk
men with a 10 year risk of CHD >10%.
I IIa IIb III
Aspirin (75-162 mg daily) in intermediate risk
women > 65 yrs with a 10 yr risk of CHD >10%
I IIa IIb III
Aspirin in low risk women with a 10 year risk of
CHD <10%.
CHD=Coronary heart disease
Aspirin Recommendations (Continued)
I IIa IIb III
I IIa IIb III
Secondary Prevention
Aspirin (75-325 mg daily) in those with known
CHD or carotid artery or leg artery narrowings
due to plaque.
Aspirin (100-325 mg daily) in those that have
undergone CABG surgery*.
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.
Aspirin Evidence: Primary Prevention in Men
Physicians’ Health Study (PHS)
22,071 men randomized to aspirin (325mg every other day) followed for an
average of 5 years
End point
Myocardial infarction
Fatal
Nonfatal
Total
Relative Risk (95% CI)
P value
0.34 (0.15-0.75)
0.59 (0.47-0.74)
0.56 (0.45-0.70)
0.007
<0.00001
<0.00001
1.51 (0.54-4.28)
1.20 (0.91-1.59)
1.22 (0.93-1.60)
0.43
0.20
0.15
Stroke
Fatal
Nonfatal
Total
Aspirin significantly reduces the risk of MI in men
CI=Confidence interval, MI=Myocardial infarction
Physicians’ Health Study Research Group. NEJM
1989;321:129-35
Aspirin Evidence: Primary Prevention in Women
Womens’ Health Study (WHS)
39,876 women randomized to aspirin (100 mg every other day) or
placebo for an average of 10 years
Aspirin
0.02
Cumulative
Incidence of MI
Placebo
0.01
P=0.83
0.00
0
2
4
6
8
10
Years
Aspirin doesn’t reduce the risk of MI in women
MI=Myocardial infarction
Ridker P et al. NEJM 2005; 352:1293-204
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
0.14
Aspirin + Clopidogrel
Aspirin + Placebo
0.12
0.10
0.08
0.06
0.04
0.02
P<0.001
0.00
0
3
6
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
9
12
ACE Inhibitor Recommendations
I IIa IIb III
I IIa IIb III
Secondary Prevention
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
1500
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
Digitalis: Recommendations
Secondary Prevention
I IIa IIb III
Digitalis in those with symptomatic HF and
LVSD (EF <45%) to reduce hospitalizations for
HF*.
I IIa IIb III
Digitalis in those with asymptomatic LVSD and
normal sinus rhythm.
EF=Ejection fraction, HF=Heart failure, LVSD=Left
ventricular systolic function
*Contraindications include significant sinus or
atrioventricular block unless a permanent pacemaker is
present.
ACE Inhibitor Evidence: Secondary Prevention
Prevention of Events with Angiotensin Converting Enzyme
Inhibition (PEACE) Trial
8,290 patients with stable coronary artery disease and normal left ventricular
function randomized to trandolapril (4 mg) or placebo for 5 years
Primary End Point (%)*
30
Placebo
Trandolapril
25
20
15
10
5
0
0
1
2
3
4
5
6
Years After Randomization
ACE-I do not reduce CV events in low-risk individuals
*Includes death from cardiovascular causes,
myocardial infarction, or coronary revascularization
PEACE Trial Investigators. NEJM 2004;351:2058-2068
ACE Inhibitor Evidence: Secondary Prevention
Comparison between the HOPE and PEACE trials
20
HOPE, placebo
MI, Cardiac death,
or Stroke (%)
HOPE, active drug (ramipril)
PEACE, placebo
15
10
5
0
0
1
2
3
4
5
Years
Patients enrolled in the PEACE trial were at lower risk*
*Reflects greater blood pressure control, revacularization, and use of other risk-reducing medications (i.e.,
antiplatelet therapy, b-blocker, lipid-lowering medication)
CHD=Coronary heart disease, MI=Myocardial infarction
Braunwald, E. et al., NEJM 2004;351:2058-68.
ACE Inhibitor Evidence: Secondary Prevention
AIRE
SAVE
Probability of Event
Radionuclide
EF  40%
0.4
TRACE
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
JNC VII Guidelines for Measurement of BP
Method
Brief Description
In-office
Two readings, 5 minutes apart, sitting in chair.
Confirm elevated reading in contralateral arm.
Ambulatory BP monitoring
Indicated for evaluation of “white-coat” HTN.
Absence of 10–20% BP decrease during sleep
may indicate increased CVD risk.
Self-measurement
Provides information on response to therapy.
May help improve adherence to therapy and
evaluate “white-coat” HTN.
BP=Blood pressure, CVD=Cardiovascular disease,
HTN=Hypertension
Chobanian AV et al. JAMA. 2003;289:2560-2572
Blood Pressure: Risk Increases with Age
National Health and Nutrition Examination Survey (NHANES) III
Percent hypertensive
80
66%
60
51%
38%
40
18%
20
3%
0
72%
9%
18-29 30-39 40-49 50-59 60-69 70-79
Age
Hypertension defined as blood pressure >140/90
mmHg or treatment
JNC-VI. Arch Intern Med. 1997;157:2413-2446
80+
Blood Pressure: Lower is Better
Age at Risk (Y)
80-89
256
128
70-79
64
60-69
32
50-59
16
40-49
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
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
8
4
2
1
0
70 80 90 100 110
Usual Diastolic BP (mm Hg)
JNC VII Causes of Secondary Hypertension
Medical Conditions
Drugs
Chronic kidney disease
NSAIDS
Primary hyperaldosteronism
Oral contraceptives
Renovascular disease
Adrenal steroids
Chronic steroid therapy
Sympathomimetics
Cushing’s syndrome
Cyclosporine or tacrolimus
Pheochromocytoma
Erythropoietin
Aortic coarctation
Ephedra, mu huang, bitter orange
Thyroid or parathyroid disease
Cocaine or amphetamines
Sleep apnea
Alcohol
NSAIDS=Non-steroidal anti-inflammatory drugs
Chobanian AV et al. JAMA. 2003;289:2560-2572
JNC VII Lifestyle Modifications for BP Control
Modification
Recommendation
Approximate SBP
Reduction Range
Weight reduction
Maintain normal body weight
(BMI=18.5-24.9)
5-20 mmHg/10 kg
weight lost
Diet rich in fruits, vegetables, low fat
dairy and reduced in fat
8-14 mmHg
Restrict sodium
intake
<2.4 grams of sodium per day
2-8 mmHg
Physical activity
Regular aerobic exercise for at least
30 minutes on most days of the week
4-9 mmHg
<2 drinks/day for men and <1
drink/day for women
2-4 mmHg
Adopt DASH
eating plan
Moderate alcohol
consumption
BMI=Body mass index, SBP=Systolic blood pressure
Chobanian AV et al. JAMA. 2003;289:2560-2572
JNC VII Guidelines for Management and Treatment
Initial drug therapy
BP
classification
SBP*
mmHg
DBP*
mmHg
Lifestyle
modification
Without compelling
indication
<120 and <80
Encourage
Prehypertension
120–139 or 80–89
Yes
No antihypertensive drug
indicated.
Stage 1
Hypertension
140–159 or 90–99
Yes
Thiazide-type diuretics for
most. May consider ACEI,
ARB, BB, CCB, or
combination.
Stage 2
Hypertension
>160 or >100
Normal
Yes
Two-drug combination for
most† (usually thiazide-type
diuretic and ACEI or ARB or
BB or CCB).
With compelling
indications
Drug(s) for compelling
indications. ‡
Drug(s) for the
compelling
indications.‡
Other antihypertensive
drugs (diuretics, ACEI,
ARB, BB, CCB) as
needed.
ACEI=Angiotensin converting enzyme inhibitor, ARB=Angiotensin receptor blocker, BB=b-blocker, BP=Blood
pressure, CCB=Calcium channel blocker, DBP=Diastolic blood pressure, SBP=Systolic blood pressure
*Treatment determined by highest blood pressure category.
†Initial combined therapy should be used cautiously in
those
at risk for orthostatic hypotension.
‡Treat patients with chronic kidney disease or diabetes
mellitus to blood pressure goal of <130/80 mmHg.
Chobanian AV et al. JAMA. 2003;289:2560-2572
Blood Pressure Recommendations
Secondary Prevention
I IIa IIb III
I IIa IIb III
Initiation or maintenance of lifestyle
modification in those with a BP >120/80
mmHg.
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: Primary Prevention
Antihypertensive and Lipid-Lowering Treatment to Prevent
Heart Attack Trial (ALLHAT)
33,357 patients with HTN and >1 CHD risk factor randomized to
chlorthalidone, amlodipine, or lisinopril for 5 years
Rate of MI or
fatal CHD
.20
Chlrothalidone
Amlodipine
Lisinopril
.16
.12
RR
(95% CI)
P-value
A/C
0.98
(0.90-1.07)
0.65
L/C
0.99
(0.91-1.08)
0.81
.08
.04
0
0
1
2
3
4
5
Years to CHD Event
6
7
There is similar efficacy among BP lowering agents
BP=Blood pressure, CHD=Coronary heart disease,
HTN=Hypertension, MI=Myocardial infarction
ALLHAT Investigators. JAMA. 2002;288:2981-97
Blood Pressure Evidence: Primary Prevention
Losartan Intervention for Endpoint (LIFE) Reduction in
Hypertension Study
Proportion with CV
death, MI, or stroke (%)
9,193 high-risk hypertensive* patients with LVH randomized to losartan
(100 mg) or atenolol (100 mg) for 5 years
16
Atenolol
Losartan
12
8
4
13% RRR, P=0.021
0
0
6
12
18
24
30
36
42
48
54
60
66
Study Month
An ARB provides greater efficacy in patients with LVH
ARBS=Angiotensin receptor blocker strategy, CV=Cardiovascular,
DBP=Diastolic blood presure, LVH=Left ventricular hypertrophy,
MI=Myocardial infarction, SBP=Systolic blood pressure
*Defined by SBP=160-200 mmHg or DBP=95-115 mmHg
Dahlöf B et al. Lancet. 2002;359:995-1003.
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*
I IIa IIb III
Secondary Prevention
A b-blocker in all patients following a MI.
A beta-blocker in all patients with LVSD.
I IIa 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.
b-blocker Evidence: Secondary Prevention
Summary of Secondary Prevention Trials of b-blocker Therapy
Phase of
Treatment
Total #
Patients
RR (95% CI)
Acute
treatment
28,970
0.87 (0.77-0.98)
Secondary
prevention
24,298
0.77 (0.70-0.84)
Overall
53,268
0.81 (0.75-0.87)
0.5
CI=Confidence interval, RR=Relative risk
1.0
RR of death
b-blocker
Placebo
better
better
Antman E, Braunwald E. Acute Myocardial Infarction.
In: Braunwald E, Zipes DP, Libby P, eds. Heart Disease:
A textbook of Cardiovascular Medicine, 6th ed.,
Philadelphia, PA: W.B. Sanders, 2001, 1168.
2.0
Cholesterol Management Guidelines
Secondary Prevention
I IIa IIb III
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.
I IIa IIb 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
I IIa IIb III
Initiation or intensification of LDL-C lowering
drug therapy in those with a baseline or ontreatment 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
Recommendations
As set forth by the
Adult Treatment
Panel III (ATP III)
National Cholesterol
Education Program
(NCEP)
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.
Cholesterol Management Guidelines (Continued)
Goals
As set forth by the
Adult Treatment
Panel III (ATP III)
National Cholesterol
Education Program
(NCEP)
Recommendations
For primary and secondary prevention, HMG-coA reductase
inhibitors (statins) should be first-line in order to achieve the
LDL-C goal.
For those that remain above the LDL-C goal, statin therapy
should be intensified along with the addition of a second
LDL-C lowering agent if needed.
If the TG level is >150 mg/dl or HDL-C level is <40 mg/dl,
emphasize weight management, physical activity, and
smoking cessation.
If the TG level is 200-499 mg/dl after initiation of LDL-C
lowering therapy, consider adding nicotinic acid or a fibrate.
If the TG level is >500 mg/dl, consider adding nicotinic acid
or a fibrate before LDL-C lowering therapy.
TG=Triglyceride
Expert Panel on Detection, Evaluation, and
Treatment of High Blood Cholesterol in Adults. JAMA
2001;285:2486.
Risk Profile Assessment for LDL-C Lowering
A risk assessment tool* is needed for individuals with >2 RFs
10-year CHD Risk
10
20
0
0-1 RF
2 RFs
CAD or Risk
Equivalent**
CAD=Coronary artery disease, CHD=Coronary heart disease, DM=Diabetes mellitus, RF=Risk factor
*Such as the Framingham Risk Score (FRS)
**Includes DM, non-coronary atherosclerotic vascular
disease, and >20% 10-year CHD risk by the FRS
Expert Panel on Detection, Evaluation, and Treatment of
High Blood Cholesterol in Adults. JAMA 2001;285:2486.
Passed torch: President and Mrs. Clinton exit
McDonald’s after his symbolic passage of leadership.
Framingham Risk Score: Men
Step 1: Age Points
Years
20-34
35-39
40-44
45-49
50-54
55-59
60-64
65-69
70-74
75-79
Points
-9
-4
0
3
6
8
10
11
12
13
Step 4: SBP Points
SBP
(mmHg)
<120
120-129
130-139
140-159
>160
If
untreat
ed
0
0
1
1
2
Step 5: Smoking Status Points
If
treated
0
1
2
2
3
Nonsmoker
Smoker
Age
20-39
0
8
Age
40-49
0
5
Age
50-59
0
3
Age
60-69
0
1
Age
70-79
0
1
Step 6: Sum of Points
Age
Total Cholesterol
HDL-C
Systolic Blood Pressure
Smoking Status
Point Total
Step 2: Total Cholesterol Points
TC
(mg/dl)
<160
160-199
200-239
240-279
>280
Age
20-39
0
4
7
9
11
Age
40-49
0
3
5
6
8
Step 3: HDL-C Points
HDL-C (mg/dl)
>60
50-59
40-49
<40
Points
-1
0
1
2
Age
50-59
0
2
3
4
5
Age
60-69
0
1
1
2
3
Age
70-79
0
0
0
1
1
Step 7: 10-year CHD Risk
Point
Total
<0
0
1
2
3
4
5
10-year
Risk
<1%
1%
1%
1%
1%
1%
2%
Point
Total
6
7
8
9
10
11
12
10-year
Risk
2%
3%
4%
5%
6%
8%
10%
Point
Total
13
14
15
16
>17
10-year
Risk
12%
16%
20%
25%
>30%
Framingham Risk Score: Women
Step 1: Age Points
Years
20-34
35-39
40-44
45-49
50-54
55-59
60-64
65-69
70-74
75-79
Points
-7
-3
0
3
6
8
10
12
14
16
Step 4: SBP Points
SBP
(mmHg)
<120
120-129
130-139
140-159
>160
If
untreat
ed
0
1
2
3
4
Step 5: Smoking Status Points
If
treated
0
3
4
5
6
Nonsmoker
Smoker
Age
20-39
0
9
Age
40-49
0
7
Age
50-59
0
4
Age
60-69
0
2
Age
70-79
0
1
Step 6: Sum of Points
Age
Total Cholesterol
HDL-C
Systolic Blood Pressure
Smoking Status
Point Total
Step 2: Total Cholesterol Points
TC
(mg/dl)
<160
160-199
200-239
240-279
>280
Age
20-39
0
4
8
11
13
Age
40-49
0
3
6
8
10
Step 3: HDL-C Points
HDL-C (mg/dl)
>60
50-59
40-49
<40
Points
-1
0
1
2
Age
50-59
0
2
4
5
7
Age
60-69
0
1
2
3
4
Age
70-79
0
1
1
2
2
Step 7: 10-year CHD Risk
Point
Total
<9
9
10
11
12
13
14
10-year
Risk
<1%
1%
1%
1%
1%
2%
2%
Point
Total
15
16
17
18
19
20
21
10-year
Risk
3%
4%
5%
6%
8%
11%
14%
Point
Total
22
23
24
>25
10-year
Risk
17%
22%
27%
>30%
ATP III LDL-C Goals and Cut-points for Drug Therapy
Risk Category
Consider
Drug Therapy
LDL-C Goal
Initiate TLC
High risk:
CHD or CHD risk equivalents
(10-year risk >20%)
<100 mg/dL
(optional goal:
<70 mg/dL)
100 mg/dL
>100 mg/dL
(<100 mg/dL: consider drug
options)
Moderately high risk:
2+ risk factors*
(10-year risk 10% to 20%)
<130 mg/dL
(optional goal:
<100 mg/dL)
130 mg/dL
>130 mg/dL
(100-129 mg/dL: consider
drug options)
Moderate risk:
2+ risk factors*
(10 year risk <10%)
<130 mg/dL
130 mg/dL
>160 mg/dL
Lower risk:
0-1 risk factor*
<160 mg/dL
160 mg/dL
>190 mg/dL
(160-189 mg/dL: LDLlowering drug optional)
*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
Cholesterol absorption inhibitor
Dietary Adjuncts
Cholestyramine (generic and Questran)
Colesevelam (Welchol)
Colestipol (Colestid)
Ezetimibe (Zetia)
Soluble fiber
Soy protein
Stanol esters
HMG-CoA Reductase Inhibitor: Dose-Dependent Effect
The Rule of 6’s
Lovastatin 20/80
28
Pravastatin 20/40
27
Simvastatin 20/80
12
6
35
Fluvastatin 20/80
19
12
12
Atorvastatin 10/80
37
0
10
20
18
30
40
50
60
Reduction of LDL Cholesterol (%)
Each doubling of the statin dose produces an additional 6%
reduction in the LDL-C level
Illingworth DR. Med Clin North Am. 2000;84:2342.
HMG-CoA Reductase Inhibitor: Primary Prevention
West of Scotland Coronary Prevention Study (WOSCOPS)
6,595 men with moderate hypercholesterolemia randomized to pravastatin
(40 mg) or placebo for 5 years
Rate of MI or CHD
death (%)
31% RRR
9
7.5
6
5.3
3
P<0.001
0
Placebo
Pravastatin
Statins provide significant benefit in those with average
cholesterol levels
CHD=Coronary heart disease, MI=Myocardial infarction,
RRR=Relative risk reduction
Shepherd J et al. NEJM 1995;333:1301-1307
HMG-CoA Reductase Inhibitor: Primary Prevention
Air Force/Texas Coronary Atherosclerosis Prevention Study
(AFCAPS/TexCAPS)
6,605 patients with average LDL-C levels randomized to lovastatin (20-40
mg) or placebo for 5.2 years
Rate of MI, unstable
angina, or SCD (%)
37% RRR
6
5.5
4
3.5
2
P<0.001
0
Placebo
Lovastatin
Statins provide significant benefit in those with average
LDL-C levels
MI=Myocardial infarction, RRR=Relative risk reduction,
SCD=Sudden cardiac death
Downs JR et al. JAMA 1998;279(20):1615–1622
HMG-CoA Reductase Inhibitor: Primary Prevention
Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering
Arm (ASCOT-LLA)
Cumulative incidence of
MI and fatal CHD (%)
10,305 patients with hypertension randomized to atorvastatin (10 mg) or
placebo for 5 years
4
3
Atorvastatin 90 mg/dl*
Placebo
126 mg/dl*
36% RRR
2
1
P=0.0005
0
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
Follow-up (yr)
Statins provide significant benefit in moderate- to high-risk
individuals by lowering LDL-C levels below current goals
CHD=Coronary heart disease, RR=Relative risk
*Post-treatment LDL-C level
Sever PS et al. Lancet. 2003;361:1149-1158
HMG-CoA Reductase Inhibitor: Secondary Prevention
Myocardial Ischemia Reduction with Aggressive Cholesterol
Lowering Trial (MIRACL)
Combined cardiovascular
event rate (%)*
4,162 patients with an ACS randomized to atorvastatin (80 mg) or
pravastatin (40 mg) for 24 months
17.4%
Atorvastatin
Placebo
15
14.8%
10
5
RR=0.84, P=0.048
0
0
4
8
12
16
Weeks
Acute intensive therapy significantly reduces the event rate
*Includes death, myocardial infarction, resuscitated
cardiac arrest, recurrent symptomatic myocardial
ischemia requiring emergency rehospitalization.
Schwartz GG et al. JAMA 2001;285:1711-1718
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
Cholesterol and Recurrent Events (CARE) Study
4,159 patients with a history of MI randomized to pravastatin (40 mg) or
placebo for 5 years
Rate of MI or CHD
death (%)
24% RRR
15
13.2
10.2
10
5
P=0.003
0
Placebo
Pravastatin
Statins provide significant benefit in those with average
cholesterol levels
CHD=Coronary heart disease, MI=Myocardial infarction,
RRR=Relative risk reduction
Sacks FM et al. NEJM 1996;335:1001–1009
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
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%)
Event Rate Ratio (95% CI)
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
HMG-CoA Reductase Inhibitor: Dose-Dependent Effect
The Rule of 6’s
Lovastatin 20/80
28
Pravastatin 20/40
27
Simvastatin 20/80
12
6
35
Fluvastatin 20/80
19
12
12
Atorvastatin 10/80
37
0
10
20
18
30
40
50
60
Reduction of LDL Cholesterol (%)
Each doubling of the statin dose produces an additional 6%
reduction in the LDL-C level
Illingworth DR. Med Clin North Am. 2000;84:2342.
HMG-CoA Reductase Inhibitor: Primary Prevention
West of Scotland Coronary Prevention Study (WOSCOPS)
6,595 men with moderate hypercholesterolemia randomized to pravastatin
(40 mg) or placebo for 5 years
Rate of MI or CHD
death (%)
31% RRR
9
7.5
6
5.3
3
P<0.001
0
Placebo
Pravastatin
Statins provide significant benefit in those with average
cholesterol levels
CHD=Coronary heart disease, MI=Myocardial infarction,
RRR=Relative risk reduction
Shepherd J et al. NEJM 1995;333:1301-1307
HMG-CoA Reductase Inhibitor: Primary Prevention
Air Force/Texas Coronary Atherosclerosis Prevention Study
(AFCAPS/TexCAPS)
6,605 patients with average LDL-C levels randomized to lovastatin (20-40
mg) or placebo for 5.2 years
Rate of MI, unstable
angina, or SCD (%)
37% RRR
6
5.5
4
3.5
2
P<0.001
0
Placebo
Lovastatin
Statins provide significant benefit in those with average
LDL-C levels
MI=Myocardial infarction, RRR=Relative risk reduction,
SCD=Sudden cardiac death
Downs JR et al. JAMA 1998;279(20):1615–1622
HMG-CoA Reductase Inhibitor: Primary Prevention
Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering
Arm (ASCOT-LLA)
Cumulative incidence of
MI and fatal CHD (%)
10,305 patients with hypertension randomized to atorvastatin (10 mg) or
placebo for 5 years
4
3
Atorvastatin 90 mg/dl*
Placebo
126 mg/dl*
36% RRR
2
1
P=0.0005
0
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
Follow-up (yr)
Statins provide significant benefit in moderate- to high-risk
individuals by lowering LDL-C levels below current goals
CHD=Coronary heart disease, RR=Relative risk
*Post-treatment LDL-C level
Sever PS et al. Lancet. 2003;361:1149-1158
HMG-CoA Reductase Inhibitor: Secondary Prevention
Myocardial Ischemia Reduction with Aggressive Cholesterol
Lowering Trial (MIRACL)
Combined cardiovascular
event rate (%)*
4,162 patients with an ACS randomized to atorvastatin (80 mg) or
pravastatin (40 mg) for 24 months
17.4%
Atorvastatin
Placebo
15
14.8%
10
5
RR=0.84, P=0.048
0
0
4
8
12
16
Weeks
Acute intensive therapy significantly reduces the event rate
*Includes death, myocardial infarction, resuscitated
cardiac arrest, recurrent symptomatic myocardial
ischemia requiring emergency rehospitalization.
Schwartz GG et al. JAMA 2001;285:1711-1718
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
Cholesterol and Recurrent Events (CARE) Study
4,159 patients with a history of MI randomized to pravastatin (40 mg) or
placebo for 5 years
Rate of MI or CHD
death (%)
24% RRR
15
13.2
10.2
10
5
P=0.003
0
Placebo
Pravastatin
Statins provide significant benefit in those with average
cholesterol levels
CHD=Coronary heart disease, MI=Myocardial infarction,
RRR=Relative risk reduction
Sacks FM et al. NEJM 1996;335:1001–1009
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
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%)
Event Rate Ratio (95% CI)
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
Nicotinic Acid: Efficacy at Raising HDL-C
30%
Change from Baseline
30
22%
20
10
26%
10%
–9%
–14%
–5%
-20
–17%
–11%
–22%
–21%
LDL-C
–28%
-30
–35%
-40
–39%
-50
Dose (mg)
HDL-C
15%
0
-10
30%
500
1000
1500
Goldberg A et al. Am J Cardiol 2000;85:1100-1105
2000
2500
–44%
3000
TG
Fibrate: Primary and Secondary Prevention
% CHD Death/Nonfatal MI
30
42%
Rx
25
22%
Placebo
22.3
21.7***
9%
20
17.3
66%
15
10
5
34%
2.7
4.1***
13.6
15.0
13.0
8.0
2.7
0
HHS
HHS*
PRIMARY PREVENTION
BIP
BIP**
VA-HIT
SECONDARY PREVENTION
*Post hoc analysis of subgroup with TG >200 mg/dL and HDL-C <42 mg/dL.
**Post hoc analysis of subgroup with TG 200 mg/dL and HDL-C <35 mg/dL.
***Difference between placebo and Rx for primary endpoint was statistically significant (p < 0.05).
Frick MH et al. NEJM 1987;317:1237-1245
Manninen V et al. Circulation 1992;85:37-45
BIP Study Group. Circulation 2000;102:21-27
Rubins HB et al. NEJM 1999;341:410-418
Cigarette Smoking Cessation Guidelines
Goals
Complete cessation
No environmental
tobacco smoke exposure
I 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*
Agent
Caution
Side
Effects
Dosage
Duration
Instructions
Bupropion
SR
(Zyban®)
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.
Transdermal
Nicotine
Patch**
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
*Pharmacotherapy combined with behavioral support
provides the best success rate
**Other nicotine replacement therapy options include:
nicotine gum, lozenge, inhaler, nasal spray
Maintenance
(8 weeks,
but may be
used up to 6
months)
4 weeks
2 weeks
2 weeks
8 weeks
Apply to different
hairless site
daily.
Remove before
bed for insomnia.
Start at <15 mg
for <10 cigs/day
Cigarette Smoking Cessation: Primary Prevention
893 smokers randomized to 9 weeks of buproprion (150 mg a day for 3 days
and then 150 mg twice daily), NRT (21 mg patch weeks 2-7, 14 mg patch
week 8, and 7 mg patch week 9), bupropion and NRT, or placebo
Placebo
(n=160)
NRT
(n=244)
Bupropion Nicotine patch and
(n=244) Bupropion (n=245)
Abstinence rate
at 6 months
18.8%
21.3%
34.8%a,b
38.8%a,c,d
Abstinence rate
at 12 months
15.6%
16.4%
30.3%a,c
35.5%a,c,e
Bupropion with or without NRT provides the greatest benefit
NRT=Nicotine replacement therapy
ap<0.001
when compared to placebo
when compared to NRT
cp<0.001 when compared to NRT
dp=0.37 when compared to buproprion
ep=0.22 when compared to buproprion
bp=0.001
Jorenby DE et al. NEJM 1999;340:685-91
S
u
d
y
1
2
p
<
0
0
0
1
Smoking Cessation Pharmacotherapy: Varenicline
Two trials compared treatment with varenicline,
a nicotine acetylcholine receptor agonist, to
treatment with buproprion or placebo.
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.
o
V
B
p
<
0
0
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
I IIa IIb III
Start weight management and
physical activity as appropriate.
Women: <35 inches
Men: <40 inches
I IIa IIb III
10% weight reduction
within the first year of
therapy
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.
If BMI and/or waist circumference is
above goal, initiate caloric restriction,
measures to increase caloric
expenditure, and treatment strategies
for the metabolic syndrome.
Prevalence of Obesity in U.S. Adults
1991
1996
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
Recommendations
Goal HbA1C <7%
Intensive lifestyle modification to prevent the development
of DM (especially in those with the metabolic syndrome)
I IIa IIb III
I IIa IIb III
Aggressive management of CV risk factors (i.e., tobacco
use, hypertension, dyslipidemia, physical inactivity, and
overweight and obese states)
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
Coordination of diabetic care with the patient’s primary
physician and/or endocrinologist.
CV=Cardiovascular, DM=Diabetes mellitus,
HbA1C=Glycosylated hemoglobin
The Metabolic Syndrome
• Consists of a constellation
of major risk factors, lifehabit risk factors, and
emerging risk factors
• Over-represented among
populations with
cardiovascular disease
• Often occurs in individuals
with a distinctive body-type
including an increased
abdominal circumference
ATP III Definition of the Metabolic Syndrome
Defined by presence of >3 risk factors
Risk Factor
Defining Level
Waist circumference (abdominal obesity)
>40 in (>102 cm) in men
>35 in (>88 cm) in women
Triglyceride level
>150 mg/dl
HDL-C level
<40 mg/dl in men
<50 mg/dl in women
Blood pressure
>130/>85 mmHg
Fasting glucose
>100 mg/dl
HDL-C=High-density lipoprotein cholesterol
Expert Panel on Detection, Evaluation, and
Treatment of High Blood Cholesterol in Adults.
JAMA 2001;285:2486-2497
Metabolic Syndrome: Risk of Developing DM
Finnish Diabetes Prevention Study
522 overweight (mean BMI=31 kg/m2) patients with impaired fasting
glucose† randomized to intervention‡ or usual care for 3.2 years
0.25
23%
0.2
Intervention
Control
0.15
0.1
11%
0.05
0
% with Diabetes Mellitus
Lifestyle modification reduces the risk of developing DM
†Defined
as a glucose >140 mg/dl 2 hours after an oral glucose challenge
‡Aimed
at reducing weight (>5%), total intake of fat
(<30% total calories) and saturated fat (<10% total
calories); increasing uptake of fiber (>15 g/1000 cal);
and physical activity (moderate at least 30 min/day)
Tuomilehto J et al. NEJM 2001;344:1343-1350
Metabolic Syndrome: Risk of Developing DM
Diabetes Prevention Program (DPP)
Cumulative incidence (%)
Incidence of DM (%)
3,234 patients with elevated fasting and post-load glucose levels
developing
diabetes
randomized to placebo,Percent
metformin
(850
mg twice daily), or lifestyle
modification*
for 2.8 years
All participants
Lifestyle
(n=1079, p<0.001 vs. Met , p<0.001 vs. Plac )
Placebo
Metformin (n=1073, p<0.001 vs. Plac)
Placebo (n=1082)
40
40
Metformin
Lifestyle modification
30
30
20
20
10
10
00
0
00
1
1
22
Years from randomization
3
3
44
Years
Lifestyle modification reduces the risk of developing DM
*Includes 7% weight loss and at least 150 minutes of
physical activity per week
Knowler WC et al. NEJM 2002;346:393-403
Exercise Guidelines
Goals
Minimum: 30 minutes,
5 days per week
Optimal: 30 minutes daily
I IIa IIb III
Recommendations
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
I IIa IIb III
Echocardiography in those following a
STEMI to re-evaluate ventricular function
when results are used to guide therapy*.
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=ST-segment elevation
myocardial infarction
*Includes use of an aldosterone antagonist, digitalis,
and/or an implantable cardioverter defibrillator
Digitalis: Recommendations
Secondary Prevention
I IIa IIb III
Digitalis in those with symptomatic HF and
LVSD (EF <45%) to reduce hospitalizations for
HF*.
I IIa IIb III
Digitalis in those with asymptomatic LVSD and
normal sinus rhythm.
EF=Ejection fraction, HF=Heart failure, LVSD=Left
ventricular systolic function
*Contraindications include significant sinus or
atrioventricular block unless a permanent pacemaker is
present.
Relationship Between EF* and Mortality
Cardiac Mortality %
50
<30
40
30
31-35
20
36-45
10
46-53
0
20
30
EF=Ejection fraction
*Post myocardial infarction
Brodie B et al. Am J Cardiol 1992;69:1113
54-60
>60
40
50
60
70
Ejection Fraction (%)
80
Aldosterone Antagonist: Secondary Prevention
Randomized Aldactone Evaluation Study (RALES)
1,663 patients with NYHA Class III or IV HF and LVSD (EF <0.35)
randomized to spironolactone (25 mg) or placebo (50 mg) for 24 months
Survival (%)
1.00
Spironolactone
Placebo
.90
.80
.70
.60
.50
RR = 0.70, P<0.001
0
0
3
6
9
12 15 18 21 24 27 30 33
36
Months
Aldosterone inhibition provides significant benefit in
patients with advanced heart failure
EF=Ejection fraction, HF=Heart failure, LVSD=Left
ventricular systolic dysfunction, NYHA=New York Heart
Association
Pitt B et al. NEJM 1999;341:709-717
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
+
EPS
EF=Ejection fraction, EPS=Electrophysiology study,
ICD=Implantable cardioverter defibrillator,
Rx=Treatment, SCD=Sudden cardiac death,
NEJM 349:1836,2003
No
-
No ICD.
Medical Rx
% Mortality Reduction w/ ICD Rx
ICD: Secondary Prevention*
Overall death
80
60
61%
40
31%
20
0
1
*Primary prevention of sudden cardiac death
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
55%
54%
MADIT
27 Months
EF <35%
1
73%
75%
2
MUSTT
39 Months
EF <40%
3
MADIT-II
20 Months
EF <30%
Prevention Pyramid
Secondary
Primary
ASA
ACE-I
Rehab
β-blockers
+Primary
Lipids
Hypertension
Smoking cessation
Diabetes
+Primordial
Primordial
Physical activity
Healthy eating
Ideal weight
Psychosocial factors
Familial predisposition
ACE-1 = angiotensin converting enzyme inhibitor; ASA = aspirin