EXERCISE/WEIGHT/DIET- HOW MUCH/HOW LITTLE ?

1
The ABCs 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
2
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.
CHDCoronary heart disease
Celermajer DS. JACC 2005451994-6
3
Aspirin Recommendations
Primary Prevention
Aspirin (75-162 mg daily) in intermediate risk
men with a 10 year risk of CHD gt10. Aspirin
(75-162 mg daily) in intermediate risk women gt 65
yrs with a 10 yr risk of CHD gt10 Aspirin in
low risk women with a 10 year risk of CHD lt10.
CHDCoronary heart disease
4
Aspirin Recommendations (Continued)
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.
CABGCoronary artery bypass graft, CHDCoronary
heart disease
To be administered within the first 48 hours
after surgery in order to reduce the risk of
saphenous vein graft failure. Doses gt162 mg/day
may be continued for up to one year.
5
Physicians Health Study (PHS)
Aspirin Evidence Primary Prevention in Men
22,071 men randomized to aspirin (325mg every
other day) followed for an average of 5
years Aspirin significantly reduces the
risk of MI in men
CIConfidence interval, MIMyocardial infarction
Physicians Health Study Research Group. NEJM
1989321129-35
6
Womens Health Study (WHS)
Aspirin Evidence Primary Prevention in Women
39,876 women randomized to aspirin (100 mg every
other day) or placebo for an average of 10
years Aspirin doesnt reduce the risk
of MI in women
Aspirin
Placebo
Cumulative Incidence of MI
P0.83
Years
MIMyocardial infarction
Ridker P et al. NEJM 2005 3521293-204
7
Clopidogrel Evidence Secondary Prevention
Clopidogrel in Unstable Angina to Prevent
Recurrent Events (CURE) Trial
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
Rate of death, myocardial infarction, or stroke
Plt0.001
3
6
9
0
12
Months of Follow Up
DAPDual antiplatelet therapy, NSTE-ACSNon
ST-segment elevation acute coronary syndrome
The CURE Trial Investigators. NEJM.
2001345494-502
8
ACE Inhibitor Recommendations
Secondary Prevention
An ACE inhibitor in those following a MI,
regardless of EF or in those with CAD along with
hypertension (SBP gt120 mmHg), LVSD (EF lt0.40),
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.
ACEAngiotensin converting enzyme, CADCoronary
artery disease, CKDChronic kidney disease,
CVCardiovascular, DMDiabetes mellitus,
EFEjection fraction, LVSDLeft ventricular
systolic dysfunction, MIMyocardial infarction,
SBPSystolic blood pressure
Defined by previous MI or angiographically
significant CAD.
9
ACE Inhibitor Evidence Secondary Prevention
Heart Outcomes Prevention and Evaluation (HOPE)
Study
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 ACE-I reduce CV
events in high-risk individuals
0.20
Ramipril
0.15
Placebo
CV death, MI, or stroke ()
0.10
0.05
22 RRR, Plt0.001
0.00
0
500
1000
1500
Days of Follow-Up
ACE-IAngiotensin converting enzyme inhibitors,
DMDiabetes mellitus, CVCardiovascular, HFHeart
failure, LVSDLeft ventricular systolic
dysfunction, MIMyocardial infarction
HOPE Investigators. NEJM 2000342145-153
10
Digitalis Recommendations
Secondary Prevention
Digitalis in those with symptomatic HF and LVSD
(EF lt45) to reduce hospitalizations for
HF. Digitalis in those with asymptomatic LVSD
and normal sinus rhythm.
EFEjection fraction, HFHeart failure, LVSDLeft
ventricular systolic function
Contraindications include significant sinus or
atrioventricular block unless a permanent
pacemaker is present.
11
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 ACE-I do not reduce CV events
in low-risk individuals
30 25 20 15 10 5 0
Placebo Trandolapril
Primary End Point ()
0 1 2 3 4 5
6
Years After Randomization
Includes death from cardiovascular causes,
myocardial infarction, or coronary
revascularization
PEACE Trial Investigators. NEJM 20043512058-2068
12
ACE Inhibitor Evidence Secondary Prevention
Comparison between the HOPE and PEACE trials
MI, Cardiac death, or Stroke ()
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)
CHDCoronary heart disease, MIMyocardial
infarction
Braunwald, E. et al., NEJM 20043512058-68.
13
ACE Inhibitor Evidence Secondary Prevention
AIREClinical and/or radiographic signs of HF
SAVERadionuclideEF 40
TRACEEchocardiogramEF 35
Probability of Event
0.1
OR 0.74 (0.660.83)
Years
ACE-I provide substantial benefit in post-MI LVSD
ACE-IAngiotensin converting enzyme inhibitors,
LVSDLeft ventricular systolic dysfunction,
MIMyocardial infarction, OROdds ratio
Flather MD, et al. Lancet. 200035515751581
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16
JNC VII Guidelines for Measurement of BP
BPBlood pressure, CVDCardiovascular disease,
HTNHypertension
Chobanian AV et al. JAMA. 20032892560-2572
17
Blood Pressure Risk Increases with Age
National Health and Nutrition Examination Survey
(NHANES) III
72
66
51
38
Percent hypertensive
18
9
3
18-29
30-39
40-49
60-69
70-79
80
50-59
Age
Hypertension defined as blood pressure gt140/90
mmHg or treatment
JNC-VI. Arch Intern Med. 19971572413-2446
18
Blood Pressure Lower is Better
Ischemic Heart Disease Mortality
Age at Risk (Y)
Age at Risk (Y)
80-89
80-89
70-79
70-79
60-69
60-69
50-59
50-59
Ischemic Heart Disease Mortality
Ischemic Heart Disease Mortality
40-49
40-49
Usual Diastolic BP (mm Hg)
Usual Systolic BP (mm Hg)
BPBlood pressure
Prospective Studies Collaboration. Lancet.
20023601903-1913
19
JNC VII Causes of Secondary Hypertension
Medical Conditions
Chronic kidney disease
Primary hyperaldosteronism
Renovascular disease
Chronic steroid therapy
Cushings syndrome
Pheochromocytoma
Aortic coarctation
Thyroid or parathyroid disease
Sleep apnea
Drugs
NSAIDS
Oral contraceptives
Adrenal steroids
Sympathomimetics
Cyclosporine or tacrolimus
Erythropoietin
Ephedra, mu huang, bitter orange
Cocaine or amphetamines
Alcohol
NSAIDSNon-steroidal anti-inflammatory drugs
Chobanian AV et al. JAMA. 20032892560-2572
20
JNC VII Lifestyle Modifications for BP Control
Modification Recommendation Approximate SBP Reduction Range
Weight reduction Maintain normal body weight (BMI18.5-24.9) 5-20 mmHg/10 kg weight lost
Adopt DASH eating plan Diet rich in fruits, vegetables, low fat dairy and reduced in fat 8-14 mmHg
Restrict sodium intake lt2.4 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
Moderate alcohol consumption lt2 drinks/day for men and lt1 drink/day for women 2-4 mmHg
BMIBody mass index, SBPSystolic blood pressure
Chobanian AV et al. JAMA. 20032892560-2572
21
JNC VII Guidelines for Management and Treatment
and
or
or
or
ACEIAngiotensin converting enzyme inhibitor,
ARBAngiotensin receptor blocker, BBb-blocker,
BPBlood pressure, CCBCalcium channel blocker,
DBPDiastolic blood pressure, SBPSystolic 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 lt130/80 mmHg.
Chobanian AV et al. JAMA. 20032892560-2572
22
Blood Pressure Recommendations
Secondary Prevention
Initiation or maintenance of lifestyle
modification in those with a BP gt120/80 mmHg.
Use of an ACE inhibitor and/or b-blocker in
those with a BP gt140/90 mmHg. Other drugs
(i.e., thiazide diuretics) should be added in
order to achieve the desired BP.
ACEAngiotensin converting enzyme, BPBlood
pressure, CKDChronic kidney disease, DMDiabetes
mellitus
A BP gt130/80 mmHg should be used for individuals
with CKD or DM
23
Blood Pressure Evidence Primary Prevention
Antihypertensive and Lipid-Lowering Treatment to
Prevent Heart Attack Trial (ALLHAT)
33,357 patients with HTN and gt1 CHD risk factor
randomized to chlorthalidone, amlodipine, or
lisinopril for 5 years There is similar
efficacy among BP lowering agents
Chlrothalidone Amlodipine Lisinopril
Rate of MI or fatal CHD
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
Years to CHD Event
BPBlood pressure, CHDCoronary heart disease,
HTNHypertension, MIMyocardial infarction
ALLHAT Investigators. JAMA. 20022882981-97
24
Blood Pressure Evidence Primary Prevention
Losartan Intervention for Endpoint (LIFE)
Reduction in Hypertension Study
9,193 high-risk hypertensive patients with LVH
randomized to losartan (100 mg) or atenolol (100
mg) for 5 years An ARB provides greater
efficacy in patients with LVH
16
Atenolol Losartan
12
Proportion with CV death, MI, or stroke ()
8
4
13 RRR, P0.021
0
0
6
12
18
24
30
36
42
48
54
60
66
Study Month
ARBSAngiotensin receptor blocker strategy,
CVCardiovascular, DBPDiastolic blood presure,
LVHLeft ventricular hypertrophy, MIMyocardial
infarction, SBPSystolic blood pressure
Defined by SBP160-200 mmHg or DBP95-115 mmHg
Dahlöf B et al. Lancet. 2002359995-1003.
25
Blood Pressure Evidence Secondary Prevention
Comparison of Amlodipine vs Enalapril to Limit
Occurrences of Thrombosis (CAMELOT) Trial
1,991 patients with CAD and a DBP lt100 mmHg
randomized to amloidipine (10 mg), enalapril (20
mg), or placebo for 2 years A BP lt130/80
mmHg is associated with fewer CV events
130/78
0.25
Placebo
Follow-up BP (mmHg)
124/77
Enalapril
0.20
125/77
Amlodipine
0.15
CV event rate
0.10
0.05
0
6
12
18
24
0
Months
BPBlood pressure, CADCoronary artery disease,
CVCardiovascular, DBPDiastolic blood pressure,
HFHeart failure, MIMyocardial infarction,
PADPeripheral arterial disease, TIATransient
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 20042922217-26.
26
b-blocker Recommendations
Secondary Prevention
A b-blocker in all patients following a MI. A
beta-blocker in all patients with LVSD. A
b-blocker in those with other forms of CV disease
or DM, unless contraindicated.
CVCardiovascular, DMDiabetes mellitus,
LVSDLeft ventricular systolic dysfunction,
MIMyocardial infarction
Relative contraindications include asthma,
chronic obstructive pulmonary disease, insulin
dependent diabetes mellitus, severe peripheral
arterial disease, and a PR interval gt0.24 seconds.
27
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
1.0
2.0
RR of death
b-blocker better
Placebo better
CIConfidence interval, RRRelative risk
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.
28
Cholesterol Management Guidelines
Secondary Prevention
Restriction of saturated fat (lt7 of total
calories) and cholesterol (lt200 mg/day) in all
patients. Promotion of daily physical activity
and weight management in all patients.
Increase in w-3 fatty acid consumption in all
patients.
LDL-CLow density lipoprotein cholesterol
29
Cholesterol Management Guidelines (Continued)
Secondary Prevention
Initiation or intensification of LDL-C lowering
drug therapy in those with a baseline or
on-treatment LDL-C level gt100 mg/dl. Initiation
of LDL-C lowering drug therapy in those with a
baseline LDL-C level lt100 mg/dl based on clinical
judgment.
LDL-CLow density lipoprotein cholesterol
30
Cholesterol Management Guidelines (Continued)
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 (lt7 of total
  calories) and cholesterol (lt200 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 20012852486.
31
Cholesterol Management Guidelines (Continued)
As set forth by the Adult Treatment Panel III
(ATP III) National Cholesterol Education Program
(NCEP)
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 gt150 mg/dl
or HDL-C level is lt40 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 gt500 mg/dl, consider adding
nicotinic acid or a fibrate before LDL-C lowering
therapy.
TGTriglyceride
Expert Panel on Detection, Evaluation, and
Treatment of High Blood Cholesterol in Adults.
JAMA 20012852486.
32
Risk Profile Assessment for LDL-C Lowering
A risk assessment tool is needed for individuals
with gt2 RFs
10-year CHD Risk
CAD or Risk Equivalent
CADCoronary artery disease, CHDCoronary heart
disease, DMDiabetes mellitus, RFRisk factor
Such as the Framingham Risk Score (FRS)
Includes DM, non-coronary atherosclerotic
vascular disease, and gt20 10-year CHD risk by
the FRS
Expert Panel on Detection, Evaluation, and
Treatment of High Blood Cholesterol in Adults.
JAMA 20012852486.
33
Passed torch President and Mrs. Clinton exit
McDonalds after his symbolic passage of
leadership.
34
Framingham Risk Score Men
Step 1 Age Points
Step 4 SBP Points
Step 5 Smoking Status Points
Years Points
20-34 -9
35-39 -4
40-44 0
45-49 3
50-54 6
55-59 8
60-64 10
65-69 11
70-74 12
75-79 13
SBP (mmHg) If untreated If treated
lt120 0 0
120-129 0 1
130-139 1 2
140-159 1 2
gt160 2 3
Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79
Nonsmoker 0 0 0 0 0
Smoker 8 5 3 1 1
Step 6 Sum of Points
Age
Total Cholesterol
HDL-C
Systolic Blood Pressure
Smoking Status
Point Total
Step 2 Total Cholesterol Points
Step 7 10-year CHD Risk
TC (mg/dl) Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79
lt160 0 0 0 0 0
160-199 4 3 2 1 0
200-239 7 5 3 1 0
240-279 9 6 4 2 1
gt280 11 8 5 3 1
Point Total 10-year Risk Point Total 10-year Risk Point Total 10-year Risk
lt0 lt1 6 2 13 12
0 1 7 3 14 16
1 1 8 4 15 20
2 1 9 5 16 25
3 1 10 6 gt17 gt30
4 1 11 8
5 2 12 10
Step 3 HDL-C Points
HDL-C (mg/dl) Points
gt60 -1
50-59 0
40-49 1
lt40 2
35
Framingham Risk Score Women
Step 1 Age Points
Step 4 SBP Points
Step 5 Smoking Status Points
Years Points
20-34 -7
35-39 -3
40-44 0
45-49 3
50-54 6
55-59 8
60-64 10
65-69 12
70-74 14
75-79 16
SBP (mmHg) If untreated If treated
lt120 0 0
120-129 1 3
130-139 2 4
140-159 3 5
gt160 4 6
Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79
Nonsmoker 0 0 0 0 0
Smoker 9 7 4 2 1
Step 6 Sum of Points
Age
Total Cholesterol
HDL-C
Systolic Blood Pressure
Smoking Status
Point Total
Step 2 Total Cholesterol Points
Step 7 10-year CHD Risk
TC (mg/dl) Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79
lt160 0 0 0 0 0
160-199 4 3 2 1 1
200-239 8 6 4 2 1
240-279 11 8 5 3 2
gt280 13 10 7 4 2
Point Total 10-year Risk Point Total 10-year Risk Point Total 10-year Risk
lt9 lt1 15 3 22 17
9 1 16 4 23 22
10 1 17 5 24 27
11 1 18 6 gt25 gt30
12 1 19 8
13 2 20 11
14 2 21 14
Step 3 HDL-C Points
HDL-C (mg/dl) Points
gt60 -1
50-59 0
40-49 1
lt40 2
36
ATP III LDL-C Goals and Cut-points for Drug
Therapy
Risk Category LDL-C Goal Initiate TLC Consider Drug Therapy
High risk CHD or CHD risk equivalents (10-year risk gt20) lt100 mg/dL (optional goal lt70 mg/dL) ?100 mg/dL gt100 mg/dL (lt100 mg/dL consider drug options)
Moderately high risk 2 risk factors (10-year risk 10 to 20) lt130 mg/dL (optional goal lt100 mg/dL) ?130 mg/dL gt130 mg/dL (100-129 mg/dL consider drug options)
Moderate risk 2 risk factors (10 year risk lt10) lt130 mg/dL ?130 mg/dL gt160 mg/dL
Lower risk 0-1 risk factor lt160 mg/dL ?160 mg/dL gt190 mg/dL (160-189 mg/dL LDL-lowering drug optional)
Risk factors for cardiovascular disease include
cigarettes smoking, hypertension (blood pressure
gt140/90 mmHg or on antihypertensive medication,
HDL-C lt40 mg/dl (gt60 mg/dl is a negative risk
factor), family history of premature CHD, age gt45
years in men or gt55 years in women.
ATPAdult Treatment Panel, CHDCoronary heart
disease, LDL-CLow-density lipoprotein
cholesterol, TLCTherapeutic lifestyle changes
Grundy, S. et al. Circulation 2004110227-39.
37
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
38
HMG-CoA Reductase Inhibitor Dose-Dependent Effect
The Rule of 6s
Each doubling of the statin dose produces an
additional 6 reduction in the LDL-C level
Illingworth DR. Med Clin North Am. 20008423-42.
39
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 Statins provide significant
benefit in those with average cholesterol levels
31 RRR
9
7.5
6
5.3
Rate of MI or CHD death ()
3
Plt0.001
0
Placebo
Pravastatin
CHDCoronary heart disease, MIMyocardial
infarction, RRRRelative risk reduction
Shepherd J et al. NEJM 19953331301-1307
40
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 Statins provide
significant benefit in those with average LDL-C
levels
37 RRR
5.5
6
4
3.5
Rate of MI, unstable angina, or SCD ()
2
Plt0.001
0
Placebo
Lovastatin
MIMyocardial infarction, RRRRelative risk
reduction, SCDSudden cardiac death
Downs JR et al. JAMA 1998279(20)16151622
41
HMG-CoA Reductase Inhibitor Primary Prevention
Anglo-Scandinavian Cardiac Outcomes TrialLipid
Lowering Arm (ASCOT-LLA)
10,305 patients with hypertension randomized to
atorvastatin (10 mg) or placebo for 5
years Statins provide significant
benefit in moderate- to high-risk individuals by
lowering LDL-C levels below current goals
4
Atorvastatin 90 mg/dl Placebo 126
mg/dl
3
36 RRR
2
Cumulative incidence of MI and fatal CHD ()
1
P0.0005
0
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
Follow-up (yr)
CHDCoronary heart disease, RRRelative risk
Post-treatment LDL-C level
Sever PS et al. Lancet. 20033611149-1158
42
HMG-CoA Reductase Inhibitor Secondary Prevention
Myocardial Ischemia Reduction with Aggressive
Cholesterol Lowering Trial (MIRACL)
4,162 patients with an ACS randomized to
atorvastatin (80 mg) or pravastatin (40 mg) for
24 months Acute intensive therapy
significantly reduces the event rate
17.4
Atorvastatin Placebo
14.8
Combined cardiovascular event rate ()
RR0.84, P0.048
4
8
12
16
0
Weeks
Includes death, myocardial infarction,
resuscitated cardiac arrest, recurrent
symptomatic myocardial ischemia requiring
emergency rehospitalization.
Schwartz GG et al. JAMA 20012851711-1718
43
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 Acute intensive therapy
significantly reduces the event rate
30
Atorvastatin Pravastatin
16 RRR
25
20
Recurrent MI or Cardiac Death
15
10
5
P 0.005
0
3 6 9 12 15 18 21 24 27
30
Follow-up (months)
ACSAcute coronary syndrome, CVCardiovascular,
MIMyocardial infarction, RRRRelative risk
reduction
Cannon CP et al. NEJM 20043501495-1504
44
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 Statins provide
significant benefit in those with average LDL-C
levels
30 RRR
11.5
12
8.2
8
Mortality ()
4
Plt0.001
0
Placebo
Simvastatin
MIMyocardial infarction, RRRRelative risk
reduction
4S Group. Lancet 199434413831389
45
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 Statins provide significant
benefit in those with average cholesterol levels
24 RRR
15
13.2
10.2
10
Rate of MI or CHD death ()
5
P0.003
0
Placebo
Pravastatin
CHDCoronary heart disease, MIMyocardial
infarction, RRRRelative risk reduction
Sacks FM et al. NEJM 199633510011009
46
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 Statins provide significant
benefit across a broad range of LDL-C levels
Event Rate Ratio (95 CI)
Baseline LDL-C (mg/dL) Statin (n 10,269) Placebo (n 10,267)
lt100 282 (16.4) 358 (21.0)
100129 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 (0.720.81) Plt0.0001
CADCoronary artery disease, CIConfidence
interval, DMDiabetes mellitus,
HPS Collaborative Group. Lancet 20023607-22
47
HMG-CoA Reductase Inhibitor Dose-Dependent Effect
The Rule of 6s
Each doubling of the statin dose produces an
additional 6 reduction in the LDL-C level
Illingworth DR. Med Clin North Am. 20008423-42.
48
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 Statins provide significant
benefit in those with average cholesterol levels
31 RRR
9
7.5
6
5.3
Rate of MI or CHD death ()
3
Plt0.001
0
Placebo
Pravastatin
CHDCoronary heart disease, MIMyocardial
infarction, RRRRelative risk reduction
Shepherd J et al. NEJM 19953331301-1307
49
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 Statins provide
significant benefit in those with average LDL-C
levels
37 RRR
5.5
6
4
3.5
Rate of MI, unstable angina, or SCD ()
2
Plt0.001
0
Placebo
Lovastatin
MIMyocardial infarction, RRRRelative risk
reduction, SCDSudden cardiac death
Downs JR et al. JAMA 1998279(20)16151622
50
HMG-CoA Reductase Inhibitor Primary Prevention
Anglo-Scandinavian Cardiac Outcomes TrialLipid
Lowering Arm (ASCOT-LLA)
10,305 patients with hypertension randomized to
atorvastatin (10 mg) or placebo for 5
years Statins provide significant
benefit in moderate- to high-risk individuals by
lowering LDL-C levels below current goals
4
Atorvastatin 90 mg/dl Placebo 126
mg/dl
3
36 RRR
2
Cumulative incidence of MI and fatal CHD ()
1
P0.0005
0
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
Follow-up (yr)
CHDCoronary heart disease, RRRelative risk
Post-treatment LDL-C level
Sever PS et al. Lancet. 20033611149-1158
51
HMG-CoA Reductase Inhibitor Secondary Prevention
Myocardial Ischemia Reduction with Aggressive
Cholesterol Lowering Trial (MIRACL)
4,162 patients with an ACS randomized to
atorvastatin (80 mg) or pravastatin (40 mg) for
24 months Acute intensive therapy
significantly reduces the event rate
17.4
Atorvastatin Placebo
14.8
Combined cardiovascular event rate ()
RR0.84, P0.048
4
8
12
16
0
Weeks
Includes death, myocardial infarction,
resuscitated cardiac arrest, recurrent
symptomatic myocardial ischemia requiring
emergency rehospitalization.
Schwartz GG et al. JAMA 20012851711-1718
52
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 Acute intensive therapy
significantly reduces the event rate
30
Atorvastatin Pravastatin
16 RRR
25
20
Recurrent MI or Cardiac Death
15
10
5
P 0.005
0
3 6 9 12 15 18 21 24 27
30
Follow-up (months)
ACSAcute coronary syndrome, CVCardiovascular,
MIMyocardial infarction, RRRRelative risk
reduction
Cannon CP et al. NEJM 20043501495-1504
53
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 Statins provide
significant benefit in those with average LDL-C
levels
30 RRR
11.5
12
8.2
8
Mortality ()
4
Plt0.001
0
Placebo
Simvastatin
MIMyocardial infarction, RRRRelative risk
reduction
4S Group. Lancet 199434413831389
54
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 Statins provide significant
benefit in those with average cholesterol levels
24 RRR
15
13.2
10.2
10
Rate of MI or CHD death ()
5
P0.003
0
Placebo
Pravastatin
CHDCoronary heart disease, MIMyocardial
infarction, RRRRelative risk reduction
Sacks FM et al. NEJM 199633510011009
55
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 Statins provide significant
benefit across a broad range of LDL-C levels
Event Rate Ratio (95 CI)
Baseline LDL-C (mg/dL) Statin (n 10,269) Placebo (n 10,267)
lt100 282 (16.4) 358 (21.0)
100129 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 (0.720.81) Plt0.0001
CADCoronary artery disease, CIConfidence
interval, DMDiabetes mellitus,
HPS Collaborative Group. Lancet 20023607-22
56
Nicotinic Acid Efficacy at Raising HDL-C
30
30
HDL-C
26
22
15
10
9
Change from Baseline
14
17
5
21
22
LDL-C
11
28
35
TG
39
44
500
1000
1500
2000
2500
Dose (mg)
3000
Goldberg A et al. Am J Cardiol 2000851100-1105
57
Fibrate Primary and Secondary Prevention
42
Rx Placebo
22
22.3
21.7
9
17.3
15.0
13.6
66
CHD Death/Nonfatal MI
13.0
34
8.0
4.1
2.7
2.7
HHS
HHS
BIP
BIP
VA-HIT
PRIMARY PREVENTION
SECONDARY PREVENTION
Post hoc analysis of subgroup with TG gt200 mg/dL
and HDL-C lt42 mg/dL. Post hoc analysis of
subgroup with TG ?200 mg/dL and HDL-C lt35
mg/dL. Difference between placebo and Rx for
primary endpoint was statistically significant (p
lt 0.05).
Frick MH et al. NEJM 19873171237-1245 Manninen
V et al. Circulation 19928537-45 BIP Study
Group. Circulation 200010221-27 Rubins HB et
al. NEJM 1999341410-418
58
Cigarette Smoking Cessation Guidelines
Complete cessation No environmental tobacco
smoke exposure
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 patients 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.
59
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 Maintenance (8 weeks, but may be used up to 6 months) 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 4 weeks 2 weeks 2 weeks 8 weeks Apply to different hairless site daily. Remove before bed for insomnia. Start at lt15 mg for lt10 cigs/day
Pharmacotherapy combined with behavioral support
provides the best success rate
Other nicotine replacement therapy options
include nicotine gum, lozenge, inhaler, nasal
spray
60
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 Bupropion with or without
NRT provides the greatest benefit
Placebo (n160) NRT (n244) Bupropion (n244) Nicotine patch and Bupropion (n245)
Abstinence rate at 6 months 18.8 21.3 34.8a,b 38.8a,c,d
Abstinence rate at 12 months 15.6 16.4 30.3a,c 35.5a,c,e
NRTNicotine replacement therapy
aplt0.001 when compared to placebo bp0.001 when
compared to NRT cplt0.001 when compared to
NRT dp0.37 when compared to buproprion ep0.22
when compared to buproprion
Jorenby DE et al. NEJM 1999340685-91
61
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.
JAMA 200629647-55 and JAMA 200629656-63
62
Weight Management Guidelines
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 lt35 inches Men
lt40 inches
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.
10 weight reduction within the first year of
therapy
BMIBody mass index
BMI is calculated as the weight in kilograms
divided by the body surface area in meters2.
Overweight state is defined by BMI25-30 kg/m2.
Obesity is defined by a BMI gt30 kg/m2.
63
Prevalence of Obesity in U.S. Adults
1996
2003
State Population No Data
lt10 1014 1519
2024 25
Source CDC Overweight and Obesity
64
CV Risk Increases with Body Mass Index
CVCardiovascular
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 200433751-758
65
Diabetes Mellitus Guidelines

• 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)
• Hypoglycemic therapy to achieve normal to near
  normal fasting plasma glucose as defined by the
  HbA1C (lt7)
• Weight reduction and exercise
• Oral hypoglycemic agents
• Insulin therapy
• Coordination of diabetic care with the patients
  primary physician and/or endocrinologist.

Goal HbA1C lt7
CVCardiovascular, DMDiabetes mellitus,
HbA1CGlycosylated hemoglobin
66
The Metabolic Syndrome

• Consists of a constellation of major risk
  factors, life-habit 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

67
ATP III Definition of the Metabolic Syndrome
Defined by presence of gt3 risk factors
Risk Factor Defining Level
Waist circumference (abdominal obesity) gt40 in (gt102 cm) in men
gt35 in (gt88 cm) in women
Triglyceride level gt150 mg/dl
HDL-C level lt40 mg/dl in men
lt50 mg/dl in women
Blood pressure gt130/gt85 mmHg
Fasting glucose gt100 mg/dl
HDL-CHigh-density lipoprotein cholesterol
Expert Panel on Detection, Evaluation, and
Treatment of High Blood Cholesterol in Adults.
JAMA 20012852486-2497
68
Metabolic Syndrome Risk of Developing DM
Finnish Diabetes Prevention Study
522 overweight (mean BMI31 kg/m2) patients with
impaired fasting glucose randomized to
intervention or usual care for 3.2
years Lifestyle modification reduces the
risk of developing DM
Intervention Control
23
11
with Diabetes Mellitus
Defined as a glucose gt140 mg/dl 2 hours after an
oral glucose challenge
Aimed at reducing weight (gt5), total intake of
fat (lt30 total calories) and saturated fat (lt10
total calories) increasing uptake of fiber (gt15
g/1000 cal) and physical activity (moderate at
least 30 min/day)
Tuomilehto J et al. NEJM 20013441343-1350
69
Metabolic Syndrome Risk of Developing DM
Diabetes Prevention Program (DPP)
3,234 patients with elevated fasting and
post-load glucose levels randomized to placebo,
metformin (850 mg twice daily), or lifestyle
modification for 2.8 years Lifestyle
modification reduces the risk of developing DM
Placebo Metformin Lifestyle modification
40
30
20
Incidence of DM ()
10
0
0
1
4
2
3
0
Years
Includes 7 weight loss and at least 150 minutes
of physical activity per week
Knowler WC et al. NEJM 2002346393-403
70
Exercise Guidelines

• 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.

Minimum 30 minutes, 5 days per week Optimal 30
minutes daily
71
Ejection Fraction Guidelines
Secondary Prevention
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-ACSNon-ST-segment elevation acute coronary
syndrome, STEMIST-segment elevation myocardial
infarction
Includes use of an aldosterone antagonist,
digitalis, and/or an implantable cardioverter
defibrillator
72
Digitalis Recommendations
Secondary Prevention
Digitalis in those with symptomatic HF and LVSD
(EF lt45) to reduce hospitalizations for
HF. Digitalis in those with asymptomatic LVSD
and normal sinus rhythm.
EFEjection fraction, HFHeart failure, LVSDLeft
ventricular systolic function
Contraindications include significant sinus or
atrioventricular block unless a permanent
pacemaker is present.
73
Relationship Between EF and Mortality
50
lt30
40
30
Cardiac Mortality
31-35
20
36-45
10
46-53
54-60
gt60
0
Ejection Fraction ()
EFEjection fraction
Post myocardial infarction
Brodie B et al. Am J Cardiol 1992691113
74
Aldosterone Antagonist Secondary Prevention
Randomized Aldactone Evaluation Study (RALES)
1,663 patients with NYHA Class III or IV HF and
LVSD (EF lt0.35) randomized to spironolactone (25
mg) or placebo (50 mg) for 24 months Aldo
sterone inhibition provides significant benefit
in patients with advanced heart failure
1.00
Spironolactone Placebo
.90
.80
Survival ()
.70
.60
.50
RR 0.70, Plt0.001
0
36
33
30
27
24
21
18
15
12
9
6
3
0
Months
EFEjection fraction, HFHeart failure, LVSDLeft
ventricular systolic dysfunction, NYHANew York
Heart Association
Pitt B et al. NEJM 1999341709-717
75
Aldosterone Antagonist Secondary Prevention
Eplerenone Poct-Acute Myocardial Infarction Heart
Failure Efficacy and Survival Study (EPHESUS)
3,313 patients with evidence of heart failure and
LVSD (EF lt0.40) after a MI randomized to
eplerenone (50 mg) or placebo for 16
months Aldosterone inhibition provides
significant benefit in patients with post-MI
heart failure and LVSD
Eplerenone Placebo
All Cause Mortality ()
RR 0.85, P0.008
Month
EFEjection fraction, LVSDLeft ventricular
systolic dysfunction, MIMyocardial infarction
Pitt B et al. NEJM 20033481309-21
76
ICD Algorithm
At least one month following a myocardial
infarction
EF lt 30
EF 31-40

EF gt 40
No
Yes
EPS

-
EFEjection fraction, EPSElectrophysiology
study, ICDImplantable cardioverter
defibrillator, RxTreatment, SCDSudden cardiac
death,
NEJM 3491836,2003
77
ICD Secondary Prevention
Overall death
75
73
Arrhythmic death
61
55
54
Mortality Reduction w/ ICD Rx
31
1
2
3
39 Months
27 Months
20 Months
EF lt35
EF lt40
EF lt30
Primary prevention of sudden cardiac death
1 Moss AJ. N Engl J Med. 19963351933-1940 2
Buxton AE. N Engl J Med. 19993411882-1890 3
Moss AF. N Engl J Med. 2002346877-883
78
Prevention Pyramid
Secondary
Primary
Primordial
ACE-1 angiotensin converting enzyme inhibitor
ASA aspirin