Transcript 2006 AHA Secondary Prevention Guidelines Slide Set

AHA/ACC Guidelines for Secondary
Prevention for Patients with Coronary and
Other Atherosclerotic Vascular Disease:
2006 Update
Gregg C. Fonarow, MD and Sidney Smith Jr, MD on
behalf of the Secondary Prevention Writing Group
2
Introduction
This slide set was adapted from the AHA/ACC Secondary
Prevention for Patients with Coronary and Other
Atherosclerotic Vascular Disease: 2006 Update
The full-text guidelines are available on the Web sites of
the AHA (www.americanheart.org) and the ACC
(www.acc.org)
Circulation 2006;113:2363-2372 and J Am Coll Cardiol 2006;47:2130-2139
3
Introduction
• Since the 2001 update of the AHA/ACC consensus
statement on secondary prevention, important evidence
from clinical trials has emerged that further supports and
broadens the merits of aggressive risk reduction therapies
• This growing body of evidence confirms that aggressive
comprehensive risk factor management improves survival,
reduces recurrent events and the need for interventional
procedures, and improves the quality of life
• The secondary prevention patient population includes
those with established coronary and other atherosclerotic
vascular disease, including peripheral arterial disease,
atherosclerotic aortic disease and carotid artery disease.
4
AHA Secondary Prevention for Patients with
Coronary Artery and Other Atherosclerotic
Vascular Disease Writing Committee Members
Sidney C. Smith, Jr, MD; Jerilyn Allen, RN, ScD; Steven N. Blair,
PED; Robert O. Bonow, MD; Lawrence M. Brass, MD; Gregg C.
Fonarow, MD; Scott M. Grundy, MD, PhD; Loren Hiratzka, MD ;
Daniel Jones, MD; Harlan M. Krumholz, MD; Lori Mosca, MD, PhD,
MPH; Richard C. Pasternak, MD*; Thomas Pearson, MD, MPH,
PhD; Marc A. Pfeffer, MD, PhD; Kathryn A. Taubert, PhD
Circulation 2006;113:2363-2372 and J Am Coll Cardiol 2006;47:2130-2139
*Dr. Pasternak withdrew from the Writing Group on June 22nd, 2004, when he accepted an offer of
employment as Vice President, Clinical Research, Cardiovascular and Atherosclerosis at Merck Research
Laboratories.
5
Applying Classification of
Recommendations and Level of
Evidence
Class I
Class IIa
Class IIb
Class III
Benefit >>> Risk
Benefit >> Risk
Additional studies
with focused
objectives needed
Benefit ≥ Risk
Additional studies
with broad
objectives needed;
Additional registry
data would be
helpful
Risk ≥ Benefit
No additional studies
needed
Procedure or
treatment SHOULD
be performed or
administered
IT IS REASONABLE
to perform
procedure or
administer
treatment
Procedure or
treatment
MAY BE
CONSIDERED
Procedure or
treatment should
NOT be performed or
administered SINCE
IT IS NOT HELPFUL
AND MAY BE
HARMFUL
6
Applying Classification of
Recommendations and Level of
Evidence
Level A
Class I
Class IIa
Class IIb
Class III
Multiple (3-5)
population risk
strata evaluated
Recommendation
that procedure
or treatment is
useful/ effective
Recommendation
in favor of
treatment or
procedure being
useful/ effective
Recommendation’
s usefulness/
efficacy less well
established
Recommendation
that procedure
or treatment not
useful/ effective
and may be
harmful
General
consistency of
direction and
magnitude of
effect
Sufficient
evidence from
multiple
randomized
trials or metaanalyses
Some conflicting
evidence from
multiple
randomized
trials or metaanalyses
Greater
conflicting
evidence from
multiple
randomized
trials or metaanalyses
Sufficient
evidence from
multiple
randomized
trials or metaanalyses
7
Applying Classification of
Recommendations and Level of
Evidence
Level B
Limited (2-3)
population risk
strata evaluated
Class I
Class IIa
Class IIb
Recommendation that
procedure or
treatment is
useful/ effective
Recommen-dation
in favor of
treatment or
procedure being
useful/ effective
Recommendation’s
usefulness/
efficacy less well
established
Limited evidence
from single
randomized trial
or nonrandomized
studies
Some conflicting
evidence from
single
randomized trial
or nonrandomized
studies
Greater conflicting
evidence from
single
randomized trial
or nonrandomized
studies
Class III
Recommen-dation
that procedure or
treatment not
useful/effective
and may be
harmful
Limited evidence
from single
randomized trial
or nonrandomized
studies
8
Applying Classification of
Recommendations and Level of
Evidence
Level C
Very limited (1-2)
population risk
strata evaluated
Class I
Recommendation that
procedure or
treatment is
useful/ effective
Only expert
opinion, case
studies, or
standard-ofcare
Class IIa
Class IIb
Recommendation
in favor of
treatment or
procedure being
useful/effective
Recommendation’s
usefulness/
efficacy less well
established
Only diverging
expert opinion,
case studies, or
standard-of-care
Only diverging
expert opinion,
case studies, or
standard-of-care
Class III
Recommendation
that procedure or
treatment not
useful/effective
and may be
harmful
Only expert
opinion, case
studies, or
standard-of-care
9
Secondary Prevention Definition
• Therapy to reduce recurrent cardiovascular events and
decrease cardiovascular mortality in patients with
established atherosclerotic vascular disease
• Patients covered include those with established
coronary and other atherosclerotic vascular disease,
including peripheral arterial disease, atherosclerotic aortic
disease and carotid artery disease
• Individuals with sub-clinical atherosclerosis and patients
whose only manifestation is diabetes are covered in other
guidelines
10
Components of Secondary
Prevention
Cigarette smoking cessation
Blood pressure control
Lipid management to goal
Physical activity
Weight management to goal
Diabetes management to goal
Antiplatelet agents / anticoagulants
Renin angiotensin aldosterone system blockers
Beta blockers
Influenza vaccination
11
Evidence Based Therapies
The writing group emphasizes the importance of giving
consideration to the use of cardiovascular medications
that have been proven to be of benefit in randomized
clinical trials.
This approach strengthens the evidence-based
foundation for therapeutic application of these
guidelines.
The committee acknowledges that in many trials there is
under-representation of ethnic minorities, women, and
the elderly.
12
Cigarette Smoking
Recommendations
Goal: Complete Cessation and No
Exposure to Environmental
Tobacco Smoke
•Ask about tobacco use status at every visit.
•Advise every tobacco user to quit.
•Assess the tobacco user’s willingness to quit.
I IIa IIb III
•Assist by counseling and developing a plan for
quitting.
•Arrange follow-up, referral to special programs,
or pharmacotherapy (including nicotine
replacement and bupropion.
•Urge avoidance of exposure to environmental
tobacco smoke at work and home.
13
Cigarette Smoking Cessation: Risk
of Non-fatal MI*
RR (95% Cl)
Study
Aberg, et al. 1983
0.67 (0.53-0.84)
Herlitz, et al. 1995
0.99 (0.42-2.33)
Johansson, et al. 1985
0.79
Perkins, et al. 1985
3.87 (0.81-18.37)
Sato, et al. 1992
0.10 (0.00-1.95)
Sparrow, et al. 1978
0.76 (0.37-1.58)
Vlietstra, et al. 1986
0.63 (0.51-0.78)
Voors, et al. 1996
0.54 (0.29-1.01)
0.1
Ceased smoking
*Includes those with known coronary heart disease
Critchley JA et al. JAMA. 2003;290:86-97.
1.0
Continued smoking
(0.46-1.37)
10
CI=Confidence interval, RR=Relative risk
14
Smoking Cessation Algorithm
Ask and document pt’s
tobacco use status
Current User
Recent Quitter
(<6 months)
Advise: Provide a strong, personalized
message to quit using tobacco
Assess* readiness to quit in next 30 days
Prevent Relapse
• Congratulate successes
• Encourage to remain tobacco-free
• Discuss benefits experienced by patient
• Address weight gain, negative mood, and lack of support
Not Ready
Ready
Assist
• Negotiate a plan
• STAR**
• Discuss pharmacotherapy
• Social support
• Provide educational materials
Arrange follow-up to check plan or adjust meds
• Call right before and after quit date
• Weekly follow-up x 2 weeks, then monthly x 6 months
• Ask about difficulties (withdrawal, depressed mood)
• Build upon successes
• Seek commitment to stay tobacco-free
Increase Motivation
• Relevance to patients personal situation
• Risks: short and long term, environmental
• Rewards: potential benefits of quitting
• Roadblocks: identify barriers and potential
solutions
• Repetition: repeat motivational intervention
• Reassess readiness to quit
**STAR
Set quit date
Tell family, friends, and coworkers about it
Anticipate challenges: withdrawal, breaks
Remove tobacco from the house, car, and
social life
Treating Tobacco Use and Dependence: A
Clinical Practice Guideline, U.S. Department of
Health and Human Services, June 2000
15
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.
Within 2 weeks of
a MI
Unstable angina
Arrhythmias
Decompensated
heart failure
Skin
reaction
Insomnia
Transdermal
Nicotine
Patch**
21 mg QAM
14 mg QAM
7 mg QAM
or
15 mg QAM
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
*Pharmacotherapy combined with behavioral support provides the best success rate
**Other nicotine replacement therapy options include: nicotine gum, lozenge, inhaler, nasal spray
16
Blood Pressure Control
Recommendations
Goal: <140/90 mm Hg or <130/80 if
diabetes or chronic kidney disease
I IIa IIb III
I IIa IIb III
Blood pressure 120/80 mm Hg or greater:
Initiate or maintain lifestyle modification: weight control,
increased physical activity, alcohol moderation, sodium
reduction, and increased consumption of fresh fruits
vegetables and low fat dairy products
Blood pressure 140/90 mm Hg or greater (or 130/80
or greater for chronic kidney disease or diabetes)
As tolerated, add blood pressure medication, treating
initially with beta blockers and/or ACE inhibitors with
addition of other drugs such as thiazides as needed to
achieve goal blood pressure
17
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
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
120 140 160 180
Usual Systolic BP (mm Hg)
70 80 90 100 110
Usual Diastolic BP (mm Hg)
BP=Blood pressure
Prospective Studies Collaboration. Lancet. 2002;360:1903-1913
18
Blood Pressure: Risk of CHD with
Active Treatment
Veterans Administration, 1967
Veterans Administration, 1970
Hypertension Stroke Study, 1974
USPHS Study, 1977
EWPHE Study, 1985
Coope and Warrender, 1986
SHEP Study, 1991
STOP-Hypertension Study, 1991
MRC Study, 1992
Syst-Eur Study, 1997
0.79
(0.69 to 0.90)
Total
0
CHD=Coronary heart disease
He J et al. Am Heart J 1999; 138:211-219
0.5
1.0
1.5
2.0
Better than placebo Worse than placebo
19
JNC VII Guidelines for Management
and Treatment
Initial drug therapy
BP
classification
SBP*
mmHg
DBP*
mmHg
Lifestyle
modification
<120
<80
Encourage
Prehypertension
120–139
80–89
Yes
Stage 1
Hypertension
140–159
90–99
Yes
>100
Yes
Normal
Stage 2
Hypertension
>160
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.
20
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
21
JNC VII Compelling Indications for
Drug Classes
Compelling Indication
Initial Therapy Options
Clinical-Trial Basis
Heart Failure
Diuretic, BB, ACEI,
ARB, Aldo Ant
MERIT-HF, COPERNICUS, CIBIS,
SOLVD, AIRE, TRACE, Val-HeFT,
RALES
Post-MI
BB, ACEI, Aldo Ant
ACC/AHA Post-MI Guideline,
BHAT, SAVE, Capricorn,
EPHESUS
High CAD Risk
Diuretic, BB, ACEI, CCB
ALLHAT, HOPE, ANBP2,
LIFE, CONVINCE
Diabetes Mellitus
Chronic Kidney
Disease
Recurrent Stroke Prevention
Diuretic, BB, ACEI,
ARB, CCB
NKF-ADA Guideline,
UKPDS, ALLHAT
ACEI, ARB
NKF Guideline, Captopril
Trial, RENAAL, IDNT, REIN,
AASK
Diuretic, ACEI
PROGRESS
ACEI=Angiotensin converting enzyme inhibitor, Aldo Ant=Aldosterone antagonist, ARB=Angiotensin
receptor blocker, BB=b-blocker, CAD=Coronary artery disease, CCB=Calcium channel blocker,
MI=Myocardial Infarction
Chobanian AV et al. JAMA. 2003;289:2560-2572
22
Lipid Management Goal
I IIa IIb III
LDL-C should be less than 100 mg/dL
I IIa IIb III
Further reduction to LDL-C to < 70 mg/dL
is reasonable
If TG >200 mg/dL, non-HDL-C should be < 130 mg/dL*
*Non-HDL-C = total cholesterol minus HDL-C
23
Lipid Management Goals: NCEP
Risk Category
High risk:
CHD or CHD risk
equivalents
(10-year risk >20%)
and
Very high risk:
ACS or established CHD
plus: multiple major risk
factors (especially
diabetes) or severe and
poorly controlled risk
factors
Consider
Drug Therapy
LDL-C and nonHDL-C Goal
Initiate TLC
<100 mg/dL
if TG > 200 mg/dL,
non-HDL-C
should be < 130
mg/dL
100
mg/dL
>100 mg/dL
(<100 mg/dL: consider
drug options)
<70 mg/dL,
non-HDL-C < 100
mg/dL
All patients
>100 mg/dL
(<100 mg/dL: consider
drug options)
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.
24
Lipid Management
Recommendations
For all patients
I IIa IIb III
Start dietary therapy (<7% of total calories as
saturated fat and <200 mg/d cholesterol)
Adding plant stanol/sterols (2 gm/day) and
viscous fiber (>10 mg/day) will further lower LDL
I IIa IIb III
Promote daily physical activity and weight
management.
I IIa IIb III
Encourage increased consumption of omega-3
fatty acids in fish or 1 g/day omega-3 fatty acids
in capsule form for risk reduction.
25
ATP III Dietary Recommendations
Nutrient
Saturated fat*
Recommended Intake
<7% of total calories
Polyunsaturated fat
Up to 10% of total calories
Monounsaturated fat
Up to 20% of total calories
Total fat
25%–35% of total calories
Carbohydrate (esp. complex carbs)
Fiber
50%–60% of total calories
20–30 g/d
Protein
Cholesterol
~15% of total calories
<200 mg/d
*Trans fatty acids also raise LDL-C and should be kept at a low intake.
Note: Regarding total calories, balance energy intake and expenditure to maintain
desirable body weight.
ATP=Adult Treatment Panel
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA
2001;285:2486-2497.
26
Lipid Management
Recommendations
Assess fasting lipid profile in all patients, and within 24 hours of
hospitalization for those with an acute event. For patients hospitalized,
initiate lipid-lowering medication as recommended below prior to discharge
according to the following schedule:
I IIa IIb III
If baseline LDL-C > 100 mg/dL, initiate LDLlowering drug therapy
I IIa IIb III
If on-treatment LDL-C > 100 mg/dL,
intensify LDL-lowering drug therapy (may
require LDL lowering drug combination)
I IIa IIb III
If baseline is LDL-C 70 to 100 mg/dL, it is
reasonable to treat to LDL < 70 mg/dL
When LDL lowering medications are used, obtain at least a 30-40% reduction in LDL-C
levels.
27
Lipid Management
Recommendations
I IIa IIb III
If TG are 200-499 mg/dL, non-HDL-C should be
< 130 mg/dL
I IIa IIb III
Further reduction of non-HDL to < 100 mg/dL
is reasonable
Therapeutic options to reduce non-HDL-C:
More intense LDL-C lowering therapy I (B) or
Niacin (after LDL-C lowering therapy) IIa (B) or
Fibrate (after LDL-C lowering therapy) IIa (B)
I IIa IIb III
If TG are > 500 mg/dL, therapeutic options to
prevent pancreatitis are fibrate or niacin
before LDL lowering therapy; and treat LDL-C
to goal after TG-lowering therapy. Achieve
non-HDL-C < 130 mg/dL, if possible
28
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
CAD=Coronary artery disease, CI=Confidence interval, DM=Diabetes mellitus,
HPS Collaborative Group. Lancet 2002;360:7-22
29
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)
ACS=Acute coronary syndrome, CV=Cardiovascular, MI=Myocardial infarction, RRR=Relative risk
reduction
Cannon CP et al. NEJM 2004;350:1495-1504
30
HMG-CoA Reductase Inhibitor:
Secondary Prevention
Relationship between LDL Levels and Event Rates in
Secondary Prevention Trials of Patients with Stable CHD
30
4S
Statin
Placebo
Event (%)
25
4S
20
LIPID
15
LIPID
CARE
10
HPS
5
0
CARE
HPS
TNT (atorvastatin 10 mg/d)
TNT (atorvastatin 80 mg/d)
0
70
90
110
130
150
LDL-C (mg/dL)
170
190
210
LDL-C=Low density lipoprotein cholesterol; TNT=Treating to New Targets; HPS=Heart Protection
Study; CARE=Cholesterol and Recurrent Events Trial; LIPID=Long-term Intervention with Pravastatin
in Ischaemic Disease; 4S=Scandinavian Simvastatin Survival Study.
LaRosa JC et al. NEJM. 2005;352:1425-1435
31
Lipid Management
Pharmacotherapy
TC
LDL
HDL
TG
Patient
tolerability
 19-37%
 25-50%
4-12%
 14-29%
Good
 13%
18%
1%
 9%
Good
Bile acid
sequestrants
7-10%
10-18%
3%
Neutral or
Poor
Nicotinic acid
 10-20%
 10-20%
14-35%
 30-70%
Reasonable
to Poor
19%
4-21%
11-13%
30%
Good
Therapy
Statins*
Ezetimibe
Fibrates
HDL-C=High-density lipoprotein cholesterol, LDL-C=Low-density lipoprotein cholesterol, TC=Total
cholesterol, TG=Triglycerides
*Daily dose of 40mg of each drug, excluding rosuvastatin.
32
Physical Activity Recommendations
Goal: 30 minutes 7 days/week,
minimum 5 days/week
I IIa IIb III
Assess risk with a physical activity history
and/or an exercise test, to guide prescription
I IIa IIb III
I IIa IIb III
Encourage 30 to 60 minutes of moderate
intensity aerobic activity such as brisk
walking, on most, preferably all, days of the
week, supplemented by an increase in daily
lifestyle activities
Advise medically supervised programs for
high-risk patients (e.g. recent acute coronary
syndrome or revascularization, HF)
33
Exercise Evidence: Mortality Risk
Observational study of self-reported physical activity in 772 men
with established coronary heart disease
Light or moderate exercise is associated with lower risk
Wannamethee SG et al. Circulation 2000;102:1358-1363
34
Weight Management Recommendations
Goal: BMI 18.5 to 24.9 kg/m2
Waist Circumference: Men: < 40 inches
Women: < 35 inches
I IIa IIb III
I IIa IIb III
I IIa IIb III
Assess BMI and/or waist circumference on each visit
and consistently encourage weight maintenance/
reduction through an appropriate balance of physical
activity, caloric intake, and formal behavioral programs
when indicated.
If waist circumference (measured at the iliac crest)
>35 inches in women and >40 inches in men initiate
lifestyle changes and consider treatment strategies for
metabolic syndrome as indicated.
The initial goal of weight loss therapy should be to
reduce body weight by approximately 10 percent from
baseline. With success, further weight loss can be
attempted if indicated.
*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.
35
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
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
36
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
Grundy, et al. Diagnosis and management of the metabolic syndrome: an
AHA/NHLBI Scientific Statement. Circulation 2005;112:2735-2752.
37
Metabolic Syndrome: Risk of
Developing DM
Diabetes Prevention Program (DPP)
Incidence of DM (%)
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
Placebo
Metformin
Lifestyle modification
40
20
0
1
2
3
4
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
38
Diabetes Mellitus Recommendations
Goal: Hb A1c < 7%
I IIa IIb III
Lifestyle and pharmacotherapy to achieve near
normal HbA1C (<7%).
I IIa IIb III
Vigorous modification of other risk factors (e.g.,
physical activity, weight management, blood
pressure control, and cholesterol management as
recommended).
I IIa IIb III
Coordinate diabetic care with patient’s primary
care physician or endocrinologist. )
HbA1c = Glycosylated hemoglobin
39
Antiplatelet Agents / Anticoagulation
Recommendations
40
Aspirin Recommendations
I IIa IIb III
Start and continue indefinitely aspirin 75 to
162 mg/d in all patients unless
contraindicated
I IIa IIb III
For patients undergoing CABG, aspirin (100 to
325 mg/d) should be started within 48 hours
after surgery to reduce saphenous vein graft
closure
I IIa IIb III
Post-PCI-stented patients should receive 325
mg per day of aspirin for 1 month for bare
metal stent, 3 months for sirolimus-eluting
stent and 6 months for paclitaxel-eluting stent
41
Clopidogrel Recommendations
Start and continue clopidogrel 75 mg/d
in combination with aspirin
I IIa IIb III
for post ACS or post PCI with stent
placement patients for up to 12
months
for post PCI-stented patients
>1 month for bare metal stent,
>3 months for sirolimus-eluting stent
>6 months for paclitaxel-eluting stent
*Clopidogrel is generally given preference over Ticlopidine because of a superior safety profile
42
Anticoagulation Recommendations
I IIa IIb III
I IIa IIb III
Manage warfarin to international normalized
ratio 2.0 to 3.0 for paroxysmal or chronic
atrial fibrillation or flutter, and in post-MI
patients when clinically indicated (e.g., atrial
fibrillation, LV thrombus.)
Use of warfarin in conjunction with aspirin
and/or clopidogrel is associated with
increased risk of bleeding and should be
monitored closely
43
Aspirin Evidence: Secondary
Prevention
Effect of antiplatelet therapy* on vascular events**
Category
% Odds Reduction
Acute myocardial infarction
Acute stroke
Prior myocardial infarction
Prior stroke/transient ischemic attack
Other high risk
Coronary artery disease
(e.g. unstable angina, heart failure)
Peripheral arterial disease
(e.g. intermittent claudication)
High risk of embolism (e.g. atrial fibrillation)
Other (e.g. diabetes mellitus)
All trials
0.0
0.5
1.0
1.5
2.0
Antiplatelet better Control better
*Aspirin was the predominant antiplatelet agent studied
**Vascular events include MI, stroke, or death
Antithrombotic Trialist Collaboration. BMJ 2002;324:71–86.
44
Aspirin Evidence: Dose and
Efficacy
Indirect Comparisons of Aspirin Doses on Vascular Events
in High-Risk Patients
Aspirin Dose
No. of Trials
(%)
500-1500 mg
34
19
160-325 mg
19
26
75-150 mg
12
32
<75 mg
3
13
Any aspirin
65
23
0
Odds Ratio for
Vascular Events
P<.0001
0.5
Antiplatelet Better
Antithrombotic Trialists Collaboration. BMJ. 2002;324:71-86
1.0
1.5
2.0
Antiplatelet Worse
45
Clopidogrel Evidence: ACS
(Non-STEMI and UA)
Clopidogrel in Unstable Angina to Prevent Recurrent Events
(CURE) Trial
Rate of death,
myocardial infarction,
or stroke
12,562 patients with a NSTEMI-ACS randomized to daily aspirin (75325 mg) or clopidogrel (300 mg load, 75 mg thereafter) plus
aspirin (75-325 mg) for 3-12 months (average 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
9
12
Months of Follow Up
NSTEMI-ACS=Non ST-segment elevation acute coronary syndrome
The CURE Trial Investigators. NEJM. 2001;345:494-502
46
Clopidogrel Evidence: Post PCI
Clopidogrel for the Reduction of Events during Observation
(CREDO) Trial
Risk of MI, Stroke,
or Death (%)
2,116 patients undergoing PCI randomized to 4 weeks of DAP*
followed by aspirin (75-325 mg) monotherapy vs persistent
DAP* for 1 year
15
4 weeks of DAP
1 year of DAP
10
5
27% RRR, P=0.02
00
3
6
Months from Randomization
9
12
DAP=Dual antiplatelet therapy, PCI=Percutaneous coronary intervention, RRR=Relative risk reduction
*Dual antiplatelet therapy=Aspirin (75-325 mg daily) plus Clopidogrel (300 mg load followed by 75 mg
daily).
Steinhubl S et al. JAMA 2002; 288:2411-20
47
Renin-Angiotensin-Aldosterone
System Blockers Recommendations
48
ACE Inhibitor Recommendations
I IIa IIb III
Use in all patients with LVEF < 40%, and
those with diabetes or chronic kidney
disease indefinitely, unless contraindicated
I IIa IIb III
Consider for all other patients
I IIa IIb III
Among lower risk patients with normal LVEF
where cardiovascular risk factors are well
controlled and where revascularization has
been performed, their use may be
considered optional
ACE=Angiotensin converting enzyme, LVEF= left ventricular ejection fraction
49
Angiotensin Receptor Blocker
Recommendations
I IIa IIb III
I IIa IIb III
Use in patients who are intolerant of ACE
inhibitors with HF or post MI with LVEF less
than or equal to 40%.
Consider in other patients who are ACE
inhibitor intolerant.
I IIa IIb III
Consider use in combination with ACE
inhibitors in systolic dysfunction HF.
ACE=Angiotensin converting enzyme inhibitor, LVEF=Left Ventricular Ejection fraction, HF=Heart
failure, MI=Myocardial infarction
50
Aldosterone Antagonist
Recommendations
I IIa IIb III
Use in post MI patients, without significant
renal dysfunction or hyperkalemia, who are
already receiving therapeutic doses of an
ACE inhibitor and beta blocker, have an LVEF
< 40% and either diabetes or heart failure
*Contraindications include abnormal renal function (creatinine >2.5
mg/dL in men or >2.0 mg/dL in women) and hyperkalemia (K+ >5.0
meq/L)
ACE=Angiotensin converting enzyme inhibitor, LVEF=Left Ventricular Ejection fraction,
MI=Myocardial infarction
51
ACE Inhibitor Evidence: Post MI
with LVD or HF
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=Angiotensin converting enzyme inhibitors, LVSD=Left ventricular systolic dysfunction,
MI=Myocardial infarction, OR=Odds ratio
Flather MD, et al. Lancet. 2000;355:1575–1581
52
ACE Inhibitor Evidence: CAD, CVD,
PVD or DM
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=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
53
ACE Inhibitor Evidence: CAD
European Trial on Reduction of Cardiac Events with Perindopril
in Stable Coronary Artery Disease (EUROPA)
13,655 patients with CAD and presumed normal left ventricular
function randomized to perindopril (8 mg) or placebo for 4.2 years
Cardiovascular death (0.86; 0.72-1.03)
Non-fatal MI (0.78; 0.20-0.90)
Cardiac arrest (0.54; 0.20-1.47)
Combined endpoint (0.80; 0.71-0.91)
0
0.5
1
Favors Perindopril
1.5
2
Favors Placebo
ACE-I=Angiotensin converting enzyme inhibitors, CAD=Coronary artery disease, CV=Cardiovascular,
MI=Myocardial infarction
EUROPA Investigators. Lancet 2003;362:782-788
54
ACE Inhibitor Evidence: CAD
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
4.8 years
Primary End Point (%)*
30
Placebo
Trandolapril
25
20
15
10
5
0
0
1
2
3
4
5
6
Years After Randomization
*Includes death from cardiovascular causes, myocardial infarction, or coronary revascularization
PEACE Trial Investigators. NEJM 2004;351:2058-2068
55
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
*Reflects greater blood pressure control, revascularization, 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.
56
ARB Evidence: Post MI with LVD
or HF
Valsartan in Acute Myocardial Infarction Trial (VALIANT)
14,703 patients with post-MI HF or LVSD (EF <0.40) randomized to
captopril (50 mg three times daily), valsartan (160 mg twice daily), or
captopril (50 mg three times daily) plus valsartan (80 mg twice daily)
over 2 years
0.4
All Cause Mortality
Captopril
Valsartan
0.3
Valsartan and Captopril
0.2
0.1
Valsartan vs. Captopril: HR = 1.00; P = 0.982
Valsartan + Captopril vs. Captopril: HR = 0.98; P = 0.726
0.0
0
6
12
18
24
30
36
Months
EF=Ejection fraction, HR=Hazard ratio, LVSD=Left ventricular systolic dysfunction, MI=Myocardial
infarction, RAS=Renin angiotensin system
Pfeffer M et al. NEJM 2003;349:1893-1906.
57
ARB Evidence: Heart Failure
Candesartan in Heart Failure Assessment of Reduction in
Mortality and Morbidity (CHARM) Alternative Trial
2,028 patients with symptomatic HF, LVSD (EF <40%), and
intolerance to ACE-I randomized to candesartan (32 mg) or
placebo over 34 months
CV Death of
Hospitalization
for HF
50
Placebo
40
Candesartan
30
20
10
HR 0.77 p=0.0004
0
0
1
2
Years
3
ACE-I=Angiotensin converting enzyme inhibitors, ARB=Angiotensin receptor blockers, EF=Ejection
fraction, HF=Heart failure, LVSD=Left ventricular systolic dysfunction
Granger CB et al. Lancet. 2003;362:772-777
58
ARB Evidence: Heart Failure
Candesartan in Heart Failure Assessment of Reduction in
Mortality and Morbidity (CHARM) Added Trial
2,548 patients with symptomatic HF and LVSD (EF <40%)
randomized to candesartan (32 mg) or placebo in addition to
an ACE-I over 34 months
CV Death of
Hospitalization
for HF
50
Placebo
40
Candesartan
30
20
10
HR 0.85, p=0.011
0
0
1
2
Years
3
3.5
ACE-I=Angiotensin converting enzyme inhibitors, ARB=Angiotensin receptor blockers, EF=Ejection
fraction, HF=Heart failure, LVSD=Left ventricular systolic dysfunction, RAS=Renin angiotensin
system
McMurray JJ et al. Lancet. 2003;362:767-71
59
Aldosterone Antagonist: Heart
Failure
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
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
60
Aldosterone Antagonist: Post MI HF
and LVSD
Eplerenone Post-Acute Myocardial Infarction Heart Failure
Efficacy and Survival Study (EPHESUS)
All Cause Mortality (%)
6,644 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
EF=Ejection fraction, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction
Pitt B et al. NEJM 2003;348:1309-21
61
b-blocker Recommendations
62
b-blocker Recommendations
I IIa IIb III
I IIa IIb III
Start and continue indefinitely in all post MI,
ACS, LV dysfunction with or without HF
symptoms, unless contraindicated.
Consider chronic therapy for all other
patients with coronary or other vascular
disease or diabetes unless contraindicated.
*Precautions but still indicated include mild to moderate asthma or chronic obstructive pulmonary
disease, insulin dependent diabetes mellitus, severe peripheral arterial disease, and a PR
interval >0.24 seconds.
MI=Myocardial infarction, HF=Heart Failure
63
b-blocker Evidence
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
2.0
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.
64
b-blocker Evidence: Post MI with
Left Ventricular Dysfunction
Carvedilol Post-Infarct Survival Control in LV Dysfunction
(CAPRICORN)
Proportion Event-free
6,644 patients with LVEF <0.40 after a MI with or without HF
randomized to carvedilol or placebo for 24 months
1
0.95
n=975
0.9
Carvedilol
n=984
0.85
0.8
0.75
0.7
RR 0.77 P=.03
0
0.5
1
1.5
Placebo
2
2.5
Years
The CAPRICORN Investigators. Lancet. 2001;357:1385–1390.
65
b-blocker Evidence: Benefit in HF
and LVSD
Study
Drug
HF
Severity
Patients
(n)
Follow-up
(years)
Mean
Dosage
Effects on
Outcomes
CIBIS
Bisoprolol*
Moderate
-Severe
641
1.9
3.8
mg/day
All cause mortality
22% (p=NS)
CIBIS-II
Bisoprolol*
Moderate
-Severe
2,647
1.3
7.5
mg/day
All cause mortality
34% (P<0.0001)
BEST
Bucindolol*
Moderate
-Severe
2,708
2.0
152
mg/day
All cause mortality
10% (p=NS)
MERIT-HF
Metoprolol
succinate#
MildModerate
3,991
1.0
159
mg/day
All cause mortality
34% (P=0.0062)
MDC
Metprolol
tartrate*
MildModerate
383
1.0
108
mg/day
Death or Need for
Tx 30% (P=NS)
CAPRICORN
Carvedilol
Mild
1,989
1.3
40
mg/day
All cause mortality
23% (P =0.03)
US Carvedilol
Carvedilol
MildModerate
1,094
0.5
45
mg/day
All-cause
mortality†
65% (P=.0001)
COPERNICUS
Carvedilol
Severe
2,289
0.9
37
mg/day
All-cause mortality
35% (P =0.0014)
*Not an approved indication
†Not a planned end point.
#Not approved for severe HF or mortality reduction alone
66
Influenza Vaccination
I IIa IIb III
Patients with cardiovascular disease
should have influenza vaccination
67
Influenza Vaccination Evidence
Effectiveness of Influenza Vaccination during the Influenza Seasons
Vaccinated
Subjects
(N=77,738)
Unvaccinated
Subjects
(N=62,317)
Adjusted
Odds Ratio
P value
Pneumonia or influenza
495 (0.6)
581 (0.9)
0.68
(0.60–0.78)
<0.001
Cardiac disease
888 (1.1)
1026 (1.6)
0.81
(0.73–0.89)
<0.001
Ischemic heart disease
457 (0.6)
535 (0.9)
0.80
(0.70–0.91)
0.001
Heart failure
466 (0.6)
538 (0.9)
0.81
(0.70–0.92)
0.002
Cerebrovascular disease
398 (0.5)
427 (0.7)
0.84
(0.72–0.97)
0.018
Death
943 (1.2)
1361 (2.2)
0.52
(0.47–0.57)
<0.001
Hospitalization or death
2387 (3.1)
2910 (4.7)
0.65
(0.62–0.70)
<0.001
Hospitalization
Community cohort of 140,055 subjects in the 1998–1999 season of which 55.5 % were immunized.
Nichol et al. N Engl J Med 2003;348:1322-32.
68
The Need to Implement Secondary
Prevention
Multiple studies of the use of these recommended therapies in
appropriate patients continue to show that many patients in whom
therapies are indicated are not receiving them in actual clinical
practice.
The AHA and ACC urge that in all medical care settings where these
patients are managed that programs to provide practitioners with
useful reminder clues based on the guidelines, and continuously
assess the success achieved in providing these therapies to the
patients who can benefit from them be implemented.
Encourage that the AHA’s Get With the Guidelines and/or ACC’s
Guidelines Applied to Practice Programs be instituted to identify
appropriate patients for therapy
69
AHA GWTG Program
GWTG is a national initiative of the AHA to improve
guidelines adherence in patients hospitalized with
cardiovascular disease.
GWTG uses collaborative learning sessions,
conference calls, e-mail and staff support to assist
hospital teams improve acute and secondary
prevention care systems.
A web-based Patient Management Tool is used for
point of care data collection and decision support,
on-demand reporting, communication and patient
education.
70
SIMPLE, ONE PAGE, ON-LINE FORM
Demographics
6 clicks
Clinical/Lab
8 clicks
Discharge
meds and
interventions
7 clicks
Interactively
checks
patient’s
data with the
AHA guidelines
71
©2001 Outcome Sciences, Inc.
Impact of AHA Get With The
Guidelines-CAD Program on
Quality of Care
Baseline
*
100
90
80
70
60
50
40
30
20
10
0
*
* 97
9796
95
93
Q1
Q2
8787
*
64656567
Aspirin
Q4
* p< 0.05 compared to baseline
*
* * 91
83
79
Q3
68
Beta Blocker ACE Inhibitor
GWTG-CAD: 123 US Hospitals n=27,825
Labresh, Fonarow et al. Circulation 2003;108:IV-722
* *
* 75
73
6770
74
*
* * 82
* 7675
70
57
Lipid Rx
Smoking
Cessation
72
AHA Secondary Prevention for Patients
with Coronary Artery and Other
Atherosclerotic Vascular Disease
Circulation 2006;113:2363-2372 and
J Am Coll Cardiol 2006;47:2130-2139
73
Secondary Prevention Conclusions
• Evidence confirms that aggressive comprehensive
risk factor management improves survival, reduces
recurrent events and the need for interventional
procedures, and improves the quality of life for these
patients.
• Every effort should be made to ensure that patients
are treated with evidence-based, guideline
recommended, life-prolonging therapies in the
absence of contraindications or intolerance.
74
75