Download 100 mg/dL

Οδηγίες AHA/ACC για δευτερογενή
πρόληψη για ασθενείς με καρδιαγγειακή
αθηροσκληρωτική νόσο:
Αναθεώρηση 2006
1
Το πλήρες κείμενο των οδηγιών μπορείτε να το βρείτε
στο δικτυακό τόπο της AHA (www.americanheart.org)
και του ACC (www.acc.org)
Circulation 2006;113:2363-2372 and J Am Coll Cardiol 2006;47:2130-2139
2
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.
3
AHA/ACC 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
*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.
4
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
5
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
6
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
7
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
8
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
9
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
10
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.
11
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.
12
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
13
Smoking Cessation Algorithm
Ask and document pt’s
tobacco use status
Current User
Prevent Relapse
Recent Quitter
(<6 months)
Advise: Provide a strong, personalized
message to quit using tobacco
• Congratulate successes
• Encourage to remain tobacco-free
• Discuss benefits experienced by patient
• Address weight gain, negative mood, and lack of support
Increase Motivation
Assess* readiness to quit in next 30 days
Ready
Not 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
• 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
14
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
*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
15
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
16
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
Age at Risk (Y)
80-89
256
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)
17
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
18
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.
Chobanian AV et al. JAMA. 2003;289:2560-2572
19
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
Moderate alcohol
consumption
<2 drinks/day for men and <1
drink/day for women
2-4 mmHg
Adopt DASH
eating plan
BMI=Body mass index, SBP=Systolic blood pressure
Chobanian AV et al. JAMA. 2003;289:2560-2572
20
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
Diuretic, BB, ACEI,
ARB, CCB
Chronic Kidney Disease
ACEI, ARB
Recurrent Stroke Prevention
Diuretic, ACEI
NKF-ADA Guideline,
UKPDS, ALLHAT
NKF Guideline, Captopril Trial,
RENAAL, IDNT, REIN, AASK
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
21
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
22
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 non-HDLC 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.
23
Lipid Management Recommendations
I IIa IIb III
For all patients
Start dietary therapy (<7% of total calories as saturated
fat and <200 mg/d cholesterol)
I IIa IIb III
Adding plant stanol/sterols (2 gm/day) and viscous
fiber (>10 mg/day) will further lower LDL
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.
24
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.
25
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 LDL-lowering
drug therapy
I IIa IIb III
I IIa IIb III
If on-treatment LDL-C > 100 mg/dL, intensify LDLlowering drug therapy (may require LDL lowering
drug combination)
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.
26
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
I IIa IIb III
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)
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
27
HMG-CoA Reductase Inhibitor: Secondary Prevention
Heart Protection Study (HPS)
20,536 patients with CAD, other occlusive arterial disease, or DM
randomized to simvastatin (40 mg) or placebo for 5.5 years
Event Rate Ratio (95% CI)
Baseline
LDL-C (mg/dL)
Statin
(n = 10,269)
Placebo
(n = 10,267)
<100
282 (16.4%)
358 (21.0%)
100–129
668 (18.9%)
871 (24.7%)
130
1083 (21.6%)
1356 (26.9%)
All patients
2033 (19.8%)
2585 (25.2%)
Statin Better
Statin Worse
0.76 (0.72–0.81)
P<0.0001
0.4
CAD=Coronary artery disease, CI=Confidence interval, DM=Diabetes mellitus,
HPS Collaborative Group. Lancet 2002;360:7-22
0.6
0.8
1.0
1.2
1.4
28
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
29
HMG-CoA Reductase Inhibitor: Secondary Prevention
Relationship between LDL Levels and Event Rates in Secondary Prevention Trials
of Patients with Stable CHD
Statin
30
4S
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
30
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.
31
Physical Activity Recommendations
I IIa IIb III
Goal: 30 minutes 7 days/week,
minimum 5 days/week
Assess risk with a physical activity history and/or an
exercise test, to guide prescription
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
I IIa IIb III
Advise medically supervised programs for high-risk
patients (e.g. recent acute coronary syndrome or
revascularization, HF)
32
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
33
Weight Management Recommendations
Goal: BMI 18.5 to 24.9 kg/m2
Waist Circumference: Men: < 40 inches
Women: < 35 inches
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.
I IIa IIb III
I IIa IIb III
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.
34
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
CV=Cardiovascular
16 20 24 28 32 36
Body Mass Index (kg/m2)*
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
35
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.
36
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
37
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
38
Antiplatelet Agents / Anticoagulation
Recommendations
39
Aspirin Recommendations
I IIa IIb III
I IIa IIb III
I IIa IIb III
Start and continue indefinitely aspirin 75 to
162 mg/d in all patients unless
contraindicated
For patients undergoing CABG, aspirin (100 to
325 mg/d) should be started within 48 hours
after surgery to reduce saphenous vein graft
closure
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
40
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
41
Anticoagulation Recommendations
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.)
I IIa IIb III
Use of warfarin in conjunction with aspirin
and/or clopidogrel is associated with
increased risk of bleeding and should be
monitored closely
42
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
*Aspirin was the predominant antiplatelet agent studied
**Vascular events include MI, stroke, or death
Antithrombotic Trialist Collaboration. BMJ 2002;324:71–86.
0.0
0.5
1.0
1.5
2.0
Antiplatelet better Control better
43
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
44
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 (75-325 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
45
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
46
Renin-Angiotensin-Aldosterone
System Blockers Recommendations
47
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
48
Angiotensin Receptor Blocker
Recommendations
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%.
I IIa IIb III
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
49
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
50
ACE Inhibitor Evidence: Post MI with LVD or HF
AIRE
SAVE
Radionuclide
EF  40%
Probability of Event
TRACE
Clinical and/or
radiographic
signs of HF
Echocardiogram
EF  35%
0.4
0.35
Placebo
0.3
ACE-I
0.25
0.2
0.1
0.15
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
51
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
52
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
Favors Perindopril
1
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
53
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
54
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.
55
ARB Evidence: Post MI with LVD or HF
Valsartan in Acute Myocardial Infarction Trial (VALIANT)
All Cause Mortality
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
Captopril
0.3
Valsartan
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.
56
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
57
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
58
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
59
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
60
b-blocker Recommendations
61
b-blocker Recommendations
I IIa IIb III
Start and continue indefinitely in all post MI, ACS, LV
dysfunction with or without HF symptoms, unless
contraindicated.
I IIa IIb III
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
62
b-blocker Evidence
Summary of Secondary Prevention Trials of b-blocker Therapy
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)
Phase of
Treatment
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.
63
b-blocker Evidence: Post MI with
Left Ventricular Dysfunction
Proportion Event-free
Carvedilol Post-Infarct Survival Control in LV Dysfunction (CAPRICORN)
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.
64
b-blocker Evidence: Benefit in HF and LVSD
Study
Drug
HF
Severity
Patients
(n)
Follow-up
(years)
Mean
Dosage
Effects on Outcomes
CIBIS
Bisoprolol*
ModerateSevere
641
1.9
3.8
mg/day
All cause mortality
22% (p=NS)
CIBIS-II
Bisoprolol*
ModerateSevere
2,647
1.3
7.5
mg/day
All cause mortality
34% (P<0.0001)
BEST
Bucindolol*
ModerateSevere
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
65
Influenza Vaccination
I IIa IIb III
Patients with cardiovascular disease
should have influenza vaccination
66
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.
67
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
68
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.
69
SIMPLE, ONE PAGE, ON-LINE FORM
Demographics
6 clicks
Clinical/Lab
8 clicks
Dischargemeds
and interventions
7 clicks
Interactively
checks
patient’s
data with the
AHA guidelines
70
©2001 Outcome Sciences, Inc.
Impact of AHA Get With The Guidelines-CAD
Program on Quality of Care
* p< 0.05 compared to baseline
* * * Baseline
100
90
80
70
60
50
40
30
20
10
0
97 97
9395 96
83
79
** *
8787
Q1
Q2
91
*
64656567
Aspirin
Q3
68
Beta Blocker ACE Inhibitor
GWTG-CAD: 123 US Hospitals n=27,825
Labresh, Fonarow et al. Circulation 2003;108:IV-722
Q4
*
* * *
* *
737574
70
67
* 82
70
7675
57
Lipid Rx
Smoking
Cessation
71
AHA/ACC 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
72
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.
73