Transcript In-hosptial initiation of CVP meds

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Understanding and Applying
Cardiovascular Treatment
Guidelines
Gregg C. Fonarow, MD, FACC, FAHA
Eliot Corday Professor of CV Medicine and Science
UCLA Division of Cardiology
David Geffen School of Medicine, UCLA
Director, Ahmanson-UCLA Cardiomyopathy Center
Co-Chief, UCLA Division of Cardiology
Los Angeles, California
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Presenter and Program
Disclosure Information
Gregg C. Fonarow, MD
FINANCIAL DISCLOSURE:
Consultant, Honorarium: Medtronic, Novartis
UNLABELED/UNAPPROVED USES DISCLOSURE:
None
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Burden of Atherosclerotic Vascular
Disease: CAD, CVD, PVD
• Prevalence– 25 million in United States
• Annual rates
 Myocardial infarction–1.2 million
 Strokes-795,000
 CVD Mortality–814,000 (every 30 seconds a death)
 Cardiac catheterization–1.1 million
 Percutaneous revascularization–622,00
 Surgical revascularization–232,000
• Annual direct cost–>$280 billion
American Heart Association. 2011 Heart and Stroke Statistical Update. At: http://www.americanheart.org.
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Cardiovascular Disease Remains the
Leading Killer of Men and Women
Deaths per 100,000 Population (log scale)
Death Rates for Leading Causes of Death for All Ages (US, 1950-2002)
1000
Heart disease
Cancer
Stroke
100
Unintentional injuries
Chronic lower
respiratory disease
10
1950
1960
1970
1980
1985
1990
1995
2002
Year
Centers for Disease Control and Prevention. Available at:
http://www.cdc.gov/nchs/ppt/hus/HUS2004Chartbk.ppt#280,25,Slide25. Accessed July 11, 2005.
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Potential Therapies for Atherosclerosis
Folate
Stents
Olive Oil
Calcium Channel Blockers
Nitrates
Iron Chelation
Fish Oils
Phlebotomy
Vitamin B12
Red Wine
Estrogen
Fibrates
Anti-Oxidants
Alcohol
Walnuts
Meditation
Beta Blockers
Niacin
Lasers
Fiber
?
Statins
Garlic
ACE Inhibitors
Weight Loss
Vitamin E
Calcium Chelation
Aspirin
Glucose Control
Coumadin
Exercise
L-Arginine
Soy Beans Platelet antagonists
Acupuncture
Blood Pressure Control
Oat Bran
Vitamin C
Resins
Biofeedback
Beta Carotene
Thyroid Hormones
Vegetables
Gene Therapy
Diet
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AHA/ACCF Secondary Prevention and Risk
Reduction Therapy for Patients With Coronary
and Other Atherosclerotic Vascular Disease:
2011 Update
Sidney C. Smith, JR, MD, FAHA, FACC, Chair; Emelia J. Benjamin, MD, ScM, FAHA,
FACC; Robert O. Bonow, MD, FAHA, FACC; Lynne T. Braun, PhD, ANP, FAHA; Mark A.
Creager, MD, FAHA, FACC; Barry A. Franklin, PhD, FAHA; Raymond J. Gibbons, MD,
FAHA, FACC; Scott M. Grundy, MD, PhD, FAHA; Loren F. Hiratzka, MD, FAHA, FACC;
Daniel W. Jones, MD, FAHA; Donald M. Lloyd-Jones, MD, ScM, FAHA, FACC; Margo
Minissian, ACNP, AACC, FAHA; Lori Mosca, MD, PhD, MPH, FAHA; Eric D. Peterson, MD,
MPH, FAHA, FACC; Ralph L. Sacco, MD, MS, FAHA; John Spertus, MD, MPH, FAHA,
FACC; James H. Stein, MD, FAHA, FACC; Kathryn A. Taubert, PhD, FAHA
J Am Coll Cardiol 2011:58:2432–46
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Secondary Prevention Guidelines
• Since the 2006 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.
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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
Level of
Evidence
A: Multiple randomized controlled trials
B: Single trial, non-randomized studies
C: Expert opinion
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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
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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
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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.
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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
Blood Pressure Control
Recommendations
Goal: <140/90 mm Hg
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
I IIa IIb III
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
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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)
BP=Blood pressure
Prospective Studies Collaboration. Lancet. 2002;360:1903-1913
70 80 90 100 110
Usual Diastolic BP (mm Hg)
Long-Term Antihypertensive Therapy
Significantly Reduces CV Events
Stroke
Myocardial
infarction
Heart failure
0
–10
Average
reduction
in events
(%)
–20
–30
20%-25%
–40
–50
35%-40%
>50%
–60
Blood Pressure Lowering Treatment Trialists’ Collaboration. Lancet. 2000;355:1955-1964.
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JNC VII Lifestyle Modifications for
BP Control
Modification
Recommendation
Approximate SBP
Reduction Range
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
Weight reduction
Adopt DASH
eating plan
BMI=Body mass index, SBP=Systolic blood pressure
Chobanian AV et al. JAMA. 2003;289:2560-2572
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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
Diuretic, BB, ACEI,
ARB, CCB
NKF-ADA Guideline,
UKPDS, ALLHAT
Diabetes Mellitus
Chronic Kidney
Disease
Recurrent Stroke Prevention
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
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Lipid Management Goal
I IIa IIb III
Use statin therapy to achieve LDL-C less than
100 mg/dL
I IIa IIb III
For high risk patients reduction to LDL-C to < 70
mg/dL is reasonable
• If it is not possible to attain LDL-C <70 mg/dL
because of a high baseline LDL-C, it generally is
possible to achieve LDL-C reductions of >50% with
more intensive LDL-C─lowering therapy, including
drug combinations.
If TG >200 mg/dL, non-HDL-C should be < 130 mg/dL*
*Non-HDL-C = total cholesterol minus HDL-C
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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
I IIa IIb III
Promote daily physical activity and weight
management.
Encourage increased consumption of omega-3 fatty
acids in fish or 1 g/day omega-3 fatty acids in capsule
form for risk reduction.
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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)
50%–60% of total calories
Fiber
Protein
Cholesterol
20–30 g/d
~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.
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Impact of Omega-3 Fatty Acid Supplements
in Patients Post Myocardial Infarction
11,324 patients post MI randomized to Omega-3 FA supplements 1g/d vs placebo
Lancet 1999; 354: 447-55
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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
If on-treatment LDL-C > 100 mg/dL, intensify LDLlowering 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.
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Simvastatin Reduced the Risk of Major Coronary Events
Subgroup Analyses From The Simvastatin Survival Study
0
Percent Risk Reduction
-10
-20
-30
-31
-34
-40
P<0.00001
n=1814
-35
-34
P=0.01
n=407
P<0.0005
n=1156
P<0.002
n=542
-50
-37
P<0.002
n=573
-55
-60
P=0.002
n=105
-70
Men
4S Study
Women
Lancet 1994;344:1383
Older
Smokers
Hypertension
Diabetes
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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
CAD=Coronary artery disease, CI=Confidence interval, DM=Diabetes mellitus,
HPS Collaborative Group. Lancet 2002;360:7-22
1.0
1.2
1.4
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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
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TNT: Primary Efficacy Outcome Measure
First Major Cardiovascular Event*
Proportion of patients experiencing
major cardiovascular event
0.15
HR = 0.78 (95% CI 0.69, 0.89)
P=0.0002
Relative
risk
reduction
= 22%
Atorvastatin 10 mg
0.10
Atorvastatin 80 mg
0.05
0
0
1
2
3
Time (years)
4
5
* CHD death, nonfatal non-procedure-related MI, resuscitated cardiac arrest, fatal or nonfatal stroke
LaRosa et al. N Engl J Med 2005:352 online
6
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HMG-CoA Reductase Inhibitor:
Secondary Prevention
Relationship between LDL Levels and Event Rates in
Secondary Prevention Trials of Patients with Stable CHD
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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
AIM-HIGH Primary Outcome
Cumulative % with Primary Outcome
50
Statin- Niacin ER Combination Therapy
Statin Monotherapy
40
30
HR 1.02, 95% CI 0.87, 1,21
Log-rank P value= 0.79
20
16.4%
16.2%
10
0
0
1
Combination Therapy
3
4
Time (years)
N at risk
Monotherapy
2
1696
1581
1381
910
436
1718
1606
1366
903
428
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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
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)
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Exercise Evidence: Mortality Risk
Observational study of self-reported physical activity in 772 men with established
coronary heart disease
Wannamethee SG et al. Circulation 2000;102:1358-1363
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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.
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CV Risk Increases with Body Mass
Index
Hazard Ratio
Hemorrhagic
Stroke
Ischemic
Stroke
Ischemic Heart
Disease
4.0
4.0
4.0
2.0
2.0
2.0
1.0
1.0
1.0
0.5
0.5
0.5
16 20 24 28 32 36
16 20 24 28 32 36
Body Mass Index (kg/m2)*
CV=Cardiovascular
Body mass index is calculated as the weight in
kilograms divided by the body surface area in meters2.
Mhurchu N et al. Int J Epidemiol 2004;33:751-758
16 20 24 28 32 36
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Relative Risk of
Cardiovascular
Disease Mortality
Overweight and Obesity Increase the
Risk of Cardiovascular Disease Mortality
and All-Cause Mortality
CVD mortality
3.0
Men
Women
2.6
2.2
1.8
1.4
1.0
0.6
Normal weight
Overweight
>18
25
Obese
30
>40
Relative Risk of
All- Cause Mortality
BMI (kg/m2)
All-cause mortality
Men
Women
3.0
2.6
2.2
1.8
1.4
1.0
0.6
Normal weight
Overweight
>18
25
Obese
30
>40
BMI (kg/m2)
Data are from 1 million men and women followed for 16 years with an average age of 57 who never
smoked and had no history of disease at enrollment.
Calle et al. N Engl J Med. 1999;341:1097-1105.
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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
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Diabetes Mellitus Recommendations
I IIa IIb III
I IIa IIb III
I IIa IIb III
Lifestyle modifications including daily physical
activity, weight management, blood pressure
control, and lipid management are recommended
for all patients with diabetes.
Coordinate diabetic care with patient’s primary
care physician or endocrinologist.
A target HbA1c of ≤7% may be considered
HbA1c = Glycosylated hemoglobin
36
Primary Composite Endpoint* (%)
Intensive Multiple Risk Factor Management Patients
with Type 2 Diabetes: STENO-2
60
N=160; follow-up=7.8 years
Conventional Therapy
40
20% Absolute
Risk Reduction
20
Aggressive treatment of†:
– Microalbuminuria with
ACEIs, ARBs, or combination
– Hypertension
– Hyperglycemia
– Dyslipidemia
– Secondary prevention of CVD
Intensive Therapy†
12
24
36
48
60
72
84
96
Months of Follow-Up
Primary composite endpoint: conventional therapy (44%) and intensive therapy (24%).
*Death from CV causes, nonfatal MI, CABG, PCI, nonfatal stroke, amputation, or surgery for peripheral atherosclerotic
artery disease. †Behavior modification and pharmacologic therapy.
Adapted from Gaede P, et al. N Eng J Med. 2003;348:383-393.
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Antiplatelet Agents / Anticoagulation
Recommendations
38
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
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.
39
40
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
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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,
>12 months for sirolimus-eluting stent
>12 months for paclitaxel-eluting stent
*Clopidogrel is generally given preference over Ticlopidine because of a superior safety profile
42
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
Months of Follow Up
NSTEMI-ACS=Non ST-segment elevation acute coronary syndrome
The CURE Trial Investigators. NEJM. 2001;345:494-502
9
12
43
CHARISMA: Primary Efficacy
Outcome (MI, Stroke, or CV Death)†
Cumulative event rate (%)
8
Placebo + ASA*
7.3%
6
Clopidogrel + ASA*
6.8%
4
RRR: 7.1% [95% CI: -4.5%, 17.5%]
P = 0.22
2
0
0
6
12
18
24
Months since randomization§
†
30
First Occurrence of MI (fatal or non-fatal), stroke (fatal or non-fatal), or cardiovascular death
*All patients received ASA 75-162 mg/day
§The number of patients followed beyond 30 months decreases rapidly to zero and there are
only 21 primary efficacy events that occurred beyond this time (13 clopidogrel and 8 placebo)
Adapted with permission from Bhatt DL, et al. N Engl J Med. 2006;354.
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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
45
Renin-Angiotensin-Aldosterone System
Blockers Recommendations
46
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
47
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
48
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
49
ACEI Therapy in Patients with Atherosclerosis
Relative Risk of Mortality
Clinical Trial
N
Deaths
HOPE
9,297
1051
HR 0.84 P=0.005
EUROPA
12,218
795
HR 0.89 P=0.10
PEACE
8,290
All Trials
33,960
633
HR 0.89 P=0.13
HR 0.86 P<0.001
>3000
0.4
0.6
0.8 1.0
ACEI Better
1.2
1.4
1.6
Placebo Better
7 RCT, 33,960 randomized, 4.4 year follow-up, CVD HR 0.81, MI HR 0.82, Stroke HR 0.77
Danchin et al Arch Intern Med 2006;166:787-796
50
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
51
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.
52
ARB Evidence: Stable CAD or Diabetes
Telmisartan, Ramipril, or Both in Patients at High Risk for Vascular Events
8576 assigned to receive 10 mg of ramipril per day, 8542 assigned to receive
80 mg of telmisartan per day, and 8502 assigned to receive both drugs
0.20
0.15
Cumulative
hazard ratio
N = 25,620 with vascular
disease or high-risk diabetes
0.10
0.05
0.00
0
1
2
3
4
5
Follow-up (years)
Telmisartan
Ramipril
OnTarget Investigators NEJM 2008;358:1547-1559.
Telmisartan plus ramipril
53
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
54
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
55
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
Month
EF=Ejection fraction, LVSD=Left ventricular systolic dysfunction, MI=Myocardial infarction
Pitt B et al. NEJM 2003;348:1309-21
36
Eplerenone in Patients with Systolic HF
and Mild Symptoms: EMPHASIS HF
Primary Endpoint: CV Mortality and HF Hospitalization
50
Primary Endpoint:
Cumulative K-M Rate (%)
HR = 0.63 (0.54-0.74), p <0.001
40
Placebo
356 (25.9%)
Eplerenone
249 (18.3%)
30
20
10
0
0
No. at Risk
Placebo
Eplerenone
1373
1364
1
2
Years from Randomization
848
925
Zannad F. New Engl J Med. 2011;364:11-21.
512
562
3
199
232
57
b-blocker Recommendations
58
b-blocker Recommendations
I IIa IIb III
Beta-blocker therapy should be used in all patients with
left ventricular systolic dysfunction (ejection fraction
40%) with heart failure or prior myocardial infarction,
unless contraindicated. (Use should be limited to
carvedilol, metoprolol succinate, or bisoprolol, which
have been shown to reduce mortality.)
I IIa IIb III
Beta-blocker therapy should be started and continued for
3 years in all patients with normal left ventricular
function who have had myocardial infarction or ACS
I IIa IIb III
Consider chronic therapy for all other patients with
coronary or other vascular disease or diabetes unless
contraindicated.
MI=Myocardial infarction, HF=Heart Failure
59
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.
b-blocker Evidence: Post MI with
60
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
Years
The CAPRICORN Investigators. Lancet. 2001;357:1385–1390.
Placebo
2
2.5
61
b-blocker Evidence: Benefit in HF and LVSD
US Carvedilol Study*1
CIBIS II2
1.0
Carvedilol
(n=696)
0.8
Placebo
(n=398)
Survival
Survival
1.0
Risk Reduction=65%
P<.001
0.6
Bisoprolol
(n=1327)
0.8
Risk Reduction=34%
P<.0001
0.6
0
0
0
3
6
9
0
12
3
MERIT-HF3
1.0
6
9
12 15 18 21 24
Time After Inclusion (months)
Months
1.0
COPERNICUS4
Metoprolol CR/XL
(n=1990)
0.8
Placebo
(n=2001)
0
0
1Packer
3
6
9 12 15 18
Months of Follow-up
0.8
P=.0014
0
21
Placebo
(n=1133)
Risk Reduction=35%
0.6
Risk Reduction=34%
P=.0062
0.6
Carvedilol
(n=1156)
Survival
Survival
Placebo
(n=1320)
0
3
6
9
12
15
18
21
Months
M et al. N Engl J Med. 1996;334:1349-1355. 2CIBIS II Investigators and Committees. Lancet. 1999;353:9-13.
3MERIT-HF Study Group. Lancet. 1999;353:2001-2007.
62
Influenza Vaccination
I IIa IIb III
Patients with cardiovascular disease should have
influenza vaccination
63
Influenza Vaccination Evidence
Effectiveness of Influenza Vaccination during the Influenza Seasons
Hospitalization
Vaccinated
Unvaccinated
Subjects
Subjects
(N=77,738)
(N=62,317)
495 (0.6)
581 (0.9)
Adjusted Odds
Ratio
P value
0.68
Pneumonia or influenza
<0.001
(0.60–0.78)
0.81
Cardiac disease
888 (1.1)
1026 (1.6)
<0.001
(0.73–0.89)
0.80
Ischemic heart disease
457 (0.6)
535 (0.9)
0.001
(0.70–0.91)
0.81
Heart failure
466 (0.6)
538 (0.9)
0.002
(0.70–0.92)
0.84
Cerebrovascular disease
398 (0.5)
427 (0.7)
0.018
(0.72–0.97)
0.52
Death
943 (1.2)
1361 (2.2)
<0.001
(0.47–0.57)
0.65
Hospitalization or death
2387 (3.1)
2910 (4.7)
<0.001
(0.62–0.70)
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.
64
Therapies Not Recommendations
65
Impact of Vitamin E Supplementation in Men
and Women Post Myocardial Infarction
GISSI Prevention
100
% Surviving (free of MI, stroke, death)
n=5660
95
n=5664
90
Vitamin E
Placebo
85
RR 0.95 (0.86-1.05)
P=0.293
80
75
70
0
6
12
18
24
30
36
42
Months
11,324 patients post MI randomized to Vitamin E 300 mg/d vs placebo
1700 women, ave age 59 92% asa, 44% bb, 50% acei, 20% statin
Lancet 1999; 354: 447-55
48
66
Hormone Replacement as a Therapeutic
Agent in Cardiovascular Disease
RH 1.24 (0.87-1.75)
2763 Postmenopausal women with CAD: 0.625 Equine Estrogen and 2.5 mg MPA v s Placebo
14% reduction in LDL and 8% increase in HDL
HERS Research Group Hulley JAMA:280:605-613
67
Homocysteine Lowering with Folic Acid
and B Vitamins in Vascular Disease
HOPE 2 N Engl J Med 2006;354:1567-1577
Bonna N Engl J Med 2006;354:1578-1588
68
Atherosclerosis as the Therapeutic Target
Therapies with Demonstrated Benefit



Anti-Platelet Therapy
Aspirin and/or Clopidigrel
Neurohumoral Inhibition
Beta Blockers
ACE Inhibitors
Lipoproteins / Inflammation
Statins (irrespective of baseline LDL)
Omega-3 Fatty Acids
Exercise
Smoking Cessation
69
Conceptual Basis for Combination Cardiovascular
Protective Medical Therapy for Atherosclerosis
Hypertension
Apo B100
Lp (a)
Triglycerides
CRP Activated monocytes
Angiotensin II
Aldosterone
Serum amyloid IL-6
Obesity
M-CSF
ECAM
ICAM
Oxidized LDL
Fibrinogen
P-selectin
AGEs
Chylomicron Remnants
Diabetes
Epinephrine
Endothelin
Tissue Factor
NAPDH oxidases
Norepinephrine
Superoxide anion
Iron
TNF
CD-40 ligand
Particulate matter
Insulin
Xanthine oxidase
PAI-1
Myeloperoxidase
Uric acid
Smoking
Aponectin
Homocysteine
Chlamydia
Apo E
PDGF
Age
Small dense LDL
ADMA
70
Interaction Between Therapies to Treat Atherosclerosis
28.9
Placebo Only
18.6
Statin Only
11.2
Statin+ASA
8.6
70% Reduction
Statin+ASA+BB
0
5
10
15
20
25
30
35
Coronary Event Rate (%)
Treatment in 4S 4444 Patients with CAD Only statin vs placebo randomized 5.4 years F/U
Placebo 24% Statin 24% Statin+ASA 8% Statin+ASA+Beta Blocker 18%
71
Statin Therapy is Additive to Other Cardioprotective
Therapies in Patients with Atherosclerosis or Diabetes
Background Therapy
Relative Risk of CV Event
N
Aspirin +
Aspirin -
12984
7552
Beta Blocker +
Beta Blocker -
5279
15257
ACE Inhibitor +
ACE Inhibitor -
3979
16557
0.4
0.6
0.8 1.0
Simvastatin Better
1.2
1.4
1.6
Placebo Better
P=NS
Heart Protection Study Lancet 2002;360:7-22.
Test for heterogeneity
72
ACEI Therapy is Additive to Other Cardioprotective
Therapies in Patients with Atherosclerosis or Diabetes
Background Therapy
Relative Risk of CV Event
N
Aspirin +
Aspirin -
6813
2484
Beta Blocker +
Beta Blocker -
3673
5624
Lipid Lowering +
Lipid Lowering -
2658
6639
0.4
0.6
0.8 1.0
Ramipril Better
1.2
1.4
1.6
Placebo Better
P=NS
Dagenais Circulation 2001;104:522-526.
Test for heterogeneity
73
Cumulative Impact of Simple
Cardiovascular Protective Medications
Relative-risk
2 yr CV event rate
None
--
20%
Aspirin
25%
15%
Beta blocker
25%
11.3%
ACE inhibitor
25%
8.4%
Lipid lowering Rx
30%
5.9%
LDL 100
16%
5.0%
70 mg/dl
Cumulative risk reduction if all four therapies are used: 75%
Absolute risk reduction: 15%, NNT = 6
CV event = CV death, MI, or stroke
Fonarow Am J Cardiol 2001;85:10A-17A and Yusuf Lancet 2002;360:2-3
74
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
Making Sure All Patients Get Indicated
Therapy: The UCLA CHAMP Program
75
Patient with coronary, cerebral, or peripheral atherosclerosis
(documented by clinical, ultrasound, stress test or angiographic criteria)
Obtain admission lipid panel, liver function tests
Hospital Phase
of Care
Start :
• Aspirin, clopidogrel or both
• Beta blocker
• ACE inhibitor
• Statin
• Exercise, omega 3FA, and dietary counseling
Obtain lipid panel, liver function tests
Outpatient
Phase of Care
LDL > 70 mg/dL
LDL < 70 mg/dL
Advance statin dose
and/or combination rx
Continue treatment
Reinforce compliance
Recheck in 3-6 months
Continue treatment
Recheck in 6 weeks
76
Implementation of CHAMP
Focused Treatment
Guidelines
and Algorithm
Preprinted
Admit
Order Sheets
Discharge Forms
and Outpt
F/U Process
Patient
Education
Materials
CHAMP tool kit: www.med.ucla.edu/champ
Fonarow GC et al. Am J Cardiol 2000;85:10A-17A.
Focused Lectures
by Opinion
Leaders
Measurement
and Utilization
Reports
77
Proof of Concept: CHAMP
CAD Patient Treatment Rates
Pre-CHAMP
Hospital discharge:
Aspirin
Beta-Blocker
ACEI
Statin
12-month follow-up:
Statin
LDL < 100 mg/dL
Fonarow Am J Cardiol 2001;87:819-822
Post-CHAMP
‘92-’93
‘94-’95
(n=256)
(n=302)
78%
12%
4%
6%
92%*
61%*
56%*
86%*
10%
6%
91%*
58%*
78
CHAMP: Sustained Impact
Over a 10-Year Period
Comparison of UCLA (1992–2003) to NRMI IV (2002/2003) National Rx Rates
92/93
100
90
80
70
60
50
40
30
20
10
0
92 91 94 92
94/95
96
96/97
92
68
68
72
78
00/01
82
64
02/03
88 89 90 91
88 90
85
85
98/99
92
70
52
58
52
12
6
4
ASA
Beta-Blocker
ACEI
Statin
National Registry of Myocardial Infarction Discharge Medications at UCLA compared with 1283 NRMI hospitals.
Revised from Fonarow GC et al. Circulation. 2001;104:II-711.
79
CHAMP Study: Clinical Events for the First Year
After Discharge for Acute MI
15
14.8
* P < .05
Pre-CHAMP
Post-CHAMP
10
7.6*
7.8
5
7.0
4.7
3.3*
3.1*
2.6
0
Recurrent
MI
Heart
Failure
Fonarow GC, et al. Am J Cardiol. 2001;87:819-822.
Hospitalization
Total
Mortality
80
Why a Hospital-based System for
ACS and Heart Failure Management?
• Patients
– Patient capture point
– Have patient’s/family’s attention:
“teachable moment”
– Predictor of care in community
• Hospital structure
– Standardized processes/protocols/
orders/teams
– Accrediting bodies for standards of care
– Centers for Medicare and Medicaid
Services (CMS) and peer review organizations
• JCAHO (in-hospital)
• HEDIS (post-discharge)
81
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.
82
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
©2001 Outcome Sciences, Inc.
83
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
84
GWTG Associated with Improved Treatment at
Teaching and Non-Teaching Hospitals
Baseline
100
90
80
70
60
50
40
30
20
10
0
Q1
*
85
*
56
68 *
62
Q3
Q4
*
*
* 85
* 81
76
67 67
*
* 88
88
*
75 77
*
*
Q2
* 86
* 79
75
72
58
62
43
Teaching
Non-Teaching
Smoking Cessation
GWTG-CAD: 123 US Hospitals n=27,825
Fonarow et al. Circulation 2003;108:IV-721
Teaching
Non-Teaching
Cardiac Rehab/Exercise
* p< 0.05 compared to baseline
85
Results with GWTG-HF:
Performance Measures
Baseline
P=0.127
100
90
80
70
60
50
40
30
20
10
0
p<0.0001
70
74 74 75
Q1
Q2
83 81 83 82
DC Instructions
Q4
P=0.046
P=0.036
91 92 92 92 91
79
Q3
85
87 87 86
84
p<0.0001
90
89
81 82 81
74
LVF Measurement
ACEI/ARB
Beta Blocker
Data from 97 GWTG-HF hospitals and 18,516 HF patients were collected from 1/05-3/06
Fonarow GC et al. Submitted HFSA 2006
Smoking
Cessation
86
The Science of Implementation
It is possible to create a hospital based
system to implement atherosclerosis treatment
In-hospital treatment rates are markedly improved
It is safe to initiate lipid-lowering and other
cardioprotective medications in the hospital
In-hospital initiated treatments are continued by
outpatient physicians
In-hospital initiation of treatments markedly improves
long term patient compliance
In-hospital initiation of lipid lowering therapy results in
more patients reaching a LDL < 100 mg/dl
It reduces total medical costs
In-hospital initiation of cardioprotective therapies
reduces recurrent CV events and saves lives
87
Key Elements to Quality Improvement:
Why Do Some Programs Succeed?
• Access to current and accurate data on
treatment and outcomes
• Have stated goals
• Administrative support
• Support among clinicians
• Use of care maps and pathways
• Use of data to provide feedback
Bradley EH, et al. JAMA. 2001;285:2604-2611.
89
Secondary Prevention:
Medications
Goals
• Aspirin
• BP <140/90 mm Hg (<130/80
mm Hg with diabetes or CKD)
• Clopidogrel
• β-blockers
• ACE inhibitors/ARBs
• Aldosterone blockade (Low EF)
• Lipids
- Fasting lipid panel within 24 h
of hospitalization
– Statins before discharge
– Goal LDL-C <100 mg/dL
– LDL <70 mg/dL is reasonable
Anderson JL, et al. J Am Coll Cardiol. 2007;50:652-726.
King SB 3rd, et al. J Am Coll Cardiol. 2008;51:172-209.
• Smoking cessation/no
environmental smoke
exposure
• Physical activity (30 min,
7 d/wk; min 5 d/wk)
• Weight management
• Diabetes management: HbA1c
<7%
• Annual influenza
immunization
90
Conclusions
• Comprehensive application of secondary
prevention therapies is highly effective in
reducing the risk of cardiovascular events
• Despite the clinical trial evidence and national
guidelines, large number of eligible patients are
not receiving one or more of these
recommended therapies
• As such, large number of patients are having CV
events that could be avoided if there was better
implementation
• Every effort should be made to bridge the
cardiovascular risk reduction gap