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Preventing Cardiovascular
Events
Primary and Secondary
November 8th 2014
Slides by Dr Dharmesh Patel and Arie Szatkowski
Last Minute Presentation by Dr Arie Szatkowski
NBC’s Tim Russert dies at 58
• Russert was recording voiceovers
when he collapsed.
• Previously diagnosed with
asymptomatic coronary artery
disease.
Dr. Michael Newman (Russert’s physician) said his
disease was “well-controlled with medication and
exercise, and he had performed well on a stress test.”
Cardiac Stress Tests
Limitations:
• Requires a high level of blockage
in one or more coronary arteries
for abnormal result.
• Most heart attacks occur in vessels
without significant blockage, or
stenosis.
What is the solution? Or, is there any?
When asked if he thought he could
have done more, Dr. Newman
replied…
“You know, as physicians, we always
hope that we can change people's lives,
that we can make them feel better, live
longer, that we can intervene, and that's
what our role is. Unfortunately, in many
instances, our hopes are not fulfilled.
Absolutely, I wish Tim was alive and
with us today. ... And ... patients die of
heart disease or cancer; we
all
struggle with the fact there
are limits to what we can
do.”
Dr. Newman on
The Larry King Show
Definitions of Different Types of
Prevention
• Primordial Prevention: Prevention of coronary
heart disease risk factors
• Primary Prevention: Modification of risk factors
in order to prevent or delay the onset of
coronary heart disease
• Secondary Prevention: Initiation of therapy to
reduce recurrent coronary heart disease events
and decrease cardiac mortality in patients with
established coronary heart disease.
Advances in CVD Risk Reduction
Not Enough
• CVD is the leading cause of
death in the United States,
despite guideline driven care.1
• CVD accounts for 33% of
all deaths.2
• Total CVD healthcare costs are
projected to rise from $313
billion in 2009 to $1.48 trillion in
2030.2
• 50% of people who have had
a heart attack have normal
cholesterol.3
1. Roger et al. Circulation. 2011;123(4):e18-e209.
2. Go AS, Mozaffarian D, Roger VL, et al. Circulation. 2013;127:e2-e245.
3. Sachdeva et al. Am Heart J. 2009;157(1):111-117.e2.
7
© 2014 Boston Heart Diagnostics Corporation
Major Risk Factors for
Cardiovascular Disease
• Smoking – 1964 – 1st Surgeon General ‘s report linking smoking with
heart disease, lung cancer, and emphysema– marked decrease
• Diet – 1968 – The US food industry replaces lard and tallow in many
foods with vegetable oil – beneficial effects on LDL-C and CHD risk.
• High Blood Pressure - 1972 – National High Blood Pressure Education
Program and Treatment Guidelines - blood pressure control (JNC 7, get
systolic < 130 mmHg, major reduction in CVD, especially stroke)
• Cholesterol - 1988 – National Cholesterol Education Program Adult
Treatment Panel Guidelines (latest 2004) – get LDL-C < 100, CVD < 70
• Diabetes - 1993 – Diabetes Control and Complication Trial – 2013
guidelines for the diagnosis and treatment of diabetes – get HbAIc < 7%.
• Age Adjusted CVD Rates – have dropped by > 50% since 1964
• Emerging Targets – sdLDL, HDL Particles, Lipoprotein(a), and CRP
Smoking and Heart Disease
•
•
•
•
•
•
Single most preventable cause of
death in the U.S
Causes plaque to form in blood
vessels
Reduces HDL (“good”) cholesterol
May cause irregular heart rhythms
that could lead to cardiac arrest
Puts women who smoke at a much
higher risk of developing
cardiovascular disease
Good News: quitting begins to
reduce cardiovascular risk
immediately
Obesity Trends* Among U.S. Adults
BRFSS, 1990, 2000, 2010
(*BMI 30, or about 30 lbs. overweight for 5’4” person)
2000
1990
2010
No Data
<10%
10%–14%
15%–19%
20%–24%
25%–29%
≥30%
Obesity in Mississippi
• 2nd Fattest state in the country
• Over 2/3 of MS adults are overweight
• Over 26% are obese
• Only 38 % get recommended physical activity
• # 1 in heart disease deaths
• # 1 in young adults with diabetes
• Annual state costs at least $757 million with
overweight and obesity
Scope of the Problem (Cont’d)
Prevalence of CHD associated with 3 projections of adult obesity
Population prevalence of CHD
Prevalence (%)
Number of Excess Cases
Excess prevalence of CHD
Year
Year
Extrapolation from current data suggests that overweight adolescents will
increase rates of CHD among future young and middle-aged adults
CHD=Coronary heart disease
Source: Bibbins-Domingo K et al. NEJM 2007;357:2371-2379
2013 American Heart Association/
American College of Cardiology Guidelines
• “dietary pattern that emphasizes fruits and
vegetables, whole grains, legumes, fish, poultry,
nuts and vegetable oils for fat, and restricted
consumption of saturated and trans fats, sugar,
sodium, and red meat”.
• Dietary pattern evocative of the Mediterranean or
DASH-type diet
J. Am. Coll. Cardiol. 2014 Jan. 28
Mediterranean Diet Study
• 7447 men and women in Spain at high CVD risk (age 55-80 years)
received either: 1) Mediterranean diet with extra-virgin olive oil (140
ml/day), 2) Mediterranean diet with mixed nuts (30 grams/day of
walnuts, almonds, and hazelnuts), or 3) a control diet (advice to
reduce dietary fat).
• Adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54
to 0.92) for M diet group with olive oil and 0.72 (95% CI, 0.54 to 0.96)
for the M diet group with nuts, respectively, versus the control group.
No diet-related adverse effects were reported.
• Primary end point was the rate of major cardiovascular events
(myocardial infarction, stroke, or CVD death)
• Conclusions: “ Among persons at high cardiovascular risk,
a Mediterranean diet supplemented with extra-virgin olive oil or nuts
reduced the incidence of major cardiovascular events.”
Estruch R et al N Engl J Med. 2013 Apr 4;368(14):1279-90.
Associations Between the Percent of
Calories Derived from Specific Foods and
CHD Mortality in the 20 Countries Study*
Food Source
Correlation Coefficient†
Butter
0.546
All dairy products
0.619
Eggs
0.592
Meats
0.561
Sugar and syrup
0.676
Grains, fruits, and vegetables
-0.633
*1973 data, all subjects. From Stamler J: Population studies. In Levy R: Nutrition, Lipids, and CHD. New
York, Raven, 1979. †All coefficients are significant at the P<0.05 level.
Dietary Recommendations
Primary Prevention
I IIa IIb III
Women should consume a diet rich in fruits and
vegetables; choose whole-grain, high-fiber foods; consume
fish, especially oily fish,* at least twice a week; limit
intake of saturated fat to <10% of energy, and if possible to
<7%, cholesterol to <300 mg/d, alcohol intake to no more
than 1 drink per day, and sodium intake to <2.3 g/d
(approximately 1 tsp salt). Consumption of trans-fatty acids
should be as low as possible (eg, <1% of energy)
*Pregnant and lactating women should avoid eating fish potentially high in methylmercury
Source: Mosca L et al. Circulation 2007;115:1481-1501
2013 AHA/ACC Guideline on Lifestyle
• For blood pressure lowering, if recommended goals
for sodium are not attainable, reducing sodium
intake by at least 1,000 mg/day lowers blood
pressure.
• A reduction in sodium intake of approximately 1,000
mg/day reduces CVD events by approximately 30%.
• Combining the DASH dietary pattern with lower
sodium intake is recommended for lowering blood
pressure.
Exercise Reduces Cardiac Event Recurrence
Steffen-Batey et al. Change in level of physical activity and risk of all-cause mortality or
reinfarction: The Corpus Christi Heart Project. Circulation. 102(18):2204-9, 2000 Oct 31.
Physical Activity: Secondary Prevention
Age-adjusted mortality
rate/1000 person-years
Observational study of self-reported physical activity in 772 men with CHD
Physical activity
Moderate exercise is associated with reduced mortality
CHD=Coronary heart disease, CVD=Cardiovascular disease
Source: Wannamethee SG et al. Circulation 2000;102:1358-1363
CV Benefits of Lowering BP
Average Percent Reduction
• Stroke incidence
35–40%
• Myocardial infarction
20–25%
• Heart failure
50%
2014 Evidence-Based Guideline for the Management of High
Blood Pressure in Adults
Report From the Panel Members Appointed to the Eighth Joint
National Committee (JNC 8)
Condition
mmHg
Primary hypertension
<140/90
Diabetes mellitus
<140/90*
Chronic renal disease
<140/90*
Age > 60 years
<150/90*
JAMA.Published online December 18, 2013.
JNC VIII Guidelines
•
For younger patients (age, <60), drug therapy should be considered for
diastolic BP ≥90 mm Hg or systolic BP ≥140 mm Hg. The goal is <140/90 mm
Hg, but only the diastolic thresholds are based on high-quality evidence.
•
In the general population <60 years, initiate pharmacologic treatment to lower
BP at DBP 90mmHg and treat to a goal DBP<90mmHg
•
In the general population aged 60 years, if pharmacologic treatment for high BP
results in lower achieved SBP (eg, <140mmHg) and treatment is well tolerated
and without adverse effects on health or quality of life, treatment does not need
to be adjusted.
•
For older patients (age, ≥60), drug therapy should be considered for diastolic
BP ≥90 mm Hg or systolic BP ≥150 mm Hg; the goal is <150/90 mm Hg.
•
For patients with diabetes and patients with chronic kidney disease, the
threshold to initiate drug therapy is 140/90 mm Hg; the goal is <140/90 mm Hg.
JNC VIII Guidelines Cont’d
• In nonblack patients, acceptable initial drug-class choices are
thiazide-type diuretics, calcium-channel blockers (CCBs),
angiotensin-converting–enzyme (ACE) inhibitors, and angiotensinreceptor blocker (ARBs).
• In black patients, acceptable initial drug-class choices are thiazidetype diuretics or CCBs.
• Patients with chronic kidney disease generally should receive ACE
inhibitors or ARBs.
• When patients require escalation of therapy, either maximizing doses
of individual drugs sequentially or combining several drugs at
submaximal doses is acceptable. Do not use ACE inhibitors and
ARBs together.
Changes compared to JNC VII
Guidelines
•
JNC 7 recommended a treatment threshold of 140/90 mm Hg regardless
of age, whereas JNC 8 raises the systolic threshold at age 60.
•
In addition, JNC 7 recommended a lower treatment threshold (130/80 mm
Hg) for patients with diabetes or chronic kidney disease, but JNC 8 does
not.
•
In JNC 7, thiazide-type diuretics were recommended as initial drug
therapy (unless compelling reasons dictated another drug class), with
CCBs, ACE inhibitors, ARBs, and β-blockers as alternates. In JNC 8, the
initial drug choice is broadened to four classes for nonblack patients and
two classes for black patients.
•
β-blockers are no longer recommended for initial therapy because they
might afford less protection against stroke.
On-Treatment LDL-C is Closely Related to CHD Events
in Statin Trials – Lower is Better
30
4S - Placebo
25
Rx - Statin therapy
PRA – pravastatin
ATV - atorvastatin
20
Secondary Prevention
4S - Rx
LIPID - Placebo
15
10
5
TNT – ATV80
PROVE-IT – ATV
LIPID - Rx
CARE - Rx
HPS - Rx
TNT – ATV10
PROVE-IT - PRA
0
60
(1.6)
Primary Prevention
HPS - Placebo
WOSCOPS – Placebo
AFCAPS - Placebo
But, how low should we
go?
40
(1.0)
CARE - Placebo
80
(2.1)
AFCAPS - Rx
6
WOSCOPS - Rx
ASCOT - Placebo
ASCOT - Rx
100
(2.6)
120
(3.1)
LDL-C achieved mg/dL (mmol/L)
140
(3.6)
160
(4.1)
Adapted from Rosensen RS. Exp Opin Emerg Drugs 2004;9(2):269-279
LaRosa JC et al. N Engl J Med 2005;352:e-version
180
(4.7)
200
(5.2)
Majority of Residual Risk for
Cardiovascular Events Remains Despite
LDL Lowering Therapy
Reduction in Major
Coronary Events (%)
0
100
[-20]
-38%
-25%
-25%
-27%
-31%
-38%
62%
75%
75%
73%
69%
62%
4S
LIPID
CARE
HPS
WOSCOPS
AFCAPS/TexCAPS
4,444
9,014
4,159
20,536
6,595
6,605
80
[-40]
60
Residual Major
Coronary Events (%)
[-60]
40
[-80]
20
[-100]
0
Trial
N
Secondary Prevention
High Risk
Primary Prevention
Adapted from Libby P. The forgotten majority: unfinished business in cardiovascular risk reduction. J Am Coll Cardiol. 2005;46(7):1225-1228.
26
© 2014 Boston Heart Diagnostics Corporation
Groups Recommended for Statin Therapy
•
Group 1: Subject with evidence of clinical CVD (acute coronary
syndrome, history of myocardial infarction, stable or unstable angina,
coronary or other revascularization, stroke, transient ischemic attacks,
and/or peripheral vascular disease. (should receive high intensity statin
and ideally get more 50% LDL-C reduction)
•
Group 2: Subject with LDL-C > 190 mg/dL. (should receive high intensity
statin)
•
Group 3: Diabetic subject age 40 - 75 years with LDL-C of 70 - 189 mg/dL
and without CVD. (should receive moderate intensity statin, and get 30 50% LDL-C reduction)
•
Group 4: Subject without ASCVD or diabetes and a 10 year ASCVD risk
>7.5% (should receive low intensity statin). Use the risk calculator at
www.myamericanheart.org/cvrisk calculator (gender, age, sys. Bp,
smoking, diabetes, total cholesterol, and HDL cholesterol)
Goff DC Jr et al. 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk: A Report of the
American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation.
2013 Nov 12.
Definitions of Statin Intensity
• High: atorvastatin 40 - 80 mg/day, rosuvastatin 20 40 mg/day;
• Moderate: atorvastatin 10 - 20 mg/day, rosuvastatin
5 - 10 mg/day, simvastatin 20 - 40 mg/day,
pravastatin 40 mg/day, lovastatin 40 mg/day,
fluvastatin XL 80 mg/day, or pitavastatin 2 - 4
mg/day;
• Low: simvastatin 10 mg/day, pravastatin 10 - 20
mg/day, lovastatin 20 mg/day, fluvastatin XL 20 - 40
mg/day, or pitavastatin 1 mg/day.
Stone NJ et al. 2013 ACC/AHA Guideline on the Treatment of Blood
Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report
of the American College of Cardiology/American Heart Association Task Force
on Practice Guidelines. Circulation. 2013 Nov 12.
Use of Non-Statin Agents
•
“Clinicians treating high risk patients who have a less
than anticipated responses to statins, who are unable
to tolerate a less than recommended intensity of a
statin, or who are completely statin intolerant, may
consider the addition of a nonstatin cholesterol
lowering drug.“
• “Clinicians should preferentially prescribe drugs that
have been shown in randomized clinical trials to
provide ASCVD risk reduction benefits that outweigh
the potential for adverse effects and drug-drug
interactions. Fibrates, niacin, resins, and the
statin/ezetimibe combination have shown ASCVD risk
reduction in randomized trials as compared to
placebo.”
AIM HIGH-Post HOC Analysis
 In 3-year follow-up in 3,414 patients with CVD and HDL-C < 40
mg/dL combined niacin + LDL-C lowering therapy did not reduce
CV events compared with LDL-C-lowering therapy alone.
 In a subset of patients in the top TG tertile (≥ 198 mg/dl) and the
bottom HDL-C tertile (< 33 mg/dl), ER niacin showed a trend
toward benefit (hazard ratio: 0.74, p = 0.073).
 On-trial LDL-C levels, non-HDL-C levels, and the total
cholesterol/HDL-C ratio were positively associated with CV events
in the control group, but these relationships were absent in the
ER niacin
 These data suggest that the high TG/low HDL group are highest
risk, and may get benefit from niacin on top of statin therapy.
Guyton J et al J Am Col2013; 62:1580-4.
Fibrates: Subgroup Analysis
Fibrates
• In ACCORD Lipid – overall event rate was
11.3% in the simvastatin monotherapy
group and 10.5% in the simvastatin/
fenofibrate group (p=0.32).
• In the subgroup with TG > 200 mg/dL and
HDL-C < 35 mg/dL event rate was 17.3%
(+53%) in the simvastatin monotherapy
group and 12.4% (-28%) in the simvastatin/
fenofibrate group (p=0.03).
• Similar observations in BIP and FIELD
Ginsberg HN et al New Engl J Med 2010;362:1563-9
Secondary Causes of Dyslipidemia
•
Secondary Causes of Elevated LDL-C: obesity,
increased intake saturated fat & trans fats,
hypothyroidism, diuretics, cyclosporin,
glucocorticoids, amiodorone, biliary obstruction,
nephrotic syndrome, pregnancy, & anorexia
• Secondary Causes of Elevated Triglycerides: obesity,
diabetes, high sugar intake, excessive alcohol intake,
hypothyroidism, oral estrogens, glucocorticoids, bile
acid sequestrants, protease inhibitors, retinoic acid,
anabolic steroids, sirolimus, raloxifene, tamoxifen,
beta blockers (except carvedilol), thiazides, and
pregnancy.
Cholesterol-Carrying Lipoproteins
VLDL
0.95
VLDL
Remnants
Particle Density, g/mL
1.006
Chylomicron
Chylomicron
VLDL
VLDL
IDL
Chylomicron
Remnants
1.02
LDL
1.06
1.10
HDL2
Lp(a)
HDL3
Heart disease patients often have
increased remnants lipoproteins,
small dense LDL), and Lp(a), and
decreased large HDL)
1.20
5
10
20
40
60
Particle Size - Diameter, nm
80
1000
Genest et al Circulation 1992;85:2025, Campos et al, ATVB 1992; 12:187, Schaefer et al JAMA 1994;59:32, McNamara
et al Atherosclerosis 2001;154:229, Asztalos et al ATVB 2004;24:2181, & Ai et al Clin Chem 2010; 56:967-76.
IVUS detects angiographically “silent” atheroma – to get
regression LDL-C needs to be < 70 mg/dL and HDL-C
needs to be raised by > 8% - only 2/3 get regression with
aggressive statin treatment
IVUS
Angiogram
No
evidence
of disease
Little
evidence
of disease
IVUS
Atheroma
IVUS = intravascular ultrasound, Nissen S, Yock P. Circulation 2001; 103:
604–616, Nicholls S et al ASTEROID and SATURN Studies 2007, 2011.
Statin Meta Analyses – Oxford
“For every 40 mg/dL
reduction in LDL-C, there
is a 20% reduction in
cardiovascular endpoints.”
Everyday in the U.S.1
>55
5200
People are diagnosed
with type 2 diabetes
Every 17 seconds,
someone in the U.S. is
diagnosed with diabetes2
1. http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf (Accessed March 2011)
2. http://www.cdc.gov/media/pressrel/2010/r101022.html (Accessed September 2011)
People go blind
>120 People begin dialysis
>230 People undergo amputations
Diabetes now kills more
people each year than breast
cancer and AIDS combined.2
Positive Effects of Lifestyle Changes
Diabetes Prevention Project
• 3234 prediabetic subjects with  fasting glucose (100 –
125 mg/dL) and body mass index of 34.0 kg/m2
• Lifestyle modification over 3 years: (goal of 7% weight-loss
and > 150 min. physical activity /week, fat < 25% of
calories, 500 calorie deficit/day vs. metformin vs. placebo
• New Development of Diabetes Mellitus
• 33% over 3 years in usual care group
• 23% over 3 years in metformin group (-31%)
• 14% over 3 years in lifestyle group (-58%)
• Boston Heart Diagnostics - similar lifestyle program
Diabetes Prevention Program Research Group. New Eng J Med 2002; 346:393-9.
Clinical Studies Demonstrate
Prevention is Possible
*Currently, no medications are FDA-approved for the prevention of diabetes
1.Diabetes Prevention Program Research Group. NEJM . 2002; 346:393-403. 2. Tuomilehto J, et al. NEJM. 2001;
344:1343-1350. 3. DREAM Trial Investigators. Lancet. 2006; 368:1096-1105. 4. Zinman B, et al. Lancet. 2010; 376:
103-111. 5. DeFronzo R, et al. N Engl J Med. 2011; 365:182-184
9
CARDIOMETABOLIC IMPACT
• Lancet 1999; 354:617-621
– DECODE Study Group
– 10-year follow-up of Normal Glucose Tolerance, Impaired
Glucose Tolerance and Diabetes Mellitus
– Two-fold increase risk of CVD for IGT vs. NGT
– Four-fold increase risk of CVD for DM vs. NGT
• 80% of diabetics die of CVD
MI (60%) / CVA (20%)
CARDIOMETABOLIC IMPACT
• More than 70% of Coronary Artery Disease/Acute
Coronary Syndrome sufferers are insulin
resistant!
– Diabetes Care 2008; 31:1955-1959
– Lancet 2007; 370:667-675
• Every 18mg/dl above 140mg/dl at 2-hour plasma
glucose increases cardiovascular and all-cause
death rates by 26% over 6-7 years
– Diabetes Care 2009; 32:1721-1726
LAB CLUES
• Triglycerides >130 mg/dl
• Low HDL/LOW HDL2b
• High sdLDL
• FPG>88mg/dl
• Fasting Insulin
– >16microU/ml
•
Triglyceride/HDL Ratio
(Ethnic variation)
•
•
GGTP >21mg/dl women;
ALT
• HgB A1C > 5.6%
• ^ MACR
>47mg/dl men
• ^ hsCRP
> 20mg/dl women
• ^ Fibrinogen
> 34mg/dl men
• ^ Lp-PLA2
• Decreased Vitamin D
Examples of
Coronary Artery Scans
NO
CALCIFICATION
“zero score”
MODERATE
SIGNIFICANT
CALCIFICATION
CALCIFICATION
“high score”
Primary Prevention of Cardiovascular Disease
For persons aged 50 years or older without symptomatic
cardiovascular disease, we suggest low-dose aspirin 75
to 100 mg daily over no aspirin therapy (Grade 2B).
Remarks: Aspirin slightly reduces total mortality regardless of
cardiovascular risk profile if taken over 10 years. In people at moderate to
high risk of cardiovascular events, the reduction in myocardial infarction
(MI) is closely balanced with an increase in major bleeds. Whatever their
risk status, people who are averse to taking medication over a prolonged
time period for very small benefits will be disinclined to use aspirin for
primary prophylaxis. Individuals who value preventing an MI substantially
higher than avoiding a GI bleed will be, if they are in the moderate or high
cardiovascular risk group, more likely to choose aspirin.
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<.000
1
1.5
2.0
0.5
1.0
Antiplatelet Better Antiplatelet Worse
Antithrombotic Trialist Collaboration. BMJ 2002;324:71-86
Aspirin Primary
Recommendations
Prevention (Women)
I IIa IIb III
Aspirin (81 mg daily or 100 mg every
other day) in at risk women >65 years of
age
I IIa IIb III
Aspirin in at risk women <65 years of age
for ischemic stroke prevention
I IIa IIb III
Aspirin in optimal risk women <65 years of
age
CHD=Coronary heart disease
Aspirin Recommendations
Primary Prevention (Men*)
I IIa IIb III
Aspirin (75-162 mg daily) in those at
intermediate risk (10 year risk of CHD >10%)
*Specific guideline recommendations for men do not exist, but these guidelines are based on previous
general (not gender specific) primary prevention guidelines
CHD=Coronary heart disease
Secondary Prevention
CVD Risk Prediction
The best predictor of future CHD is the
presence of pre-existing disease. There is a
high correlation between carotid and coronary
artery atherosclerosis. Carotid ultrasound
remains the most cost-effective strategy to
detect the presence of early atherosclerosis.
Another option is cardiac calcium scoring.
Effect of Smoking Cessation on Mortality After Myocardial Infarction: Meta-analysis of
Cohort Studies
Arch Intern Med. 2000;160(7):939-944. doi:10.1001/archinte.160.7.939
Table Title:
Benefit of Smoking Cessation on Mortality After Myocardial Infarction: Results of the Primary Studies*
Date of download: 11/2/2014
Copyright © 2014 American Medical
Association. All rights reserved.
Aspirin Recommendations (Cont’d)
Secondary Prevention
I IIa IIb III
Aspirin (75-162 mg daily) if known CHD/ASVD
I IIa IIb III
Aspirin (162-325 mg daily) for at least 3
months after sirolimus-eluting stent
implantation and at least 6 months after
paclitaxel-eluting stent implantation after
which aspirin (75-162 mg daily) should be
continued indefinitely
ASVD=Atherosclerotic vascular disease, CABG=Coronary artery bypass graft,
CHD=Coronary heart disease
Aspirin Recommendations (Cont’d)
Secondary Prevention
I IIa IIb III
Aspirin (75-162 mg daily) as the initial dose
after stent implantation in those at higher
bleeding risk
I IIa IIb III
Aspirin (100-325 mg daily) following CABG
surgery*
*To be administered within the first 48 hours after surgery in
order to reduce the risk of saphenous vein graft failure.
Doses >162 mg/day may be continued for up to one year
P2Y12 Receptor Antagonist
Recommendations
I IIa IIb III
I IIa IIb III
I IIa IIb III
Secondary Prevention
Clopidogrel (75 mg daily; Class I, Level B), prasugrel* (10
mg daily; Class I, Level C), or ticagrelor (90 mg twice daily;
Class I, Level C) if aspirin intolerance or a true aspirin
allergy following a NSTE-ACS
Clopidogrel (75 mg daily) or ticagrelor (90 mg twice daily)
in addition to aspirin for up to 1 year following a NSTE-ACS
managed conservatively
*In PCI treated patients
NSTE-ACS=Non ST-segment elevation acute coronary
syndrome; PCI=Percutaneous coronary intervention,
STEMI=ST-segment elevation myocardial infarction
Source: Jneid H et al. JACC 2012;60:645-681
P2Y12 Receptor Antagonist
Recommendations
Secondary Prevention
I IIa IIb III
Clopidogrel (75 mg daily), prasugrel (10 mg daily), or
ticagrelor (90 mg twice daily) in addition to aspirin for 1
year following PCI for a NSTE-ACS† or a STEMI‡
I IIa IIb III
I IIa IIb III
Clopidogrel (75 mg daily) in addition to aspirin for a
minimum of 14 days (Class I, Level A) and up to 1 year
(Class I, Level C) following fibrinolytic therapy for a
STEMI‡
NSTE-ACS=Non ST-segment elevation acute coronary
syndrome; PCI=Percutaneous coronary intervention,
STEMI=ST-segment elevation myocardial infarction
Sources:
H et al. JACC 2012;60:645-681
‡O’Gara PT et al. JACC 2013;61:e78-e140
†Jneid
P2Y12 Receptor Antagonist
Recommendations (Cont’d)
Secondary Prevention
I IIa IIb III
If the risk of morbidity because of bleeding outweighs the
anticipated benefit afforded by a P2Y12 receptor antagonist,
earlier discontinuation should be considered
I IIa IIb III
Continuation of a P2Y12 receptor antagonist beyond 1 year
may be considered in patients undergoing drug eluting stent
placement
Sources:
Kushner F et al. JACC 2009;54:2205-2241
Jneid H et al. JACC 2012;60:645-681
O’Gara PT et al. JACC 2013;61:e78-e140
ACE Inhibitor Recommendations
Secondary Prevention
I IIa IIb III
An ACE inhibitor should be started and continued indefinitely
in all patients with left ventricular ejection fraction <40% and
in those with hypertension, DM, or CKD, unless
contraindicated
I IIa IIb III
An ACE inhibitor in all other patients
ACE=Angiotensin converting enzyme, CKD=Chronic kidney disease,
DM=Diabetes mellitus, LVSD=Left ventricular systolic dysfunction
Source: Smith SC Jr. et al. JACC 2011;58:2432-2446
Angiotensin Receptor Blocker
Recommendations
Secondary Prevention
I IIa IIb III
An ARB in patients who have HF or who have had a MI
with left ventricular ejection fraction <40% and who are
ACE-inhibitor intolerant
I IIa IIb III
An ARB in other patients who are intolerant of an ACE
inhibitor
I IIa IIb III
Use of an ARB in combination with an ACE inhibitor is not
well established in those with systolic heart failure
ACE=Angiotensin converting enzyme, ARB=Angiotensin
receptor blocker, HF=Heart failure, MI=Myocardial infarction
Source: Smith SC Jr. et al. JACC 2011;58:2432-2446
Beta-Blocker Recommendations
Secondary Prevention
I IIa IIb III
Beta-blocker should be used in all patients with LVSD
(ejection fraction <40%) with HF or prior MI, 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 for 3 years in all patients with normal left
ventricular function who have had a MI or ACS
I IIa IIb III
Beta-blocker beyond 3 years as chronic therapy in all
patients with normal left ventricular function who have had a
MI or ACS
*Relative contraindications include asthma, chronic obstructive
pulmonary disease, insulin dependent diabetes mellitus, severe
peripheral arterial disease, and a PR interval >0.24 seconds
ACS=Acute coronary syndrome, HF=Heart failure, LVSD=Left
ventricular systolic dysfunction, MI=Myocardial infarction
Source: Smith SC Jr. et al. JACC 2011;58:2432-2446
Cardiac Rehabilitation:
Greater Benefit with Greater Attendance
Death (%)
Myocardial infarction (%)
Observational study of 30,161 Medicare patients attending at least 1
phase II cardiac rehabilitation session
Years after Index Date
Years after Index Date
There is a strong dose-response relationship between the number of
cardiac rehabilitation sessions attended and long-term CV outcomes
CV=Cardiovascular
Source: Hammill BG et al. Circulation 2010;121:63-70
What Diagnoses are Covered?
• Medicare Guidelines: 36 sessions per year after cardiac event
− Angina
− Myocardial Infarction
− Coronary Artery Bypass Graft
− Heart Transplant
− Valve Surgery
− Stent
− Coronary Artery Disease (CAD)
•
Private insurance coverage may vary and may cover
- PAD
- CHF
- Cardiomyopathy
- Valvular disease
Utilization Benefits:
• Reduced risk of fatal MI (<25%)
• Decreased severity of angina & need for antiangina meds
• Decreased hospitalizations
• Decreased cost of physician office visits &
hospitalizations (<35%)
• Fewer ER visits
Patient Benefits:
• Improved functional capacity
• Increased knowledge of heart disease
• Improved adherence to positive lifestyle
changes
• Better compliance with medical regime
• Increased self-esteem and confidence
• Reduced subsequent morbidity & mortality r/t
CAD
Lifestyle Benefits:
Risk Factor and Lifestyle Modification
• Smoking cessation
• Lipid improvement
• Blood pressure control
• Exercise guidance
• Weight management
• Diabetes control
• Stress management
Antioxidant Vitamin Guidelines
Secondary Prevention
I IIa IIb III
Antioxidant vitamin supplements (e.g., vitamins E, C, or
beta carotene) should not be used for secondary prevention
in NSTE-ACS.
NSTE-ACS=Non-ST-segment elevation acute coronary syndrome
Anderson JL et al. JACC 2007;50:652-726
B Vitamins and Folic Acid Guidelines
I IIa IIb III
Secondary Prevention
Folic acid, with or without B6 and B12, should not be used for
secondary prevention in NSTE-ACS
NSTE-ACS=Non-ST-segment elevation acute coronary syndrome
Anderson JL et al. JACC 2007;50:652-726
Hormone Replacement Therapy
Guidelines
Secondary Prevention
I IIa IIb III
I IIa IIb III
HRT with estrogen plus progestin, or estrogen alone, should
not be given de novo to postmenopausal women after
NSTE-ACS for secondary prevention of coronary events.
Postmenopausal women who are already taking estrogen
plus progestin, or estrogen alone, at the time of NSTE-ACS
in general should not continue HRT. Women who are more
than 1-2 years past the initiation of HRT who wish to
continue therapy for another compelling indication should
weigh the risks and benefits, recognizing the greater risk of
CV events and breast cancer (combination therapy) or
stroke (estrogen).
CV=Cardiovascular, HRT=Hormone replacement therapy, NSTEACS=Non-ST-segment elevation acute coronary syndrome
Anderson JL et al. JACC 2007;50:652-726
Nonsteroidal Anti-inflammatory
Drug Guidelines
Secondary Prevention
I IIa IIb III
I IIa IIb III
At hospital discharge, the patient’s need for treatment of
chronic musculoskeletal discomfort should be assessed,
and a stepped-care approach to treatment should be used,
starting with acetaminophen, small doses of narcotics, or
nonacetylated salicylates.
It is reasonable to use nonselective NSAIDs, such as
naproxen, if initial therapy with acetaminophen, small doses
of narcotics, or nonacetylated salicylates is insufficient.
NSAIDs=Nonsteroidal anti-inflammatory drugs
Anderson JL et al. JACC 2007;50:652-726
Nonsteroidal Anti-inflammatory
Drug Guidelines (Cont’d)
Secondary Prevention
I IIa IIb III
It is reasonable to use nonselective NSAIDs, NSAIDs with
increasing degrees of relative COX-2 selectivity may be
considered for pain relief only for situations in which
intolerable discomfort persists despite attempts at steppedcare therapy with acetaminophen, small doses of narcotics,
nonacetylated salicylates, or nonselective NSAIDs. In all
cases, the lowest effective doses should be used for the
shortest possible time
COX-2-Cyclooxygenase 2, NSAIDs=Nonsteroidal anti-inflammatory drugs
Anderson JL et al. JACC 2007;50:652-726
Aldosterone Antagonist Guidelines
Secondary Prevention
I IIa IIb III
Use of aldosterone blockade in post-MI patients without
significant renal dysfunction* or hyperkalemia** is
recommended in patients who are already receiving
therapeutic doses of an ACE inhibitor and beta-blocker,
who have a LV EF <40%, and who have either DM or HF
*Estimated creatinine clearance should be >30 ml/min
**Potassium should be <5.0 mEq/L
ACE=Angiotensin converting enzyme, DM=Diabetes
mellitus, EF=Ejection fraction, HF=Heart failure,
LV=Left ventricular, MI=Myocardial infarction
Source: Smith SC Jr. et al. JACC 2011;58:2432-2446
Digoxin Guidelines
I IIa IIb III
Secondary Prevention
Digoxin in those with symptomatic HF and LVSD (EF
<45%) to reduce hospitalizations for HF*
I IIa IIb III
Digoxin in those with asymptomatic LVSD and normal
sinus rhythm
*Contraindications include significant sinus or atrioventricular
block unless a permanent pacemaker is present
EF=Ejection fraction, HF=Heart failure, LVSD=Left ventricular systolic function
Source: Hunt SA et al. Circulation 2005;112:e154-235
Implantable Cardioverter Defibrillator
Guidelines
Secondary Prevention
I IIa IIb III
Patients with an ejection fraction of <35% who are at
least 40 days post-MI and are in NYHA functional
Class II or III
Patients with an ejection fraction of <30% who are at
least 40 days post-MI and are in NYHA functional
Class I
I IIa IIb III
Patients with nonsustained VT due to prior MI, an
ejection fraction of <40%, and inducible sustained VT
or VF at EP study
EP=Electrophysiology, MI=Myocardial infarction, NYHA=New York Heart
Association, VF=Ventricular fibrillation, VT=Ventricular tachycardia
Epstein AE et al. Circulation 2008;117:e350-408
Influenza Vaccination Guidelines
I IIa IIb III
Secondary Prevention
Patients with cardiovascular disease should have an
annual influenza vaccination
Source: Smith Jr SC et al. JACC 2011;58:2432-2446
Evidence for Current Cardiovascular
Disease Prevention Guidelines
Room for Improvement
Utilization of Risk Reducing Medications
at Discharge in Acute Coronary Syndromes
ACTION Registry/Get With The Guidelines (GWTG) Data
86%
NSTEMI
STEMI
NSTEMI=Non-ST-segment elevation myocardial infarction,
STEMI=ST-segment elevation myocardial infarction
Source: ACTION Registry-GWTG DATA: January 1, 2010 –
December 31, 2010. Courtesy of NCDR 10/21/2011
Strategies for Initiating and Optimizing
Cardiovascular Therapies
 Hospital based performance improvement systems
 In-hospital initiation of CV protective therapies
 Pay for performance/financial incentives
 Nurse or pharmacist managed outpatient CV prevention programs
 Preventive cardiology and cardiac rehabilitation centers
 Virtual prevention clinics using electronic medical record systems
 Combination of CV protective medications
CV=Cardiovascular
Thank You