Management of Coronary

Artery Disease:

Saravanan Kuppuswamy MD
Division of Cardiology
Department of Internal Medicine
University of Missouri Hospital
Coronary blood supply
Micro circulation
 Temporal Trends in CAD
• CHD is the leading cause of death in adults in
US (1/3 of all deaths in subjects over age 35)

• Mortality rates for cardiovascular death has

fallen in most developed countries 24-28% since
1975

• Estimated that 45 percent of mortality reduction

in CHD is due to improvement of medical
therapy and 55% is due to risk factor
modification
 Etiology
• Congenital

• Acquired
– Infection
– Inflammation
– Neoplastic
 Management of CAD
• Acute

• Chronic
 ACS: The Tip of the
Atherothrombotic “Iceberg”
Acute Plaque Rupture
(UA/NSTEMI/STEMI)

Clinical

Subclinical

Presence of Multiple Persistent Hyperreactive Vascular

Coronary Plaques Platelets Inflammation
ACS=acute coronary syndrome.
UA=unstable angina.
Bhatt DL. J Invasive Cardiol. 2003;15:3B-9B. NSTEMI=non-ST-segment elevation myocardial infarction.
STEMI=ST-segment elevation myocardial infarction.
 Chronic stable angina
• Levine’s sign
• Exercise capacity may vary
• Relieved by nitrates
CCS classification
Applying Classification of Recommendations
and Level of Evidence
Class I Class IIa Class IIb Class III

Benefit >>> Risk Benefit >> Risk Benefit ≥ Risk Risk ≥ Benefit
Additional studies Additional studies No additional studies
with focused with broad needed
objectives needed objectives needed;
Additional registry
data would be
helpful

Procedure or IT IS REASONABLE Procedure or

treatment SHOULD to perform Procedure or treatment should
be performed or procedure or treatment NOT be performed or
administered administer treatment MAY BE administered SINCE
CONSIDERED IT IS NOT HELPFUL
AND MAY BE
HARMFUL
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
ABCDE Of Management
A
Antiplatelet Agents / Anticoagulation
Recommendations
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

Post-PCI-stented patients should receive 325 mg

I IIa IIb III 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

*Aspirin was the predominant antiplatelet agent studied 0.0 0.5 1.0 1.5 2.0
**Vascular events include MI, stroke, or death
Antiplatelet better Control better
Antithrombotic Trialist Collaboration. BMJ 2002;324:71–86.
 Aspirin Evidence: Dose and Efficacy
Indirect Comparisons of Aspirin Doses on Vascular Events
in High-Risk Patients
Odds Ratio for
Aspirin Dose No. of Trials (%) Vascular Events
500-1500 mg 34 19

160-325 mg 19 26

75-150 mg 12 32

<75 mg 3 13

Any aspirin 65 23
P<.0001
0 0.5 1.0 1.5 2.0
Antiplatelet Better Antiplatelet Worse
Antithrombotic Trialists Collaboration. BMJ. 2002;324:71-86
Mechanism of action of nitrates
B
-blocker Recommendations
-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

 -blocker Evidence
Summary of Secondary Prevention Trials of -blocker Therapy
Phase of Total #
Treatment Patients RR (95% CI)

Acute 28,970 0.87 (0.77-0.98)

treatment

Secondary 24,298 0.77 (0.70-0.84)

prevention

Overall 53,268 0.81 (0.75-0.87)

0.5 1.0 2.0

RR of death
-blocker Placebo
CI=Confidence interval, RR=Relative risk better better
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.
 -blocker Evidence: Post MI with
Left Ventricular Dysfunction
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
Proportion Event-free

0.95
n=975
0.9 Carvedilol
0.85 n=984

0.8
0.75 Placebo
RR 0.77 P=.03
0.7
0 0.5 1 1.5 2 2.5
Years
The CAPRICORN Investigators. Lancet. 2001;357:1385–1390.
-blocker Evidence: Benefit in HF and LVSD
HF Patients Follow-up Mean Effects on Outcomes
Study Drug Severity (n) (years) Dosage

CIBIS Bisoprolol* Moderate- 641 1.9 3.8 All cause mortality

Severe mg/day 22% (p=NS)

CIBIS-II Bisoprolol* Moderate- 2,647 1.3 7.5 All cause mortality

Severe mg/day 34% (P<0.0001)
BEST Bucindolol* Moderate- 2,708 2.0 152 All cause mortality
Severe mg/day 10% (p=NS)

MERIT-HF Metoprolol Mild- 3,991 1.0 159 All cause mortality

succinate# Moderate mg/day 34% (P=0.0062)
MDC Metprolol Mild- 383 1.0 108 Death or Need for Tx
tartrate* Moderate mg/day 30% (P=NS)

CAPRICORN Carvedilol Mild 1,989 1.3 40 All cause mortality

mg/day 23% (P =0.03)

US Carvedilol Carvedilol Mild- 1,094 0.5 45 All-cause mortality†

Moderate mg/day 65% (P=.0001)
COPERNICUS Carvedilol Severe 2,289 0.9 37 All-cause mortality
*Not an approved indication
mg/day 35% (P =0.0014)
†
Not a planned end point.
#
Not approved for severe HF or mortality reduction alone
 Blood Pressure Control Recommendations
Goal: <140/90 mm Hg or <130/80 if
diabetes or chronic kidney disease
Blood pressure 120/80 mm Hg or greater:
I IIa IIb III
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

I IIa IIb III 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
 Blood Pressure: Lower is Better
Ischemic Heart Disease Mortality
Ischemic Heart Disease Mortality

Ischemic Heart Disease Mortality

Age at Risk (Y) Age at Risk (Y)
80-89 80-89
256 256
128 70-79 128 70-79

64 60-69 64 60-69

32 50-59 32 50-59
16 40-49 16 40-49
8 8
4 4
2 2
1 1
0 0
120 140 160 180 70 80 90 100 110
Usual Systolic BP (mm Hg) Usual Diastolic BP (mm Hg)
BP=Blood pressure
Prospective Studies Collaboration. Lancet. 2002;360:1903-1913
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 0.5 1.0 1.5 2.0

CHD=Coronary heart disease Better than placebo Worse than placebo
He J et al. Am Heart J 1999; 138:211-219
 JNC VII Guidelines for Management and Treatment
Initial drug therapy
SBP* DBP* Lifestyle
BP classification With compelling
mmHg mmHg modification
indications
Normal <120 <80 Encourage
Pre- 120–139 80–89 Yes Drug(s) for compelling
hypertension indications. ‡

Stage 1 140–159 90–99 Yes Drug(s) for the

Hypertension
compelling indications.‡

Stage 2 >160 >100 Yes Other antihypertensive

Hypertension drugs (diuretics, ACEI,
ARB, BB, CCB) as
needed.

ACEI=Angiotensin converting enzyme inhibitor, ARB=Angiotensin receptor blocker, BB=-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
 JNC VII Lifestyle Modifications for BP Control
Modification Recommendation Approximate SBP
Reduction Range
Weight reduction Maintain normal body weight (BMI=18.5- 5-20 mmHg/10 kg weight
24.9) lost
Adopt DASH Diet rich in fruits, vegetables, low fat 8-14 mmHg
eating plan dairy and reduced in fat
Restrict sodium <2.4 grams of sodium per day 2-8 mmHg
intake
Physical activity Regular aerobic exercise for at least 30 4-9 mmHg
minutes on most days of the week
Moderate alcohol <2 drinks/day for men and <1 drink/day 2-4 mmHg
consumption for women

BMI=Body mass index, SBP=Systolic blood pressure

Chobanian AV et al. JAMA. 2003;289:2560-2572
 JNC VII Compelling Indications for Drug Classes
Compelling Indication Initial Therapy Options Clinical-Trial Basis
Heart Failure Diuretic, BB, ACEI, MERIT-HF, COPERNICUS, CIBIS,
ARB, Aldo Ant 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, NKF-ADA Guideline,

ARB, CCB UKPDS, ALLHAT

NKF Guideline, Captopril Trial,

Chronic Kidney Disease ACEI, ARB RENAAL, IDNT, REIN, AASK

Recurrent Stroke Prevention 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
C
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.
 Cigarette Smoking Cessation: Risk of Non-fatal MI*
Study RR (95% Cl)
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 (0.46-1.37)
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 1.0 10
Ceased smoking Continued smoking
*Includes those with known coronary heart disease
Critchley JA et al. JAMA. 2003;290:86-97. CI=Confidence interval, RR=Relative risk
 Lipid Management Goals: NCEP

Consider
Risk Category LDL-C and non-HDL- Initiate TLC Drug Therapy
C Goal

High risk: <100 mg/dL 100 mg/dL >100 mg/dL

CHD or CHD risk equivalents if TG > 200 mg/dL, (<100 mg/dL: consider drug
(10-year risk >20%) non-HDL-C should options)
and be < 130 mg/dL
Very high risk: <70 mg/dL, All patients >100 mg/dL
ACS or established CHD non-HDL-C < 100 (<100 mg/dL: consider drug
plus: multiple major risk mg/dL options)
factors (especially diabetes) or
severe and poorly controlled
risk factors
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.

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.
 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

I IIa IIb III drug therapy

If on-treatment LDL-C > 100 mg/dL, intensify LDL-

lowering drug therapy (may require LDL lowering drug
combination)
I IIa IIb III
If baseline is LDL-C 70 to 100 mg/dL, it is reasonable to
treat to LDL < 70 mg/dL
When LDL lowering medications are used, obtain at least a 30-40% reduction in LDL-C
levels.
Lipid Management Recommendations
I IIa IIb III

If TG are 200-499 mg/dL, non-HDL-C should be < 130 mg/dL

I IIa IIb III

Further reduction of non-HDL to < 100 mg/dL is reasonable

Therapeutic options to reduce non-HDL-C:

More intense LDL-C lowering therapy I (B) or
Niacin (after LDL-C lowering therapy) IIa (B) or
Fibrate (after LDL-C lowering therapy) IIa (B)
I IIa IIb III If TG are > 500 mg/dL, therapeutic options to prevent
pancreatitis are fibrate or niacin before LDL lowering therapy;
and treat LDL-C to goal after TG-lowering therapy. Achieve non-
HDL-C < 130 mg/dL, if possible
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 Statin Placebo Statin Better Statin Worse
LDL-C (mg/dL) (n = 10,269) (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%) 0.76 (0.72–0.81)

P<0.0001
All patients 2033 (19.8%) 2585 (25.2%)

0.4 0.6 0.8 1.0 1.2 1.4

CAD=Coronary artery disease, CI=Confidence interval, DM=Diabetes mellitus,
HPS Collaborative Group. Lancet 2002;360:7-22
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
30
Atorvastatin
16% RRR
25 Pravastatin
Recurrent MI or
Cardiac Death

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
 HMG-CoA Reductase Inhibitor: Secondary
Prevention
Relationship between LDL Levels and Event Rates in Secondary Prevention Trials
of Patients with Stable CHD
30 Statin 4S
Placebo
25
4S
Event (%)

20
LIPID
15 LIPID
CARE CARE
10 HPS HPS
TNT (atorvastatin 10 mg/d)
5 TNT (atorvastatin 80 mg/d)

0
0 70 90 110 130 150 170 190 210
LDL-C (mg/dL)
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

 Lipid Management Pharmacotherapy
Patient
Therapy TC LDL HDL TG
tolerability

Statins*  19-37%  25-50%  4-12%  14-29% Good

Ezetimibe  13% 18% 1%  9% Good

Bile acid Neutral or

7-10% 10-18% 3% Poor
sequestrants 
Reasonable to
Nicotinic acid  10-20%  10-20%  14-35%  30-70%
Poor

Fibrates 19% 4-21% 11-13% 30% Good

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.

 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

D
ATP III Dietary Recommendations
Nutrient Recommended Intake
Saturated fat* <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 20–30 g/d
Protein ~15% of total calories
Cholesterol <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-
 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 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.
I IIa IIb III 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 meters 2.
Overweight state is defined by BMI=25-30 kg/m2. Obesity is defined by a BMI >30 kg/m2.
 CV Risk Increases with Body Mass Index
Hemorrhagic Ischemic Ischemic Heart
Stroke Stroke Disease
4.0 4.0 4.0
Hazard Ratio

2.0 2.0 2.0

1.0 1.0 1.0

0.5 0.5 0.5

16 20 24 28 32 36 16 20 24 28 32 36 16 20 24 28 32 36

CV=Cardiovascular
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
 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.
Metabolic Syndrome: Risk of Developing DM
Diabetes Prevention Program (DPP)
3,234 patients with elevated fasting and post-load glucose levels randomized to placebo,
metformin (850 mg twice daily), or lifestyle modification* for 2.8 years

Placebo
40
Metformin
Incidence of DM (%)

Lifestyle modification

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
 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
E
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
I IIa IIb III activities

Advise medically supervised programs for high-risk patients

 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

 QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Renin-Angiotensin-Aldosterone System
Blockers Recommendations
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
 QuickTime™ and a
decompressor
are needed to see this picture.
STRIVE TM
 The Spectrum of ACS
Non-cardiac Stable UA NSTEMI STEMI
chest pain angina

Clinical finding Atypical Exertional Rest pain, Post-MI, Ongoing

pain pain DM, Prior Aspirin pain
Negative ST-T wave ST
EKG changes elevation

Serum markers Negative Positive

Risk assessment Low Low Medium-high STEMI

probability risk risk

Diagnostic Aspirin, heparin/low-molecular-

rule out MI/ACS Thrombolysis
weight heparin (LMWH) +
pathway Primary PCI
clopidogrel
Anti-ischemic Rx
Early conservative therapy
Negative
Aspirin + GP IIb/IIIa inhibitor
clopidogrel + heparin/
Discharge LMWH + anti-ischemic Rx
DM=diabetes mellitus. Early invasive Rx
Cannon, Braunwald. Heart Disease. 2001.
Acute Coronary Syndromes:

Management of STEMI
Balloon angioplasty
Stents
Acute Coronary Syndromes:

Management of UA/NSTEMI
 Acute Management of UA/NSTEMI

Anti-Ischemic Therapy
• Oxygen, bed rest, ECG monitoring
• Nitroglycerin
 -Blockers
• ACE inhibitors

Antithrombotic Therapy
• Antiplatelet therapy
• Anticoagulant therapy
UA, unstable angina; NSTEMI, non-ST-segment elevation myocardial infarction; ECG, electrocardiogram;
ACE, angiotensin-converting enzyme.
Braunwald E, et al. J Am Coll Cardiol. 2000;36:970-1062.
 Rationale for Use: Pharmacologic
Intervention in Thrombosis
Coagulation Platelets
cascade Collagen Leukocytes

LMWH
Platelets

Tissue factor
LMWH TFPI
Thromboxane A vWF ADP
UFH 2

Aspirin Thienopyridines
Factor Xa
Activated platelets
in
ro mb GP IIb/IIIa
t i-th
A n
Prothrombin
inhibitors
LMWH
UFH Fibrinogen cross-linking
Ant
i-th Thrombin
ro m
bin
Platelet aggregation
Direct
thrombin
inhibitors Fibrinogen Fibrin Thrombus Fibrin
Plasmin degradation
UFH=unfractionated heparin.
LMWH=low-molecular-weight heparin
ADP=adenosine diphosphate.
TFPI=tissue factor pathway inhibitor
Thrombolytics
Selwyn A. Am J Cardiol. 2003;91:3H-11H.
 Efficacy of Aspirin Doses on Vascular
Events in High Risk Patients
Aspirin Dose # Trials OR* (%) Odds Ratio

500–1500 mg 34 19
160–325 mg 19 26
75–150 mg 12 32
<75 mg 3 13
Any aspirin 65 23
0 0.5 1.0 1.5 2.0
Anti - platelet Better Anti - platelet
Worse

*Odds reduction. Treatment effect P < 0.0001.

Adapted with permission from the BMJ Publishing Group. Anti-thrombotic Trialists’ Collaboration. BMJ.
2002;324:71-86.
 Comparison of Heparin + ASA vs ASA Alone
B Theroux

B RISC

B Cohen 1990

B ATACS
B Holdright
B Gurfinkel
Summary Relative Risk
0.67 (0.44-0.1.02) B

0.1 1 10
Heparin + ASA RR: ASA Alone
55/698=7.9% Death/MI 68/655=10.4%
ASA, acetylsalicylic acid; RISC, Research on InStability in Coronary artery disease; ATACS, Antithrombotic
Therapy in Acute Company Syndromes; RR, relative risk; MI, myocardial infarction.
Oler A, et al. JAMA. 1996;276:811-815. (with permission)
 TIMI IIB/ESSENCE Metanalysis:
Enoxaparin vs Unfractionated Heparin

Day UFH ENOX Death or MI OR % P

(%) (%) (95 CI)
2 1.8 1.4 0.80 (0.55-1.16) 20 .24

8 5.3 4.1 0.77(0.62-0.95) 23 .02

14 6.5 5.2 0.79 (0.65-0.96) 21 .02

43 8.6 7.1 0.82 (0.69-0.97) 18 .02

0.5 1 2
Favors Favors
OR
ENOX UFH
TIMI, Thrombosis in Myocardial Infarction; ESSENCE, Efficacy and Safety of Subcutaneous Enozapam in
Non–Q-Wave Coronary Events; UHF, unfractionated heparin; ENOX, enoxaparin; MI, myocardial infarction;
OR, odds ratio.
Antman EM, et al. Circulation. 1999;100:1602-1608. (with permission)
 LMWH Limitations
• Indirect inhibition: dependent on antithrombin
• Inability to inhibit clot-bound thrombin
• Catheterization lab: slower onset, longer half-life,
and with enoxaparin, no standard test to
measure levels/effect
• CABG: concerns regarding the long half-life
• Monitoring for Factor Xa: possible, but what is
the therapeutic target, increased time, expense?
• Not all LMWHs are the same
CABG=coronary artery bypass graft.
 CURE: Primary Endpoint:
MI/Stroke/CV Death
0.14
Placebo 20%
0.12 + Aspirin* Relative-risk
Cumulative Hazard Rate

Reduction
0.10
P<0.001
0.08 N=12,562
Clopidogrel
+ Aspirin*
0.06

0.04

0.02

0.00
0 3 6 9 12
Months of Follow-Up
*Other standard therapies were used as appropriate.
CV=cardiovascular.
CURE Trial Investigators. N Engl J Med. 2001;345:494-502.
Early Use of GP IIb/IIIa Inhibition Improves
PCI: CAPTURE, PURSUIT, PRISM-PLUS

Before PCI Post-PCI

10% 10%
Placebo
8% GP IIb/IIIa Inhibitor 8% 8.0%

Death/MI
Death/MI

6% 6%
n=12,296 4.9%
p=0.001 4.3%
4% 4%
2.9% n=2754
2% 2% p=0.001

0% 0%
0 +24 h +48 h +72 h +24 h +48 h

Boersma E, et al. Circulation. 1999;100:2045-2048.

PCI
In-hospital Mortality is Lower With Early
GP IIb/IIIa Inhibitor Use (within 24 hrs) †
8%

∆ 42%
No early p<0.0001

In-hospital mortality (%)

6%
GP IIb/IIIa inhibitor
(n=26,596) 4.59%

Early GP IIb/IIIa 4%
inhibitor (n=14,296)
2.59%

2%

0%

Includes patients who received late GP IIb/IIIa inhibitor (> 24 hrs) therapy.
† Unadjusted for risk.
 TIMI Risk Score for UA/NSTEMI:
7 Independent Predictors
– Aged ≥65 years
– ≥3 CAD risk factors
– Prior CAD (stenosis >50%)
– Aspirin in last 7 days
– >2 anginal events in
≤24 hours
– ST deviation
– Elevated cardiac markers
(CK-MB or troponin)
TIMI, thrombosis in myocardial infarction; UA, unstable angina; NSTEMI, non–ST-segment elevation
myocardial infarction; CAD, coronary artery disease.
Antman EM, et al. JAMA. 2000;284:835-842.
 TIMI risk score predicts 30 day mortality after a myocardial infarction

                                                                              

The TIMI risk score has a continuous association with 30-day mortality in patients with an ST elevation
(STE) myocardial infarction who are eligible for fibrinolytic therapy.

Morrow, DA, Antman, EM, Charlesworth, A, et al Circulation 2000; 102:2031.

TIMI risk score predicts 14 day outcome for NSTEMI and UA
                                                                             

The TIMI risk score has a continuous association with 14-day mortality, recurrent MI and target vessel
revascularization in patients with an NSTEMI and unstable angina (UA)
Antman, EM, Cohen, et al, JAMA 2000; 284:835.
STRIVE TM
STRIVE TM
STRIVE TM
 Chest Pain
Classification/Triage

Class I
Class II
Class III
Class IV
Class V
Class “x”
 Class I

• STEMI
Chest pain with STE or new LBBB

• Acute revascularization followed by

CICU admission
 Class II
• Unstable Angina/NSTEMI (high risk)
– Positive initial cardiac markers
– ST depression > 1mm in two contiguous leads
– TIMI risk score > 5
– Continued angina requiring IV NTG drip
– CHF
– SBP < 90mmHg or > 180mmHg
– New mitral regurgitaiton
– Recent ACS (< 30 days)

• Admit to CICU by cardiology

 Class III
• Unstable Angina
– No initial increase in cardiac markers
– Normal ECG or ST depression < 1mm
– No CHF
– No recent ACS
– TIMI risk score 3-4

• Admit to telemetry by cardiology

 Class IV
• Unstable Angina with normal ECG
– No initial increase in cardiac markers
– No history of CAD
– TIMI risk score < 3
– No ongoing or recurring pain

• Admit to Chest Pain Service or Chest

Pain Center in ER
 Class V

• Non-cardiac Chest Pain

• Workup in ER with appropriate referral

 Class “x”

• Critical causes of acute chest pain

other than ACS or ACS combined with
other acute critical/life-threatening
illnesses

• Admit to intensive care (MICU, SICU or

CICU) as appropriate
Chest pain algorithm