Transcript Slide 1

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
Coronary Plaques
Platelets
ACS=acute coronary syndrome.
UA=unstable angina.
Bhatt DL. J Invasive Cardiol. 2003;15:3B-9B.
Vascular
Inflammation
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
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
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
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
*Aspirin was the predominant antiplatelet agent studied
**Vascular events include MI, stroke, or death
Antithrombotic Trialist Collaboration. BMJ 2002;324:71–86.
0.0
0.5
1.0
1.5
2.0
Antiplatelet better Control better
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
Mechanism of action of nitrates
B
b-blocker Recommendations
b-blocker Recommendations
I IIa IIb III
Start and continue indefinitely in all post MI, ACS, LV
dysfunction with or without HF symptoms, unless
contraindicated.
I IIa IIb III
Consider chronic therapy for all other patients with
coronary or other vascular disease or diabetes unless
contraindicated.
*Precautions but still indicated include mild to moderate asthma or chronic obstructive pulmonary
disease, insulin dependent diabetes mellitus, severe peripheral arterial disease, and a PR
interval >0.24 seconds.
MI=Myocardial infarction, HF=Heart Failure
b-blocker Evidence
Summary of Secondary Prevention Trials of b-blocker Therapy
Total #
Patients
RR (95% CI)
Acute
treatment
28,970
0.87 (0.77-0.98)
Secondary
prevention
24,298
0.77 (0.70-0.84)
Overall
53,268
0.81 (0.75-0.87)
Phase of
Treatment
0.5
CI=Confidence interval, RR=Relative risk
1.0
RR of death
b-blocker
Placebo
better
better
2.0
Antman E, Braunwald E. Acute Myocardial Infarction. In: Braunwald E, Zipes DP, Libby P, eds. Heart
Disease: A textbook of Cardiovascular Medicine, 6th ed., Philadelphia, PA: W.B. Sanders, 2001, 1168.
b-blocker Evidence: Post MI with
Left Ventricular Dysfunction
Proportion Event-free
Carvedilol Post-Infarct Survival Control in LV Dysfunction (CAPRICORN)
6,644 patients with LVEF <0.40 after a MI with or without HF randomized to
carvedilol or placebo for 24 months
1
0.95
n=975
0.9
Carvedilol
n=984
0.85
0.8
0.75
0.7
RR 0.77 P=.03
0
0.5
1
1.5
Years
The CAPRICORN Investigators. Lancet. 2001;357:1385–1390.
Placebo
2
2.5
b-blocker Evidence: Benefit in HF and LVSD
Study
Drug
HF
Severity
Patients
(n)
Follow-up
(years)
Mean
Dosage
Effects on Outcomes
CIBIS
Bisoprolol*
ModerateSevere
641
1.9
3.8
mg/day
All cause mortality
22% (p=NS)
CIBIS-II
Bisoprolol*
ModerateSevere
2,647
1.3
7.5
mg/day
All cause mortality
34% (P<0.0001)
BEST
Bucindolol*
ModerateSevere
2,708
2.0
152
mg/day
All cause mortality
10% (p=NS)
MERIT-HF
Metoprolol
succinate#
MildModerate
3,991
1.0
159
mg/day
All cause mortality
34% (P=0.0062)
MDC
Metprolol
tartrate*
MildModerate
383
1.0
108
mg/day
Death or Need for Tx
30% (P=NS)
CAPRICORN
Carvedilol
Mild
1,989
1.3
40
mg/day
All cause mortality
23% (P =0.03)
US Carvedilol
Carvedilol
MildModerate
1,094
0.5
45
mg/day
All-cause mortality†
65% (P=.0001)
COPERNICUS
Carvedilol
Severe
2,289
0.9
37
mg/day
All-cause mortality
35% (P =0.0014)
*Not an approved indication
†Not a planned end point.
#Not approved for severe HF or mortality reduction alone
Blood Pressure Control Recommendations
Goal: <140/90 mm Hg or <130/80 if
diabetes or chronic kidney disease
I IIa IIb III
I IIa IIb III
Blood pressure 120/80 mm Hg or greater:
Initiate or maintain lifestyle modification: weight control,
increased physical activity, alcohol moderation, sodium
reduction, and increased consumption of fresh fruits vegetables
and low fat dairy products
Blood pressure 140/90 mm Hg or greater (or 130/80 or
greater for chronic kidney disease or diabetes)
As tolerated, add blood pressure medication, treating initially
with beta blockers and/or ACE inhibitors with addition of other
drugs such as thiazides as needed to achieve goal blood
pressure
Blood Pressure: Lower is Better
Age at Risk (Y)
80-89
256
128
70-79
64
60-69
32
50-59
16
40-49
8
4
2
1
0
120
140
160
180
Usual Systolic BP (mm Hg)
BP=Blood pressure
Prospective Studies Collaboration. Lancet. 2002;360:1903-1913
Ischemic Heart Disease Mortality
Ischemic Heart Disease Mortality
Ischemic Heart Disease Mortality
Age at Risk (Y)
80-89
256
128
70-79
64
60-69
32
50-59
16
40-49
8
4
2
1
0
70
80
90
100 110
Usual Diastolic BP (mm Hg)
Blood Pressure: Risk of CHD with Active Treatment
Veterans Administration, 1967
Veterans Administration, 1970
Hypertension Stroke Study, 1974
USPHS Study, 1977
EWPHE Study, 1985
Coope and Warrender, 1986
SHEP Study, 1991
STOP-Hypertension Study, 1991
MRC Study, 1992
Syst-Eur Study, 1997
0.79
(0.69 to 0.90)
Total 0
CHD=Coronary heart disease
He J et al. Am Heart J 1999; 138:211-219
0.5
1.0
1.5
2.0
Better than placebo Worse than placebo
JNC VII Guidelines for Management and Treatment
SBP*
mmHg
DBP*
mmHg
Lifestyle
modification
<120
<80
Encourage
Prehypertension
120–139
80–89
Yes
Stage 1
Hypertension
140–159
90–99
Yes
>100
Yes
BP classification
Normal
Stage 2
Hypertension
>160
Initial drug therapy
With compelling
indications
Drug(s) for compelling
indications. ‡
Drug(s) for the
compelling indications.‡
Other antihypertensive
drugs (diuretics, ACEI,
ARB, BB, CCB) as
needed.
ACEI=Angiotensin converting enzyme inhibitor, ARB=Angiotensin receptor blocker, BB=b-blocker, BP=Blood pressure,
CCB=Calcium channel blocker, DBP=Diastolic blood pressure, SBP=Systolic blood pressure
*Treatment determined by highest blood pressure category. †Initial combined therapy should be used cautiously in those at
risk for orthostatic hypotension.
‡Treat patients with chronic kidney disease or diabetes mellitus to blood pressure goal of <130/80 mmHg.
Chobanian AV et al. JAMA. 2003;289:2560-2572
JNC VII Lifestyle Modifications for BP Control
Modification
Recommendation
Approximate SBP
Reduction Range
Maintain normal body weight (BMI=18.524.9)
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
JNC VII Compelling Indications for Drug Classes
Compelling Indication
Initial Therapy Options
Clinical-Trial Basis
Heart Failure
Diuretic, BB, ACEI,
ARB, Aldo Ant
MERIT-HF, COPERNICUS, CIBIS,
SOLVD, AIRE, TRACE, Val-HeFT,
RALES
Post-MI
BB, ACEI, Aldo Ant
ACC/AHA Post-MI Guideline, BHAT,
SAVE, Capricorn, EPHESUS
High CAD Risk
Diuretic, BB, ACEI, CCB
ALLHAT, HOPE, ANBP2,
LIFE, CONVINCE
Diabetes Mellitus
Diuretic, BB, ACEI,
ARB, CCB
Chronic Kidney Disease
ACEI, ARB
Recurrent Stroke Prevention
Diuretic, ACEI
NKF-ADA Guideline,
UKPDS, ALLHAT
NKF Guideline, Captopril Trial,
RENAAL, IDNT, REIN, AASK
PROGRESS
ACEI=Angiotensin converting enzyme inhibitor, Aldo Ant=Aldosterone antagonist, ARB=Angiotensin receptor blocker,
BB=b-blocker, CAD=Coronary artery disease, CCB=Calcium channel blocker, MI=Myocardial Infarction
Chobanian AV et al. JAMA. 2003;289:2560-2572
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*
RR (95% Cl)
Study
Aberg, et al. 1983
0.67 (0.53-0.84)
Herlitz, et al. 1995
0.99 (0.42-2.33)
Johansson, et al. 1985
0.79
Perkins, et al. 1985
3.87 (0.81-18.37)
Sato, et al. 1992
0.10 (0.00-1.95)
Sparrow, et al. 1978
0.76 (0.37-1.58)
Vlietstra, et al. 1986
0.63 (0.51-0.78)
Voors, et al. 1996
0.54 (0.29-1.01)
0.1
Ceased smoking
*Includes those with known coronary heart disease
Critchley JA et al. JAMA. 2003;290:86-97.
1.0
Continued smoking
10
CI=Confidence interval, RR=Relative risk
(0.46-1.37)
Lipid Management Goals: NCEP
Risk Category
High risk:
CHD or CHD risk equivalents
(10-year risk >20%)
and
Very high risk:
ACS or established CHD
plus: multiple major risk
factors (especially diabetes) or
severe and poorly controlled
risk factors
Consider
Drug Therapy
LDL-C and non-HDLC Goal
Initiate TLC
<100 mg/dL
if TG > 200 mg/dL,
non-HDL-C should
be < 130 mg/dL
100 mg/dL
>100 mg/dL
(<100 mg/dL: consider drug
options)
<70 mg/dL,
non-HDL-C < 100
mg/dL
All patients
>100 mg/dL
(<100 mg/dL: consider drug
options)
ATP=Adult Treatment Panel, CHD=Coronary heart disease, LDL-C=Low-density lipoprotein cholesterol,
TLC=Therapeutic lifestyle changes
Grundy, S. et al. Circulation 2004;110:227-39.
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
drug therapy
I IIa IIb III
I IIa IIb III
If on-treatment LDL-C > 100 mg/dL, intensify LDLlowering drug therapy (may require LDL lowering drug
combination)
If baseline is LDL-C 70 to 100 mg/dL, it is reasonable to
treat to LDL < 70 mg/dL
When LDL lowering medications are used, obtain at least a 30-40% reduction in LDL-C
levels.
Lipid Management Recommendations
I IIa IIb III
If TG are 200-499 mg/dL, non-HDL-C should be < 130
mg/dL
I IIa IIb III
Further reduction of non-HDL to < 100 mg/dL is reasonable
I IIa IIb III
Therapeutic options to reduce non-HDL-C:
More intense LDL-C lowering therapy I (B) or
Niacin (after LDL-C lowering therapy) IIa (B) or
Fibrate (after LDL-C lowering therapy) IIa (B)
If TG are > 500 mg/dL, therapeutic options to prevent
pancreatitis are fibrate or niacin before LDL lowering
therapy; and treat LDL-C to goal after TG-lowering therapy.
Achieve non-HDL-C < 130 mg/dL, if possible
HMG-CoA Reductase Inhibitor: Secondary Prevention
Heart Protection Study (HPS)
20,536 patients with CAD, other occlusive arterial disease, or DM
randomized to simvastatin (40 mg) or placebo for 5.5 years
Event Rate Ratio (95% CI)
Baseline
LDL-C (mg/dL)
Statin
(n = 10,269)
Placebo
(n = 10,267)
<100
282 (16.4%)
358 (21.0%)
100–129
668 (18.9%)
871 (24.7%)
130
1083 (21.6%)
1356 (26.9%)
All patients
2033 (19.8%)
2585 (25.2%)
Statin Better
Statin Worse
0.76 (0.72–0.81)
P<0.0001
0.4
CAD=Coronary artery disease, CI=Confidence interval, DM=Diabetes mellitus,
HPS Collaborative Group. Lancet 2002;360:7-22
0.6
0.8
1.0
1.2
1.4
HMG-CoA Reductase Inhibitor: Secondary Prevention
Recurrent MI or
Cardiac Death
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
Pravastatin
25
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
Statin
30
4S
Placebo
Event (%)
25
4S
20
LIPID
15
LIPID
CARE
10
HPS
5
0
CARE
HPS
TNT (atorvastatin 10 mg/d)
TNT (atorvastatin 80 mg/d)
0
70
90
110
130
150
LDL-C (mg/dL)
170
190
210
LDL-C=Low density lipoprotein cholesterol; TNT=Treating to New Targets; HPS=Heart Protection Study;
CARE=Cholesterol and Recurrent Events Trial; LIPID=Long-term Intervention with Pravastatin in Ischaemic Disease;
4S=Scandinavian Simvastatin Survival Study.
LaRosa JC et al. NEJM. 2005;352:1425-1435
Lipid Management Pharmacotherapy
TC
LDL
HDL
TG
Patient
tolerability
 19-37%
 25-50%
4-12%
 14-29%
Good
 13%
18%
1%
 9%
Good
Bile acid
sequestrants
7-10%
10-18%
3%
Neutral or
Poor
Nicotinic acid
 10-20%
 10-20%
14-35%
 30-70%
Reasonable to
Poor
19%
4-21%
11-13%
30%
Good
Therapy
Statins*
Ezetimibe
Fibrates
HDL-C=High-density lipoprotein cholesterol, LDL-C=Low-density lipoprotein cholesterol,
TC=Total cholesterol, TG=Triglycerides
*Daily dose of 40mg of each drug, excluding rosuvastatin.
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
Saturated fat*
Recommended Intake
<7% of total calories
Polyunsaturated fat
Up to 10% of total calories
Monounsaturated fat
Up to 20% of total calories
Total fat
25%–35% of total calories
Carbohydrate (esp. complex carbs)
Fiber
50%–60% of total calories
20–30 g/d
Protein
Cholesterol
~15% of total calories
<200 mg/d
*Trans fatty acids also raise LDL-C and should be kept at a low intake.
Note: Regarding total calories, balance energy intake and expenditure to maintain
desirable body weight.
ATP=Adult Treatment Panel
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.
Weight Management Recommendations
I IIa IIb III
Goal: BMI 18.5 to 24.9 kg/m2
Waist Circumference: Men: < 40 inches
Women: < 35 inches
Assess BMI and/or waist circumference on each visit and
consistently encourage weight maintenance/
reduction through an appropriate balance of physical activity,
caloric intake, and formal behavioral programs when indicated.
I IIa IIb III
I IIa IIb III
If waist circumference (measured at the iliac crest) >35 inches in
women and >40 inches in men initiate lifestyle changes and
consider treatment strategies for metabolic syndrome as
indicated.
The initial goal of weight loss therapy should be to reduce body
weight by approximately 10 percent from baseline. With success,
further weight loss can be attempted if indicated.
*BMI is calculated as the weight in kilograms divided by the body surface area in meters2.
Overweight state is defined by BMI=25-30 kg/m2. Obesity is defined by a BMI >30 kg/m2.
CV Risk Increases with Body Mass Index
Hazard Ratio
Hemorrhagic
Stroke
Ischemic
Stroke
Ischemic Heart
Disease
4.0
4.0
4.0
2.0
2.0
2.0
1.0
1.0
1.0
0.5
0.5
0.5
16 20 24 28 32 36
CV=Cardiovascular
16 20 24 28 32 36
Body Mass Index (kg/m2)*
Body mass index is calculated as the weight in kilograms divided by the
body surface area in meters2.
Mhurchu N et al. Int J Epidemiol 2004;33:751-758
16 20 24 28 32 36
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)
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
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
I IIa IIb III
Goal: 30 minutes 7 days/week,
minimum 5 days/week
Assess risk with a physical activity history and/or an exercise
test, to guide prescription
I IIa IIb III
Encourage 30 to 60 minutes of moderate intensity aerobic
activity such as brisk walking, on most, preferably all, days of
the week, supplemented by an increase in daily lifestyle
activities
I IIa IIb III
Advise medically supervised programs for high-risk patients
(e.g. recent acute coronary syndrome or revascularization,
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
Qu i c k T i m e ™ a n d a
T I F F (U n c o m p re s s e d ) d e c o m p re s s o r
a re n e e d e d to s e e t h i s p i c t u re .
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
chest pain
Clinical finding
Atypical
pain
EKG
Serum markers
Risk assessment
Diagnostic
rule out MI/ACS
pathway
Negative
UA
NSTEMI
Exertional
pain
Rest pain, Post-MI,
DM, Prior Aspirin
Ongoing
pain
Negative
ST-T wave
changes
ST
elevation
Negative
Low
probability
Low
risk
Positive
Medium-high
risk
Aspirin, heparin/low-molecularweight heparin (LMWH) +
clopidogrel
Anti-ischemic Rx
Early conservative therapy
Discharge
DM=diabetes mellitus.
Cannon, Braunwald. Heart Disease. 2001.
STEMI
Stable
angina
STEMI
Thrombolysis
Primary PCI
Aspirin + GP IIb/IIIa inhibitor
clopidogrel + heparin/
LMWH + anti-ischemic Rx
Early invasive Rx
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
• b-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
cascade
Platelets
Collagen
Leukocytes
LMWH
Platelets
Tissue factor
LMWH
UFH
TFPI
Thromboxane A2 vWF ADP
Thienopyridines
Aspirin
Factor Xa
Activated platelets
GP IIb/IIIa
inhibitors
Prothrombin
LMWH
UFH
Fibrinogen cross-linking
Thrombin
Platelet aggregation
Direct
thrombin
inhibitors
Fibrinogen
UFH=unfractionated heparin.
LMWH=low-molecular-weight heparin
ADP=adenosine diphosphate.
TFPI=tissue factor pathway inhibitor
Selwyn A. Am J Cardiol. 2003;91:3H-11H.
Fibrin
Thrombus
Plasmin
Fibrin
degradation
Thrombolytics
Efficacy of Aspirin Doses on Vascular
Events in High Risk Patients
Aspirin Dose
# Trials OR* (%)
500–1500 mg
34
19
160–325 mg
19
26
75–150 mg
12
32
<75 mg
Any aspirin
3
65
13
23
0
Odds Ratio
0.5
Anti - platelet Better
*Odds reduction.
1.0
1.5
Anti - platelet
Worse
Treatment effect P < 0.0001.
Adapted with permission from the BMJ Publishing Group. Anti-thrombotic Trialists’ Collaboration. BMJ.
2002;324:71-86.
2.0
Comparison of Heparin + ASA vs ASA Alone
B
Theroux
B
RISC
B
Cohen 1990
B
ATACS
B
B
Summary Relative Risk
0.67 (0.44-0.1.02)
0.1
Heparin + ASA
55/698=7.9%
Holdright
Gurfinkel
B
1
RR:
Death/MI
10
ASA Alone
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
Death or MI
UFH
(%)
ENOX
(%)
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
Favors
ENOX
OR
(95 CI)
%
Day
1
OR
P
2
Favors
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 halflife, 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
Cumulative Hazard Rate
0.14
Placebo
+ Aspirin*
0.12
20%
Relative-risk
Reduction
0.10
0.08
P<0.001
N=12,562
Clopidogrel
+ Aspirin*
0.06
0.04
0.02
0.00
0
3
6
9
Months of Follow-Up
*Other standard therapies were used as appropriate.
CV=cardiovascular.
CURE Trial Investigators. N Engl J Med. 2001;345:494-502.
12
Early Use of GP IIb/IIIa Inhibition Improves
PCI: CAPTURE, PURSUIT, PRISM-PLUS
Post-PCI
Before PCI
Placebo
GP IIb/IIIa Inhibitor
Death/MI
8%
6%
8.0%
8%
6%
n=12,296
p=0.001
4%
10%
Death/MI
10%
4.3%
4.9%
4%
2.9%
2%
2%
0%
0%
0
+24 h
+48 h
n=2754
p=0.001
+24 h
+72 h
Boersma E, et al. Circulation. 1999;100:2045-2048.
PCI
+48 h
In-hospital Mortality is Lower With Early
GP IIb/IIIa Inhibitor Use (within 24 hrs) †
No early
GP IIb/IIIa inhibitor
(n=26,596)
Early GP IIb/IIIa
inhibitor (n=14,296)
In-hospital mortality (%)
8%
∆ 42%
p<0.0001
6%
4.59%
4%
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