Acute Coronary Syndromes

Unstable Angina/Non Q-Wave MI

Current Management Concepts
David Putnam, MD
Albany Medical College

Spectrum of Acute Coronary

Syndromes
Stable
Unstable
Non-Q

Angina

Angina

wave MI

Non ST
Elevation ACS

Q wave
MI

ST Elevation
MI

ECG - ST
ECG - ST

CK-MB
Troponin
CRP
Cannon CP. 1999

Acute Coronary Syndromes (ACS)

Van de Werf F. Throm Haemost. 1997; 78(1):210-213.

Presentation for Acute Coronary Syndromes

in US Emergency Departments
8.0 MM ED visits annually for
urgent chest pain1
6.1 MM non-ACS

ST segment > 1.0mm, or

New left bundle branch
block

569 M for
ST-segment elevation MI
(ST MI)2

1. Personal communication, W.Brian Gibler, MD, University of Cincinnati.

2. 1997 hospital discharge survey, 1997 SMG HPD database.

ST segment > 0.5mm, or

T wave inversion > 1mm, or
ST segment 0.5mm- 1.0mm

- Cardiac enzymes

+ Cardiac enzymes

1,048 M for
unstable angina
(UA)2

302 M for
non-Q-wave MI
(NQMI)2

Acute Coronary Syndromes

Unstable angina is a clinical syndrome

falling between chronic angina pectoris

and myocardial infarction in the spectrum
of patients with coronary artery disease
(CAD)
Non Q-wave MI is a clinical syndrome
falling between unstable angina and Qwave MI

Unstable Angina

Chest pain syndrome, either new onset or

progressive angina
Transient ST-segment depression on the
electrocardiogram (ECG)
Without evidence of myocardial infarction
by CK, CK-MB, or Troponin

Non Q-Wave MI

Chest pain syndrome, either new onset or

progressive angina
Transient or persistent ST-segment
depression on the electrocardiogram
(ECG)
With evidence of myocardial infarction by
CK, CK-MB, or Troponin

Unstable Angina/NQWMI

Significant likelihood of occurrence of

major cardiac events
A. Incidence of MI: 8 to 10%
B. Mortality: 2 to 5%

6-month mortality for UA/NQMI and ST MI

10%
ST ACS

% 8%
Cumulative
mortality
at 6 months 6%

ST MI
with
fibrinolytics

4%

T-wave
inversion

2%
0%
0

30

60

90

120

Days from randomization

Granger CB et al. J Am Coll Cardiol. 1998; 31:79A.

150

180

Unstable Angina/NQWMI:
Pathophysiology

Acute plaque fissuring and rupture

Superimposed thrombus
Transient occlusion
Mediator-induced vasospasm may be
present

Pathophysiology of UA/NQMI

White HD. Am J Cardiol. 1997; 80 (4A): 2B-10B.

Small, vulnerable plaques are

responsible for causing MI
60

68%

MI
Patients 40
(%)
20
0

<50%

Falk et al: Circulation 1995;92:657671

18%

14%

50%70%

>70%

% Stenosis

Determinants of Plaque Vulnerability

Lipid-rich core size

Cap thickness
Cap inflammation and repair

Unstable Angina
Clinical Presentation

Rest angina within 1 week of presentation

New onset angina of CCSC (Canadian)

Class III or IV within 2 months of

presentation
Angina increasing in CCSC Class to at
least Class III or IV
Non-Q-wave myocardial infarction
Post-MI angina (>24 hours)

Angina
Canadian Cardiovascular Classification

Class I
Class II
Class III
Class IV

Prolonged exertion
Walking >2 blocks
Walking >1 block
Minimal or rest

Campeau L. Circulation 1976;54:522-23

Unstable Angina/NQWMI
Initial Evaluation

Should take place in a medical facility, not

by telephone
Careful clinical history
Physical examination
Assessment of likelihood of coronary
artery disease
Assessment of risk of adverse outcomes

Evaluation in Emergency Department

History
Physical
ECG ( serial ECGs if indicated )
CK-MB, Troponin

Evaluation in Emergency Dept

Time goal of initial assessment and triage

to be completed is 10 minutes

Common Symptom History in

Acute Coronary Syndromes
Chest Pain
Usually substernal
Crushing or squeezing in quality
Can resemble indigestion
May radiate to either arm, neck, jaw,
epigastrium, or between scapulae
Generally under 20 minutes in duration with
unstable angina but may be longer with NQWMI

Associated Symptoms in
Unstable Angina/NQWMI

Dyspnea
Diaphoresis
Weakness
Nausea
Vomiting
Feeling of impending doom

Common Cardiac Causes of Chest Pain

Angina
Myocardial Infarction
Aortic valve disease
Hypertrophic or congestive cardiomyopathy
Aortic dissection
Pericarditis
Mitral valve prolapse

Noncardiovascular Causes of
Chest Pain

Abnormalities of the cervicodorsal spine

Costochondral separation
Nonspecific chest wall pain
Gastrointestinal disease: indigestion, hiatal

hernia, GERD, esophagitis

Dyspnea
Pleuritic pain secondary to pleural
effusion/pneumonia

Physical Examinaton

Not that helpful

May have evidence of CHF:

JVD, rales,

edema
May have S4
May have murmur of mitral regurgitation
from papillary muscle dysfunction

Electrocardiogram

One of the most important tests that can be

performed is the twelve-lead ECG taken

during chest pain
In the absence of ECG changes during
chest pain, the diagnosis of myocardial
ischemia is unlikely

Coronary Markers

CK-MB Levels

9461 patients in the PURSUIT Trial

CK-MB elevation directly correlated with

mortality
Increased risk begins with CK-MB
elevations just above normal levels

JAMA 2000;283:347-353

Troponin T and Troponin I

773 patients with chest pain less than 12 hours and

without ST elevation
Testing on arrival and six hours after onset of pain
Event rates in patients with negative tests were
1.1% for Troponin T and 0.3% for Troponin I

NEJM 1997;337:1648-53

TIMI 11B

Results

cTnI SUBSTUDY

Clinical events at 14 days (%)

30
25

Baseline cTnI and Outcomes by 14 Days

P < 0.00001

cTnI < 0.1 ng/ml

cTnI >= 0.1 ng/ml

22.4
P = 0.0008

20
15
10
5

14

P = 0.005
P = 0.04

4.2
1.3

7.9

8.5
5.5

2.5

Death

MI

UR

D/MI/UR

Acute Coronary Syndrome

I n it ia l H is t o r y T y p e
and E C G
E s t im a t e
L ik e lih o o d o f C A D

E s t im a t e R is k o f
D e a th o r M I

Likelihood of CAD

Likelihood of Adverse Events

Practical Point of View

Patients to Admit

Patients with symptoms within 24 hours of

presentation
Angina with increased frequency, severity,
and/or duration
New onset of prolonged rest angina
Recurrent angina after a recent MI

Unstable Angina
Outpatient Care

Patients at low risk for adverse outcomes

Onset or worsening of symptoms within

preceeding two weeks but without severe,

prolonged, or rest episodes
Follow-up evaluation within 72 hours

Unstable Angina
Outpatient Care
Medical Management
Aspirin 80-324 mg/day
Ticlodipine 250 mg bid or Clopidogrel mg
qd ( patients unable to take Aspirin )
Sublingual NTG prn
Oral beta blockers and/or long-acting
topical or oral nitrates

Acute Coronary Syndromes

Acute Coronary Syndromes

Potential First Line Drugs

Beta-blocker
Nitrates
Aspirin
2b3a Inhibitors
Heparin

Initial Medical Treatment

Choice/timing of drugs determined by:
Certainty of diagnosis
Severity of symptoms
Hemodynamic state
Medication history

Beta Blockers

Decrease frequency and duration of

myocardial ischemia
Decrease development of refractory angina
Decrease mortality and incidence of
myocardial infarction
Intravenous forms recommended in unstable
situations

Beta Blockers

Remain the mainstay of therapy in patients

with acute ischemic syndromes

Should be used in all patients unless
contraindicated

Beta Blockers:
Contraindications

Acute bronchospasm
History of severe COPD or severe asthma
Significant bradycardia ( < 60 )
Significant hypotension ( SBP < 90 )
Overt CHF

Nitrates

Decrease frequency and duration of

myocardial ischemia
Decrease development of refractory angina
No reduction in mortality or incidence of
myocardial infarction
Intravenous forms recommended in
unstable situations
Tolerance may develop quickly

Unstable Angina
Calcium Channel Blockers

Are not first-line therapy

May be used as add-on therapy
Rate limiting calcium channel blockers

may be used as substitute for beta blocker

if beta blocker contraindicated

 Anti-Platelet/Anti-Thrombin Therapy

Acute Ischemic Syndromes

Aspirin

Reduces risk of fatal/nonfatal MI

A. 71% during acute phase

B. 60% at 3 months
C. 52% at 2 years
Reduces risk of early and late major
complications

Aspirin--Platelet Inhibition

Potent inhibitor of arachidonic acid

Weak inhibitor of ADP, thrombin
Does not prevent alpha granule release
Does not inhibit shear-induced platelet
aggregation

Outcomes with aspirin plus heparin in UA/NQMI

TIMI IIIb1
42 Days

ESSENCE2
30 Days

FRISC3
40 Days

GUSTO IIb4 PRISM-PLUS5 PURSUIT6

30 Days
30 Days
30 Days

% death or
MI

15.7%
11.9%
8.8%

7.7%

8.0%

9.1%

(n=744)
(n=1,564)
(n=755)
(n=3,994) (n=797)
(n=4,739)
4. GUSTO IIb Investigators. N Engl J Med. 1996; 335: 775-782.
1. The TIMI IIIb investigators. Circulation. 1994; 89 (4): 1545-1556.
2. Cohen M et al. N Engl J Med. 1997; 337 (7): 447-452.
3. FRISC study group. Lancet. 1996; 347: 561-568.

5. The PRISM-PLUS investigators. N Engl J Med. 1998; 338: 1488-1497.

6. PURSUIT investigators N Engl J Med. 1998; 339: 436-443.

Unstable Angina: Aspirin

Stat Aspirin 324 mg chewed then 162 to

324 mg/day
Clopidogrel 75 mg po if Aspirin intolerant
or already on aspirin

Mechanism of action for GP IIb-IIIa inhibitors

White HD. Am J Cardiol. 1997; 80 (4A): 2B-10B.

Mechanism of action for GP IIb-IIIa inhibitors

White HD. Am J Cardiol. 1997; 80(4A):2B-10B.

Unstable Angina: IIb/IIIa Inhibitors

2b3a Inhibitors
Small Molecular Weight Compounds

Tirofiban

(Aggrastat)
Eptifibatide
(Integrilin)

No binding to 2b/3a

receptor (competative
inhibitor)
High plasma
concentration
Short half life

2b3a Inhibitors
Large Molecular Weight Compounds

Abciximab
(Reopro)

Binds to the 2b/3a

receptor directly
Low plasma
concentration
Long half life

Unstable Angina: IIb/IIIa Inhibitors

Contraindications

History of bleeding diathesis

Evidence of active abnormal bleeding

within previous 30 days

Severe hypertension (SBP>200,
DBP>110)
Major surgery within past 6 weeks

Unstable Angina: IIb/IIIa Inhibitors

Contraindications

History of stroke within 30 days

History of hemorrhagic stroke
Platelet count < 100,000
Serum creatinine > 2.0 (eptifibatide)
Dependency on renal dialysis
(eptifibatide)

Unstable Angina: IIb/IIIa Inhibitors

Indications

Positive troponin
Marked ST segment depression
Status-post recent MI
Currently on Aspirin

Heparin

Reduction in frequency and duration of

ischemic episodes
Reduction in MI
Reduction in MI/mortality when combined
with Aspirin
Potential to reduce complications and
improve survival in PTCA

Unstable Angina
Heparin vs. ASA

Double-blind, randomized trial

484 patients

A. 240 patients treated with IV heparin

B. 244 patients treated with aspirin
MI occurrence
A. 0.8% of patients treated with heparin
B. 3.7% of patients treated with aspirin
Theroux P. CIRCULATION 1993;88:2045-8

Unstable Angina
Heparin

Should be used in intermediate and high

risk patients for its antithrombin effect

Low molecular weight heparin is probably
better than unfractionated heparin
How long patients should be treated with
heparin is not clear (probably should
maintain for at least 48 hours)

Unstable Angina
Low Molecular Weight Heparin

Meta-analysis of TIMI 11b and ESSENCE

Enoxaparin superior to unfractionated

heparin
Eight day death/cardiac event rate on
enoxaparin 18.1%
Eight day death/cardiac event rate on
heparin 20.2%
ACC Meeting Mar/99

LMWH vs. Unfractionated Heparin

Review of 12 trials
No convincing diffeerence in effectiveness
between the two drugs.

Lancet 2000(Jun);355;1936-42.

LMWH vs. Unfractionated Heparin

Thrombolytics

Standard treatment regimens have no

demonstrated benefit in unstable angina or

NQWMI

Re-Assessing Persistent Symptoms

Most patients are stabilized/improved after

30 minutes of aggressive medical

management
Patients failing to respond to initial RX
A. Consider other diagnosis
B. Consider early cardiac catheterization
if ongoing ischemia is suspected

Nonintensive Medical Management

Recurrence of pain and return to intensive

management
Noninvasive testing
Cardiac catheterization
Myocardial revascularization
Invasive vs. noninvasive approach
Hospital discharge

Progression to Non-Intensive
Medical Management

Serial enzymes to rule out MI

Follow up ECG at 24 hours
Chest x-ray within 48 hours in stable

patients
Reassess heparin use
Continue Aspirin and oral antianginal
agents

Non-Invasive Testing
Goals

Estimate subsequent prognosis

Determine additional tests and adjustments

in therapy
Determine exercise limitations

Non-Invasive Risk Stratification

Baseline ECG
Continuous ECG monitoring/telemetry
Exercise testing
Myocardial imaging

Baseline ECG

Development of changes with or without

chest pain has important prognostic

implications
ST depression portends a worse prognosis
and is a marker of severe multi-vessel or
left main disease

Exercise Testing

Provides some important prognostic

information
Large disparities in event rates, clinical
classification, and documentation of CAD
Patients with a negative test also appear to
have a high incidence of adverse events

Exercise Testing
Testing Modalities

Exercise Stress Test

Nuclear Stress Test
Persantine Nuclear Stress Test
Dobutamine Nuclear Stress Test
Stress Echocardiogram
Dobutamine Stress Echocardiogram

Choice of Stress Testing Modality

Evaluation of patients resting ECG

Ability to perform exercise
Local expertise and technologies available

Cardiac Catheterization
Goal of cardiac catheterization in patients
with acute coronary syndromes
Provide detailed structural information
Assess prognosis
Select an appropriate long, or short-term
management strategy

Interventional Therapy

Unstable angina often associated with

multi-vessel disease
Wide variation in apparent need for
intervention
Most effective role has not been fully
defined

Early Invasive Strategy vs.

Early Conservative Strategy

Early Invasive Strategy

A. All patients catheterized within 48
hours of admission
Early Conservative Strategy
A. Only high risk patients and patients
with ongoing ischemia receive
a
cardiac catheterization

Early Invasive Strategy vs.

Early Conservative Strategy

Studies Supporting Invasive Strategy

A. FRISCH II
B. TACTICS-TIMI 18
Studies Supporting Conservative Strategy
A. TIMI IIIB
B. VANQWISH

FRISCH II

Invasive Strategy
High-Risk Characteristics

Ongoing resting pain

ECG changes
Positive Troponin
Provacable ischemia

Brigham and Womens Hospital

Critical Pathways for ACS
C r it ic a l P a t h w a y s
fo r A c u t e C o r o n a r y S y n d r o m e s
S T -S e g m e n t
E le v a t io n
T h r o m b o ly s is
P ro to c o l

S T - o r T -W a v e
C hanges

No ECG
C hanges

P r im a r y P T C A
P ro to c o l

A c u t e I s c h e m ia
P ro to c o l

6 -h r R /O M I
P ro to c o l

D o o r t o N e e d le < 3 0 m in u t e s
D o o r t o B a llo o n < 6 0 m in u t e s
A p p r o p t r ia t e M e d s
R is k S t r a t ific a t io n

R e lie f o f I s c h e m ia
R a p id T r ia g e
A p p r o p r ia t e M e d s
In v o r C o n s e rv R x

R a p id R / O M I
EST
E a r ly D is c h a r g e
A p p r o p r ia t e F o llo w - u p

Critical Pathways for ACS

Acute Ischemia Protocol
A s p ir in
C o n s id e r 2 b 3 a
I n h ib it o r

H e p a r in

B e t a B lo c k e r
N it r a t e s
C a lc iu m C h a n n e l B lo c k e r s
(A d d -o n T h e ra p y )

C o n s id e r C a r d ia c C a t h

The End

Clinical manifestations of arterial thrombosis

ST MI:

UA/NQMI:

occlusive thrombus (platelets,

red blood cells, and fibrin)

Partially-occlusive thrombus
(primarily platelets)

Intra-plaque
thrombus (platelet
dominated)

Plaque core

Adapted from Davies MJ. Circulation. 1990; 82 (supl II): 30-46.

Intra-plaque
thrombus (platelet dominated)

SUDDEN DEATH

Plaque core