Acute Coronary

Syndrome
Steven R. Bruhl MD, MS
3rd Year Cardiology Fellow
Internal Medicine Didactics
July 14, 2010

Goals and Objectives

Discuss the definition & pathophysiology of

ACS
Recognize the clinical features of low,
intermediate and high risk ACS
Be able to identify and treat patients
appropriate for a conservative or invasive
strategy
Discuss new and controversial
pharmacological treatments

Gold Standard for Treatment of ACS

ACC/AHA 2007 Guidelines for the Management of

Patients With Unstable Angina/NonST-Elevation
Myocardial Infarction

http://circ.ahajournals.org/cgi/content/full/102/10/1193

Algorithm for evaluation and management of patients suspected of having ACS.

Anderson JL, et al. J Am Coll Cardiol 2007;50:e1e157, Figure 2.

ACS Overview

Overview of ACS
Assessment of Likelihood of ACS
Early Risk Stratification
Invasive vs Conservative Strategy
Pharmacotherapy
Long-term Therapy/Secondary Prevention

Scope of the Problem

5 million ER visits nationwide for CP

800,000 experience an MI each year

213,000 die from their event

of those die before reaching the ER

Pre-CCU, mortality for MI was >30%

Fell to 15% with CCU

With current interventions, in hospital mortality of

STEMI is 6-7%

Overview of ACS
Acute Coronary
Syndromes*
1.57 Million Hospital Admissions - ACS
UA/NSTEMI

STEMI

1.24 million

0.33 million

Admissions per year

Admissions per year

*Primary and secondary diagnoses. About 0.57 million NSTEMI and 0.67 million UA.
Heart Disease and Stroke Statistics 2007 Update. Circulation 2007; 115:69171.

Acute Coronary Syndrome (ACS)

Definition: The spectrum of acute ischemia

related syndromes ranging from UA to MI
with or without ST elevation that are
secondary to acute plaque rupture or plaque
erosion.
[----UA---------NSTEMI----------STEMI----]

Pathophysiology of Stable Angina and ACS

Pathophysiology

ACS

Plaque rupture/clot

Increased O2 Demand
O2 supply/demand mismatchIschemia
Myocardial ischemianecrosis

Myocardial Infarction

Anemia

Angina

Flow- limiting stenosis

Asymptomatic

Decreased O2 Supply

Pathophysiology of ACS
Evolution of Coronary Thrombosis

Unstable
Angina
Non
occlusive
thrombus
Non specific
ECG
Normal
cardiac
enzymes

Non-occlusive
NSTEMI
thrombus
sufficient to
cause
tissue damage &
mild
myocardial
necrosis
ST depression
+/T wave inversion
on
ECG
Elevated cardiac
enzymes

STEMI

Complete thromb
occlusion

ST elevations on
ECG or new LBBB
Elevated cardiac
enzymes
More severe
symptoms

STEMI

Name 3 situations in which you cannot

diagnose STEMI

STEMI

Name 3 situations in which you cannot

diagnose STEMI
Left Ventricular Hypertrophy
Chronic or Rate Dependent LBBB
Paced Rhythm

Cardiac Catheterization

Name the only 3 situations that demand

emergent cardiac catheterization.

Cardiac Catheterization

Name the only 3 situations that demand

emergent cardiac catheterization.
STEMI or new LBBB
ACS with hemodynamic or electrical instability
despite optimal medical management
Uncontrolled CP despite optimal medical
management

Diagnosis of ACS

At least 2 of the
following

History ( angina or angina

equivalent)
Acute ischemic ECG changes
Typical rise and fall of cardiac
markers
Absence of another identifiable
etiology

Initial Evaluation and management

of Non ST-elevation ACS
Initial Evaluation and Management
History and Physical
ECG
Cardiac Biomarkers

Establish the Likelihood that

Clinical Presentation
Represents an ACS
Secondary to CAD

Risk Stratify for Short-term

Adverse Outcomes

Likelihood of ACS by Hx/PE

History/Examination

Suggesting AMI

Pain in Chest or Left Arm

CP Radiation
Right Shoulder
Left Arm
Both Left & Right Arm
Diaphoresis
3rd Heart Sound
SBP < 80 mm Hg
Pulmonary Crackles

Panju AA. JAMA. 1998;280:1256.

LR 2.7
LR 2.9 (1.4-6.0)
LR 2.3 (1.7-3.1)
LR 7.1 (3.6-14.2)
LR 2.0 (1.9-2.2)
LR 3.2 (1.6-6.5)
LR 3.1 (1.8-5.2)
LR 2.1 (1.4-3.1)

Likelihood of ACS by Hx/PE

Clinical Examination
Pleuritic Chest Pain
Sharp or Stabbing Pain
Positional Chest Pain
Reproducible Chest Pain

Panju AA. JAMA. 1998;280:1256.

Against AMI
LR 0.2 (0.2-0.3)
LR 0.3 (0.2-0.5)
LR 0.3 (0.2-0.4)
LR 0.2-0.4

Risk Stratification by ECG

Simple, quick, noninvasive tool

Universally available, cheap
Correlates with risk and prognosis
Guides treatment decisions
Can identify alternative causes

Risk Stratification by ECG

ECG Findings and Associated LR for AMI

New ST-E > 1mm

New Q waves
Any ST-E
New Conduction Defect
New ST-D

LR 5.7-53.9
LR 5.3-24.8
LR 11.2 (7.1-17.8)
LR 6.3 ( 2.5-15.7)
LR 3.0-5.2

NORMAL ECG

LR 0.1-0.4

Panju AA. JAMA. 1998;280:1256.

Risk Stratification by ECG

CAVEATS

1-8% AMI have a normal ECG

Only Approx 50% of AMI patients have

diagnostic changes on their initial ECG
Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40.

Risk Stratification by ECG

CAVEATS cont.
1 ECG cannot exclude AMI

Brief sample of a dynamic process

Small regions of ischemia or infarction may be

missed
Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40.

How Sensitive is the ECG Alone?

How Predictive is NTG response?

Timing of Release of Various Biomarkers After

Acute Myocardial Infarction

Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3 rd ed. Rochester, MN: Mayo
Clinic Scientific Press and New York: Informa Healthcare USA, 2007:77380.
Anderson JL, et al. J Am Coll Cardiol 2007;50:e1e157, Figure 5.

Risk Stratification by Troponin

Mortality at 42 Days

%
%

%
%

%
831

174

148

134

50

67

Non ACS causes of Troponin Elevation

1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.

Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac
surgery, after-interventional closure of ASDs)
Congestive heart failure (acute and chronic)
Aortic valve disease and HOCM with significant LVH
Hypertension
Hypotension, often with arrhythmias
Noncardiac surgery
Renal failure
Critically ill patients, especially with diabetes, respiratory failure
Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms)
Hypothyroidism
Coronary vasospasm, including apical ballooning syndrome
Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination,
Post-PCI
Pulmonary embolism, severe pulmonary hypertension
Sepsis
Burns, especially if TBSA greater than 30%
Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma
Acute neurologic disease, including CVA, subarchnoid bleeds
Rhabdomyolysis with cardiac injury
Transplant vasculopathy
Vital exhaustion
Modified from Apple FS, et al Heart J. 2002;144:981-986.

Combined Sensitivities for ACS

Early Invasive

Conservative

Unstable angina/NSTEMI cardiac

care

Evaluate for conservative vs. invasive strategy

based upon:
Likelihood of actual ACS
Risk stratification by

TIMI risk score

ACS risk categories per AHA guidelines
Low

Intermediate

High

TIMI Risk Score

Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days

TIMI Risk Score

T: Troponin elevation (or CK-MB elevation)
H: History or CAD (>50% Stenosis)
R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker)
E: EKG changes: ST elevation or depression 0.5 mm concordant leads
A2:Aspirin use within the past 7 days; Age over 65
T: Two or more episodes of CP within 2 hours

Deciding between Early Invasive vs a Conservative Strategies

Definitive/Possible ACS
Initiate ASA, BB, Nitrates,
Anticoagulants, Telemetry

Early Invasive Strategy

Conservative Strategy

TIMI Risk Score >3Hemodynamic instability

Elecrical instability
New ST segment
Refractory angina
deviation

Positive biomarkers PCI in past 6 months

CABG
EF <40%

TIMI Risk Score <3 (Esp. Women)

No ST segment deviation
Negative Biomarkers

Remains Stable

Coronary angiography
(24-48 hours)

Recurrent Signs/Symptoms

Heart failure
Assess EF and/or Stress Testin

Arrhythmias
EF<40% OR Positive stress
Go to Angiography

Specifics of Early Hospital Care

Anti-Ischemic Therapy
Anti-Platelet Therapy
Anticoagulant Therapy

Early Hospital Care

Anti-Ischemic Therapy

Class I

Bed/Chair rest and Telemetry

Oxygen (maintain saturation >90%)
Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart
failure, hypertension)
Oral B-blockers in First 24-hours if no contraindications.
(IV B-blockers class IIa indication)
Non-dihydropyridine Ca-channel blockers for those with
contraindication fo B-blockers
ACE inhibitors in first 24-hours for heart failure or EF<40%
(Class IIa for all other pts) (ARBs for those intolerant)
Statins

Early Hospital Care

Anti-Ischemic Therapy

Class III

Nitrates if BP<90 mmHg or RV infarction

Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil
Immediate release dihydropyradine Ca-blockers in the
absence of B-Blocker therapy
IV ACE-inhibitors
IV B-blockers in patients with acute HF, Low output state
or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd
degree heart block, active asthma, or reactive airway
disease
NSAIDS and Cox-2 inhibitors

Early Hospital Care

Anti-Platelet Therapy

Class I
Aspirin (162-325 mg), non enteric coated
Clopidogrel for those with Aspirin
allergy/intolerance (300-600 mg load and 75 mg/d)
GI prophylaxis if a Hx of GI bleed
GP IIb/IIIa inhibitors should be evaluated based on
whether an invasive or conservative strategy is used
GP IIb/IIIa inhibitors recommended for all diabetics
and all patient in early invasive arm

Early Hospital Care

Anticoagulant Therapy

Class I
Unfractionated Heparin
Enoxaparin
Bivalarudin
Fondaparinux

Relative choice depends on invasive vs

conservative strategy and bleeding risk

Early Hospital Care

Statin Therapy

MIRACL Trial
Inclusion Criteria
3086 patients with Non ST ACS
Total cholesterol <270 mg/dl
No planned PCI
Randomized to Atorvastatin vs Placebo
Drug started at 24-96 hours

Statin Evidence: MIRACL Study

Primary Efficacy Measure

Placebo
Cumulative Incidence (%)

15

17.4%
14.8%

Atorvastatin
10
Time to first occurrence of:
Death (any cause)
Nonfatal MI
Resuscitated cardiac arrest
Worsening angina with new
objective evidence and
urgent rehospitalization

Relative risk = 0.84

P = .048
95% CI 0.701-0.999

0
0

12

Time Since Randomization (weeks)

Schwartz GG, et al. JAMA. 2001;285:1711-1718.

16

Statin Evidence: MIRACL Study

Fatal and Nonfatal Stroke

Cumulative Incidence (%)

Placebo

1.5

Atorvastatin

0.5

Relative risk = 0.49

P = .04
95% CI 0.24-0.98

0
0

12

16

Time Since Randomization (weeks)

Waters DD, et al. Circulation. 2002;106:1690-1695.

S24

PROVE-IT Trial
All-Cause Death or Major CV Events
in All Randomized Subjects
30

Pravastatin 40mg
(26.3%)

25
20

%
with 15
Event

Atorvastatin 80mg
(22.4%)

10
16% RR
(P =
0.005)

5
0
0

12

15

18

21

Months of Follow-up

24

27

30

Summary of PROVE-IT Results

In patients recently hospitalized within 10 days for an

acute coronary syndrome:

Intensive high-dose LDL-C lowering (median LDL-C 62

mg/dL) compared to moderate standard-dose lipid-lowering
therapy (median LDL-C 95 mg/dL) reduced the risk of all cause
mortality or major cardiac events by 16% (p=0.005)

Benefits emerged within 30 days post ACS with continued benefit

observed throughout the 2.5 years of follow-up

Benefits were consistent across all cardiovascular endpoints,

except stroke, and most clinical subgroups

Invasive vs Conservative
Strategies

Invasive vs Conservative Strategy

Clinical Trials

VANQWISH (98)

ICTUS (05)

ISARCOOL
RITA-3 (02)

MATE

VINO

TIMI IIIB (94)

TRUCS
TACTICSTIMI 18 (01)

Weight of
the evidence

Conservative
Strategy Favored
N=920

No difference
N=2,874

FRISC II (99)
Invasive
Strategy Favored
N=7,018

How Early is Early?

Secondary Prevention
Class I Indications
Aspirin
Beta-blockers: (all pts, slow titration with moderate to
severe failure
ACE-Inhibitors: CHF, EF<40%, HTN, DM
(All pts-Class IIa) ARB when intolerant to ACE.
(Class IIa as alternative to ACEI)
Aldosterone blockade: An ACEI, CHF with either
EF<40% or DM and if CrCl>30 ml/min and K<5.0
mEq/L
Statins
Standard Risk Factor Management

Long-Term Antithrombotic Therapy at Hospital

Discharge after UA/NSTEMI
New

UA/NSTEMI
Patient
Groups at
Discharge
Medical
Therapy
without
Stent

ASA 75 to 162 mg/d

indefinitely (Class I,
LOE: A)

Bare Metal
Stent Group

Drug Eluting
Stent Group

ASA 162 to 325 mg/d for

at least 1 month, then 75
to 162 mg/d indefinitely
(Class I, LOE: A)

&

&
Clopidogrel 75 mg/d for at
least 1 month and up to 1
year
(Class I, LOE:B)

Clopidogrel 75 mg/d at
least 1 month (Class I,
LOE: A) and up to 1
year (Class I, LOE: B)

ASA 162 to 325 mg/d

for at least 3 to 6
months, then 75 to 162
mg/d indefinitely
(Class I, LOE: A)
&
Clopidogrel 75 mg/d
for at least 1 year
(Class I, LOE: B)

Indication for
Anticoagulation?
Ye
s

Add: Warfarin (INR 2.0 to

2.5) (Class IIb, LOE: B)

No

Continue with dual

antiplatelet therapy as
above

Anderson JL, et al. J Am Coll Cardiol 2007;50:e1e157, Figure 11. INR = international normalized ratio; LOE = level of evidence.

Secondary Prevention
Class III

Hormone Replacement Therapy

Antioxidants (Vit C, Vit E)
Folic Acid

New and Controversial

Drug Therapies

Early Treatment with Clopidogrel

Shortcomings of the CURE Trial

Conducted primarily at centers without routine

use of early invasive strategy
Only 462 (3.7%) patients enrolled from the U.S.
44% had catheterization during index
hospitalization
Adverse event reduced only in nonfatal MI set
Major Bleeding rate of 9.6% among patients
who were administered clopidogrel within 5
days of CABG

Clopidogrel
Bleeding Risk and CABG

In hospitals in which patients with

UA/NSTEMI undergo rapid diagnostic
catheterization within 24 hours of admission,
clopidogrel is not started until it is clear that
CABG will not be scheduled within the next
several days. However, unstable patients
should receive clopidogrel or be take for
immediate angiography.

Clopidogrel vs. Prasugrel

Prasugrel-Key Facts

Contraindicated in pts with prior TIA/Stroke

Not recommended for patients >75 years
5 mg maintenance dose suggested in patients
<60 Kg, though this dose has not been studied

Summary

ACS includes UA, NSTEMI, and STEMI

Management guideline focus

Immediate assessment/intervention (MONA+BAH)
Risk stratification (UA/NSTEMI vs. STEMI)
RAPID reperfusion for STEMI (PCI vs. Thrombolytics)
Conservative vs Invasive therapy for UA/NSTEMI

Aggressive attention to secondary prevention

initiatives for ACS patients

Beta blocker, ASA, ACE-I, Statin

Questions?