Acute Coronary Syndrome

Acute Coronary Syndrome
The Essentials
Percy Pentecost, MD
University of New Mexico
School of Medicine

Impact
Incidence:
3 million people
estimated to have
acute ST-elevation MI
each year
4 million people
estimated to have nonST-elevation MI
A Shift in
Populations
Myocardial Infarction
used to be seen
predominantly in
developed countries,
but
it is now becoming
increasingly more
common in developing
countries..

Impact
Progressive
Why a shift
urbanization.
towards developing
countries as well?
Increasing rates of
obesity
Increasing rates of
diabetes
Increasing rates of
coronary heart disease

Impact
Why is this
epidemiology stuff
important anyway?
According to the
INTERHEART study
of over 15,000
patients, 90% of
myocardial
infarctions were
attributable to
modifiable risk
factors in men, and
94% in women!!!

Risk Factors
..modifiable risk
factorssuch as
Smoking
Dyslipidemia
Hypertension
Abdominal Obesity
Diabetes

Definitions
Acute Coronary
Syndrome
describes a
spectrum of
conditions
Unstable Angina
Non-ST-elevation
ST-elevation

Definitions
Acute Coronary
Syndrome
describes a
spectrum of
conditions
Unstable Angina
Non-ST-elevation
Myocardial
Infarction
ST-elevation

Definitions
Unstable Angina
vs. Non-STelevation
Myocardial
Infarction..is there
a difference?
Patients with these

two entities often
present similarly
Distinction between
the two can be made
only many hours to
days later when the
results of the cardiac
enzymes are
available

Definitions
Even though, STelevation MIs
sound more
exciting..theyre
not
Acute Coronary
Syndromes
account for 1.57
million
hospitalizations
each year
1.24 million of
those are for
Unstable Angina
and NSTEMI
Only .33 million are
for STEMI

Definitions
Quick QuizA 75
y/o man presents
to you with new
onset exertional
chest pain x 1
dayIs this stable
or unstable
angina?

Definitions
So what?
unstable angina
implies that there
is an unstable or
ruptured plaque
which is bad news..

Pathogenesis
Disruption of a
formed
atherosclerotic
plaque is central
to the initiation of
acute coronary
syndromes

Pathogenesis
Quick Quiz
Which type of
plaques are the
most vulnerable to
rupture big
plaques or small
plaques???

Pathogenesis
The arterial lesions
of patients with
unstable angina
frequently have
complex, eccentric
morphologic features
on angiography that
have been found to
represent ruptured
plaque with
superimposed
thrombus

Pathogenesis
Mature plaques are
made up of (1) a
lipid-rich core and (2)
a fibrous cap
The presence of
large, eccentric lipid
pools and infiltration
of foam cells are
most frequently
associated with
fissured or ruptured
plaques

Pathogenesis
The majority of
these plaques
rupture at sites of
greatest
mechanical
stress, notably at
the junction of the
plaque cap and
the adjacent
normal intimaor
the shoulder

Pathogenesis
Local thrombosis
occurring after plaque
disruption results from
complex interactions
among lipid core,
smooth-muscle cells,
macrophages, and
collagen..
The lipid core is the most
potent substrate for
platelet-rich thrombus
formation, and both
smooth-muscle and foam
cells within the core
increase expression of

Pathogenesis
So, why is this
important??
Unstable angina is the

part of a spectrum of
conditions that can
lead to complete
thrombosis and
infarction
It is paramount to
identify patients at
high risk early in order
to prevent progression
of this condition

Pathogenesis
Andknowing the
Anti-platelet
pathogenesis will
therapy
also help you
Anti-thrombin
understand the
medical therapy for
therapy
acute coronary
Anti-ischemic
syndromes
therapy

Risk Stratification and
Management
What do we mean
by risk
stratification?
The relative instability

of a plaque is a huge
unknown
so risk stratification
helps us delineate
how likely it is for a
given patient to
progress to full
infarction, or death

The TIMI
(Thrombosis in
Myocardial
Infarction) Trials
The TIMI Risk score

accurately predicts
the risk of an
adverse cardiac
event in the setting
of a suspected
Acute Coronary
Syndrome
The TIMI Risk

Factors
one point for
each
Age 65 years
At least 3 risk factors for
CAD
Prior coronary stenosis of
50%
ST-segment deviation on
ECG presentation
At least 2 anginal events in
prior 24 hours
Use of aspirin in prior 7
days
Elevated serum cardiac
biomarkers
The TIMI Risk

Score
Composite
primary outcome
measure = Allcause mortality,
recurrent MI,
urgent coronary
revascularization
The TIMI Risk Factors

Score Component
P Value
Odds Ratio (95% CI)
Age 65
<0.001
1.75[1.35-2.25]
3 CAD risk factors
0.003
1.54[1.16-2.06]
Significant Coronary
stenosis
<0.001
1.70[1.30-2.21]
ST deviation
0.005
1.51[1.13-2.02]
Severe angina
0.001
1.53[1.20-1.96]
Aspirin in last 7 days
0.006
1.74[1.17-2.59]
Elevated biomarkers
0.001
1.56[1.21-1.99]
Case 1A 75 y/o man

with a h/o HTN, DM, and
smoking presents with a
2 day history of
progressively worsening
angina. He has had
multiple episodes in the
past 24 hours. He takes
HCTZ, glyburide, and a
baby aspirin daily. On
exam, vitals stable, ECG
normal. Initial troponin
elevated at 1.52.
What is his TIMI risk

score? And what does this
mean?
TIMI Risk Factors(5)
3 CAD risk factors

Age 65
2 anginal events in 24
Aspirin in past 7 days
Elevated biomarkers
Composite Primary
Outcome ~ 26.2%
chance of death, MI, or
need for urgent
revascularization
Case 2A 50 y/o woman

with a history of DM, HTN,
and Smoking presents
after an episode of angina
while walking up a flight of
stairs this morning. She
has had no further
episodes. She takes
glyburide. On exam, vitals
stable. ECG normal, and
cardiac enzymes negative.
What is her TIMI

risk score?
TIMI Risk Factors
(1)
Risk ~ 4.7%
So, the TIMI risk

assessment tool
helps a clinician
estimate the risk
involved in an ACS
presentation
it also helps
guide the initial
evaluation and
management of
ACS

Initial Therapies and
Management
Classification of
Recommendation and
Level of Evidence
Classification of
Recommendation and Level
of Evidence
To summarize,
Recommendations
Class I if you dont do
this, youre an idiot..
Class II you should
probably do this too..
Class III you may find
a reason not to do
this
Class IV if you do this
youre an idiot
And Evidence
Class A lots of
great evidence
Class B a little bit
of good evidence
Class C my
grandfather taught
me this

Therapies and Management
Remember the
problem
plaque rupture,
platelet
aggregation
Thrombosis
Occlusion of
vessel..decreased
oxygen supply to
myocardium
Helps with the

solution
Anti-ischemic
therapy (reduce
demand/ increase
supply)
Anti-platelet
therapy
Anti-thrombin
therapy

Anti-Ischemic
therapy..
Bed Rest
Continuous ECG
monitoring
Supplemental oxygen
Nitroglycerin
Beta-blockers
IV morphine
IABP for hemodynamic
instability
ACE inhibitor for persistent
HTN in patients with
persistent systolic
dysfunction or CHF

Anti-Ischemic
therapy..
Bed Rest Class IC

recommended for all
ACS patients on
presentation
Supplemental O2
Class IB should be
given in ACS patients
with O2 sat <90%,
respiratory distress, or
other high risk
features of hypoxemia

Anti-Ischemic
therapy..
Sublingual Nitroglycerin
class IC Patients with
ACS should receive
sublingual NTG (0.4 mg)
every 5 for a total of 3
doses after which
assessment should be
made about the need for
IV NTG
Intravenous
Nitroglycerin class IB
is indicated in the first 48
hours after ACS for
treatment of persistent
ischemia, CHF, or HTN

Anti-Ischemic
therapy..
Oral beta blocker

therapy Class IB
should be initiated within
the first 24 hours for
patients who do not have
(1) CHF, (2) low CO, (3)
increased risk for
cardiogenic shock, (4)
evidence of AVB, or (5)
reactive airway disease

Quick Quiz
What is the
estimated mortality
benefit of beta
blockers in the
setting of acute
coronary
syndrome?
Yusof et al. JAMA 1988;260:2259-63

Quick QuizDo
nitrates improve
mortality?

More questions
what adaptive
response occurs
within 24 hours
of nitrate
therapy?

Anti-Ischemic
therapy..
ACE Inhibitor class IA

Should be given orally
within first 24 hours to ACS
patients with pulmonary
congestion, or LV EF <40%
in the absence of
hypotension or other
contraindications.
ARB Can be
administered to ACS
patients intolerant to ACE
inhibitors.

Anti-Ischemic
therapy..
Calcium Channel
Blockers class IB In
ACS patients with
continuing or recurrent
ischemia, and in whom
beta blockers are
contraindicated, nondihydropyridine CCB
(diltiazem, or verapamil)
should be given as initial
therapy in the absence of
clinically significant LV
dysfunction.

Anti-Ischemic
therapy..
NSAIDS class IC
because of increased risks
of mortality, reinfarction,
hypertension, CHF, and
myocardial rupture
associated with their use,
NSAIDs (except ASA)
whether selective or nonselective COX inhibitors
should be discontinued
at the time a patient
presents with an ACS.

Just one example
What is the
issue?
COX 1 mediates
platelet production of
thromboxane A2
(prothrombotic)
COX 2 mediates
endothelial cell
synthesis of
prostacyclin
(antithrombotic)
So selective COX 2
inhibition will result in
unopposed
thromboxane
production by
platelets

Anti-Ischemic
therapy..
Oxygen class IIC it is

reasonable to give
supplemental oxygen
during the first 6 hours
after presentation in ACS
Morphine class IIB in
the absence of
contraindications to its
use, it is reasonable to
administer morphine
sulfate intravenously to
ACS patients if there is
uncontrolled ischemic
chest discomfort despite
nitrogylcerin

Anti-Ischemic
therapy..
Intra-aortic balloon
pump (IABP) class IIC
--counter pulsation is
reasonable in ACS patients
for severe ischemia that
recurs frequently despite
intensive medical therapy,
for hemodynamic
instability in patients
before or after
angiography, and for
mechanical complications
of MI.

Anti-Ischemic
therapy..
Nitrates should NOT be

given in ACS patients
with SBP <90, severe
bradycardia,
tachycardia in the
absence of CHF, or RV
infarction (class IIIC)
Nitrates should not be
given to ACS patients
who have received a
phosphodiesterase
inhibitor for erectile
dysfunction within 24
hours of sildenafil and
48 hours of tadalafil use
(class IIIC)

Anti- Platelet
Therapies
Aspirin
Clopidogrel
GP IIBIIIA Inhibitors
Heparin

Therapies and
Management
Antiplatelet
therapies

Antiplatelet
therapies
Aspirin class IA
should be given ASAP
unless there is known
intolerance
Clopidogrel class IA
should be given to
ACS patients who are
unable to take ASA

Antiplatelet
therapies
Glycoprotein IIB/IIIA
inhibitors
consistently reduce
30-day relative risk of
composite endpoint of
death, MI, or need for
repeat
revascularization (22
to 56%) when given
with heparin and
aspirin, but not when
given alone

Antithrombin
therapy..
What about
heparins?
Unfractionated heparin
evidence shows a 33%
lower incidence of MI or
death when given in
combination with aspirin
LMWH TIMI IIB study
showed that enoxaparin is
superior to UFH in reducing
MI and emergent
revascularization, but no
mortality difference.
ESSENCE trial showed that
LMWH was superior in all
endpoints.

And finallySelect
Management
Strategy
Initial Invasive
versus Initial
Conservative
Strategywho will
benefit from early
catheterization and
intervention?

Back to the TIMI

risk score
Age 65 years
At least 3 risk factors for
CAD
Prior coronary stenosis of
50%
ST-segment deviation on
ECG presentation
At least 2 anginal events in
prior 24 hours
Use of aspirin in prior 7
days
Elevated serum cardiac
biomarkers

It turns out that the
TIMI risk score is
useful in predicted
who will benefit
from early invasive
therapy
Low risk Score

Treat
conservatively with
medical
management
High risk Score
Treat with early
invasive therapy

The
Recommendations
Class IB - An early invasive

strategy is indicated in ACS
patients who have
refractory angina,
hemodynamic or electrical
instability
Class IA An early invasive
strategy is indicated in
initially stabilized ACS
patients who have an
elevated risk for clinical
events per the TIMI risk
score

TACTICS-TIMI-18
Trial
2,220 patients
within 24 hours of
ACS
Meds: ASA, heparin,
tirofiban
Cannon CP, et al. NEJM 2001;344:1879-87
Showed decreased death,

MI, and rehospitalization
for ACS at 6 months for
invasive strategy
Benefit in medium and
high risk patients (TIMI risk
>3, ST segment deviation,
elevated troponin)
For patients with no high
risk features there was
equivocal benefit
Decreased death and MI at
6 months for older
patients
Benefit in high risk women
Low risk women tended to
have worse outcomes

In an early invasive
strategy, the
therapy is a little
more aggressive
Yusuf et al, NEJM 2001:345:494-502
Class IA antiplatelet
therapy in addition to
ASA should be
initiated before
angiography with
either clopidogrel or a
GP IIB/IIIA inhibitor
CURE trial showed a
decrease in all
composite endpoints
with clopidogrel but an
increased risk of major
bleeding as well.

strategy, the
therapy is a little
more aggressive
NEJM 1998;339:436-43
PURSUIT trial showed

that the IIB/IIIA
inhibitor eptifibatide
decreased deaths and
MI at 96 hours, 7d,
and 30 d compared to
placebo
An additional 11%
decrease in events
with concomitant
heparin

Contraindications
to gpIIB/IIIA
therapy
Active or recent bleeding

(4-6 weeks)
Severe hypertension
Any hemorrhagic CVA
Any CVA within 30 days to
2 years
Major surgery or trauma
within 4-6 weeks
Thrombocytopenia
(<100,000)
Bleeding diathesis/
warfarin with elevated INR

strategy, the
therapy is a little
more aggressive
Class IA/IB
anticoagulant
therapy should be
added to
antiplatelet
therapy in ACS
patients ASAP.

strategy, the
therapy is a little
more aggressive
ESSENCE trial
showed that
enoxaparin was
superior to UFH in
reducing death, MI,
or recurrent angina
at 14d, 30d and 1
year in ACS
patients.

Class 1
Long term medical

therapy
Aspirin
Clopidogrel
Combined ASA +
Clopidogrel for 9
months for NSTEMI
Beta blockers
Lipid lowering agents
Ace inhibitor if LV
dysfunction, HTN, or
diabetes
Smoking cessation
Diet/ Lifestyle
modification

Heart Protection
Study (20,536
patients with CHD)
One special note
about lipid control,
and statins
Lancet 2002;360:7-22
Simvastatin vs.
placebo
Decreased total
rates of CHD, total
stroke,
revascularization
Statins
recommended in
all patients at
discharge
regardless of
baseline LDL-C

Clinical Question:
What are the blood
pressure, LDL, and
Hgb A1C goals in
CAD patients?
LDL goal <100

class IA, and <70
class IIA
BP goal is <140/90
in CAD patients,
and <130/80 in
CAD patients with
DM, or CKD
A1C goal is < 7%
The End
References
The TIMI Risk Score for Unstable Angina/Non-ST Elevation MI, JAMA 200; 284:835-842
Chew DP and White HD. Acute Myocardial Infarction. Lancet 2008; 372:570-84
Yeghiazarians Y, Braunstein JB, Askari A, Stone PH. Unstable Angina Pectoris. New
England Journal of Medicine. 342(2): 101-114
http://static.flickr.com/56/151606719_95d2a462ed.jpg
http://www.medscape.com/content/2002/00/43/64/436408/art-jic436408.fig1.gif
http://www.panaceia-or-hygeia.com/Images/PlaqueRupture-Thrombus.jpg
http://www.kup.at/kup/images/thumbs/750.jpg
http://jnm.snmjournals.org/cgi/content-nw/full/45/11/1898/F3
http://www.acc.org/qualityandscience/clinical/guidelines/STEMI/Guideline1/Images/tab
le1.jpg
http://www.australianprescriber.com/upload/issue_files/3004_f1_antiplatelet.gif
http://www.fiery-foods.com/ffshow/images/sandia_mountains.jpg

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