Acute Coronary

Syndromes

Definitions
Acute coronary syndrome is defined
as myocardial ischemia due to
myocardial infarction (NSTEMI or
STEMI) or unstable angina
Unstable angina is defined as
angina at rest, new onset
exertional angina (<2 months),
recent acceleration of angina (<2
months), or post revascularization
angina

Diagnosis
Dx of acute coronary syndrome is based on
history, physical exam, ECG, cardiac
enzymes
Patients can then be divided into several
groups
Non-cardiac chest pain (i.e.,
Gastrointestinal,
musculoskeletal,
pulmonary embolus)
Stable angina
Unstable angina
Myocardial infarction (STEMI or NSTEMI)
Other cardiac causes of chest pain (i.e.,
aortic dissection, pericarditis)

Pre-test Probability
In the absence of abnormal findings on
physical exam, ECG, or enzymes, the pretest probability of acute coronary
syndrome must be determined by the
clinician
A good history is crucial (is the
chest pain typical or atypical; what are
the associated symptoms)
Determination of risk factors is also
crucial (male, age >55, smoking, DM,
HTN, FamHx, hyperlipidemia, known CAD)

Pathophysiology of ACS
Plaque rupture and subsequent formation of
thrombus this can be either occlusive or
non-occlusive (STEMI, NSTEMI, USA)
Vasospasm such as that seen in
Prinzmetals angina, cocaine use (STEMI,
NSTEMI, USA)
Progression of obstructive coronary
atherosclerotic disease (USA)
In-stent thrombosis (early post PCI)
In-stent restenosis (late post PCI
Poor surgical technique (post CABG)

Pathophysiology of ACS
Acute coronary syndromes can
also be due to secondary causes
Thyrotoxicosis
Anemia
Tachycardia
Hypotension
Hypoxemia
Aterial inflammation (infection,
arteritis)

Treatment of ACS;
Aspirin
Aspirin is an antiplatelet agent
that initiates the irreversible
inhibition of cyclooxygenase,
thereby preventing platelet
production of thromboxane A2 and
decreasing platelet aggregation
Administration of ASA in ACS
reduces cardiac endpoints

Aspirin Trials

VA Cooperative Study
Canadian Multicenter Trial
RISC
Antithrombotic Trialists
Collaberation
PURSUIT

ACC/AHA Guidelines for

Aspirin Therapy
Aspirin should be given in a
dose of 75-325 mg/day to all
patients with ACS unless there
is a contraindication (in which
case, clopidogrel should be
given)

Treatment of ACS;
Nitrates
Nitroglycerin is considered a
cornerstone of anti-anginal therapy,
despite little objective evidence for
its benefit
Benefit is thought to occur via
reduction in myocardial O2 demand
secondary to venodilation induced
reduction in preload as well as coronary
vasodilation and afterload reduction
Titrate to relief of chest pain; chest
pain = death of myocardial cells
No documented mortality benefit

Treatment of ACS; Beta

Blockers
Beta Blockers reduce myocardial
oxygen demand by reducing heart
rate, contractility, and
ventricular wall tension
Administration of beta blockers
in ACS reduces cardiac
endpoints

Beta Blocker Trials

HINT (metoprolol)
Beta Blocker Heart Attack Trial
(propranolol)
Esmolol vs. placebo
Carvedilol vs. placebo
Propranolol vs. placebo
Overall, treatment with beta
blockers reduces primary endpoints
when compared to placebo

AHA/ACC Guidelines for

Beta Blocker Therapy
Intravenous beta blockers should be
used initially in all patients
(without contraindication) followed
by oral beta blockers with the goal
being decrease in heart rate to 60
beats per minute
A combination of beta blockers and
nitrates can be viewed as first
line therapy in all patients with
ACS

Treatment of ACS;
Heparin
Heparin (unfractionated heparin
or UFH) has traditionally been
the mainstay of therapy in
acute coronary syndromes as its
efficacy has been documented in
several large, randomized
trials

Heparin Trials

Heparin/Atenolol Trial
The Canadian Heparin/Aspirin Trial
The RISC Trial
Overall, UFH therapy generally
results in an important clinical
benefit when compared to placebo.
It is more effective when given in
continuous infusion rather than
intermittent boluses

Treatment of ACS; LMWH

More recent studies indicate
that low molecular weight
heparin is also effective in the
reduction of end points such as
myocardial infarction or death
Some studies report that LMWH,
when used in combination with
ASA, may be superior to
continuous infusion of Heparin

LMWH Trials

FRISC
TIMI IIB
ESSENCE
INTERACT
EVET

ACC/AHA Guidelines for

Heparin Therapy
All patients with acute coronary
syndromes should be treated with
a combination of ASA (325
mg/day) and heparin (bolus
followed by continuous infusion
with goal of PTT 1-2.5X control)
or ASA and low molecular weight
heparin unless one of the drugs
is contraindicated

Treatment of ACS; ACE-I

The best documented mechanism by
which these agents act is to reduce
ventricular remodeling over days to
weeks after myocardial damage.
However, there is data that a
mortality benefit exists when these
agents are used early in the course
of ACS
Administration of ACE-I in ACS
reduces cardiac endpoints

ACE-I Trials

GISSI-3 (Lisinopril)
ISIS-4 (Captopril)
SMILE (Zofenipril)
FAMIS (Fosinopril)
SAVE (Captopril)
TRACE (Trandolapril)
AIRE (Ramiripril)

AHA/ACC Guidelines for

ACE-I Therapy
ACE-I should be administered to
all patients in the first 24
hours of ACS provided
hypotension and other clear cut
contraindications are absent

Treatment of ACS;
Statins
Statins may be of benefit in
ACS
Possible mechanisms include
plaque stabilization, reversal
of endothelial dysfunction,
decreased thrombogenicity, and
reduction of inflammation

Statin Trials
MIRACL (modest benefit in
cardiac endpoints, no mortality
benefit)
SYMPHONY (no benefit)
There is no AHA/ACC class I
indication for use of statin
therapy in ACS

Treatment of ACS;
IIBIIIA Inhibitors
More potent inhibition of platelet
aggregation may be of importance in
patients with ACS that is
associated with unstable coronary
lesion and thrombus formation.
This can be achieved by the use of
GP IIBIIIA inhibitors
Administration of IIBIIIA
inhibitors reduces cardiac
endpoints

IIBIIIA Trials
PRISM-PLUS (Tirofiban prior to
PCI)
EPIC (Abciximab prior to PCI)
CAPTURE (Abciximab prior to PCI)
GUSTO IV-ACS (Abciximab no PCI)
PARAGON (Lamifiban no PCI)
PURSUIT (Eptifibatide -- no PCI)
RESTORE (Tirofiban no PCI)

AHA/ACC Guidelines for use

of IIBIIIA inhibitors
A IIBIIIA inhibitor should be
administered to all patients in
whom a percutaneous intervention is
planned (in addition to
heparin/ASA)
Eptifibatide or Tirofiban should be
administered to patients with ACS
in whom PCI is not planned if other
high risk features are present
(TIMI risk score >3)

TIMI Risk Score

Age >65 yrs
Daily ASA Therapy (>7 days prior to
event)
Symptoms of Unstable Angina
Documented CAD (stenosis > 50%)
3 or more traditional cardiac risk
factors
Elevated cardiac enzymes
ECG changes

TIMI Risk Score

Score of 3 or less = low risk
Score of 4-5 = intermediate
risk (use IIBIIIA)
Score of 6-7 = high risk (use
IIBIIIA)

Treatment of ACS;
Clopidogrel
Clopidogrel is a potent
antiplatelet agent
It should be administered to all
patients who cannot take ASA
The CURE trial suggests a benefit
to adding Clopidogrel to
ASA/Heparin in patients going for
PCI
Give 300 mg loading dose followed
by 75 mg/day

AHA/ACC Guidelines for

Clopidogrel
Clopidogrel should be administered to
patients who cannot take ASA because of
hypersensitivity or gastrointestinal
intolerance
In hospitalized patients in whom an
early, noninterventional approach is
planned, clopidogrel should be added to
ASA as soon as possible on admission
and administered for at least 1 month
and up to 9 months. Do not use
clopidogrel if there is any possibility
patient may be candidate for CABG

Treatment of ACS; Emergent

Revascularization
In the setting of STEMI primary
PCI is associated with better
outcomes than thrombolysis
Emergent PCI is also indicated
in the setting of a new LBBB

PCI Trials
PAMI (PTCA vs. thrombolysis)
Netherlands Trials (PTCA vs.
thrombolysis)
GUSTO IIB (PTCA vs.
thrombolysis)
DANAMI-2 (stenting vs.
thrombolysis)
STAT (stenting vs. thrombolysis)

AHA/ACC Guidelines for

Primary PCI
Primary PCI is indicated as an
alternative to thrombolysis when the
following criteria are met:
STEMI or new LBBB
Can undergo PCI within 12 hours of the
onset of symptoms
The MD doing the intervention does more
than 75 PCIs/yr
The procedure is done in a center that
does more than 200 PCIs/yr and has
surgical backup

Conclusions; Approach to
Chest Discomfort
Good History and Physical (note
time and duration of symptoms)
Careful evaluation of ECG
(compare to previous when
possible)
Check Cardiac Enzymes
Monitor on Telemetry
Oxygen

Conclusions; Treatment of
NSTEMI/USA

ASA
NTG (consider MSO4 if pain not relieved)
Beta Blocker
Heparin/LMWH
ACE-I
+/- Statin
+/- Clopidogrel (dont give if CABG is a
possibility)
+/- IIBIIIA inhibitors (based on TIMI
risk score)

Conclusions; Treatment
of STEMI

ASA
NTG (consider MSO4 if pain not relieved)
Beta Blocker
Heparin/LMWH
ACE-I
+/-Clopidogrel (based on possibility of
CABG)
IIBIIIA
+/- Statin
Activate the Cath Lab!!!