Transcript Acute Coronary Syndromes

Acute Coronary Syndromes
Robert Smith
August 4, 2003
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 pre-test 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 nonocclusive (STEMI, NSTEMI, USA)
• Vasospasm such as that seen in Prinzmetal’s
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
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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
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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 antianginal 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
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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
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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
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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
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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
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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
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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
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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
PCI’s/yr
– The procedure is done in a center that does more than
200 PCI’s/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
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ASA
NTG (consider MSO4 if pain not relieved)
Beta Blocker
Heparin/LMWH
ACE-I
+/- Statin
+/- Clopidogrel (don’t give if CABG is a
possibility)
• +/- IIBIIIA inhibitors (based on TIMI risk score)
Conclusions; Treatment of
STEMI
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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!!!