Unstable

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• Coronary artery disease (CAD) is the leading
  cause of death in the United States.
• Unstable angina (UA) and the closely related
  condition nonST-segment elevation myocardial
  infarction (NSTEMI) are very common
  manifestations of this disease and are
  responsible for approximately 1.5 million
  hospitalizations in the United States each year.
  UA and NSTEMI are examples of acute coronary
  syndrome (ACS)
• Only 500,000 admits are related to STE-myocardial
  infarction

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Recognition by patients medical staff
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Initial risk stratification

• Patient history, physical findings, ECG (goal
  within 10 minutes of arrival), biomarkers of
  injury
• Initial ECG not diagnostic but patient remains
  symptomatic and high suspicion for cardiac cause
  serial ECGs at 15-30 minute intervals
• Patients with negative biomarkers at 6hr beyond
  symptoms should have them repeated 8-12 hr after
  symptoms
• Traditional risk factors for CAD are less
  important than are symptoms, ECG findings, and
  cardiac biomarkers

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Pathophysiology
Imbalance between myocardial oxygen supply and
demand. The most common cause is the reduced
myocardial perfusion that results from coronary
artery narrowing caused by a nonocclusive thrombus
that has developed on a disrupted
atherosclerotic plaque.
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Definitions
UA and NSTEMI are considered to be closely
related conditions whose pathogenesis and
clinical presentations are similar but of
differing severity they differ primarily in
whether the ischemia is severe enough to cause
sufficient myocardial damage to release
detectable quantities of a marker of myocardial
injury such as troponin I levels
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Unstable angina is defined as angina pectoris
(or equivalent type of ischemic discomfort) with
at least one of three features (1) occurring at
rest (or with minimal exertion) and usually
lasting more than 20 minutes (if not interrupted
by nitroglycerin), (2) being severe and
described as frank pain and of new onset (i.e.,
within 1 month), and (3) occurring with a
crescendo pattern (i.e., more severe, prolonged,
or frequent than previously
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What classifies a NSTEMI?

• Troponin I/T- cardiac myocyte specific, can be as
  early as 2-4hr after the onset as long as
  8-12hrs
• Myocardial necrosis above the 99th percentile of
  normal Myocardial infarction
• Clinical scenario
• Does it make a difference?

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Estimation of level of risk

• Initial medical history, PE, ECG, renal function,
  and biomarker measurements
• 5 factors on the history
• Nature of anginal symptoms
• Prior history of CAD
• Sex (male)
• Older age
• Increasing number of traditional risk factors
• Likely, probable, or definite

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Tools to estimate risk

• TIMI risk score- predicts 30d and 1yr mortality
• PURSUIT
• GRACE
• Among patients with UA/NSTEMI, there is
  progressively greater benefit with increasing
  risk score from more aggressive therapies such as
  LMWH, GP IIbIIIa inhibition.

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TIMI risk score
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ECG Is the defining tool

• Transient ST segment changes (greater than or
  equal to 0.05mV) that develop during a
  symptomatic episode at rest strongly suggest
  acute ischemia due to severe CAD
• 4 of MI patients show ST elevation isolated to
  the posterior chest leads V7-V9
• Serial ECGs increase diagnostic sensitivity

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Chest pain units

• Prime focus is to reduce unnecessary hospital
  admissions
• Observation period with serial cardiac markers
  and ECGs and may then undergo functional cardiac
  testing or a noninvasive coronary imaging study,
  alternatively return within 72 hours for testing
• Initially set up for low risk patients
• Extension of this use into intermediate risk
  patients
• Modalities ETT, Nuclear, Echo, CTA, C-MR

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Early hospital care

• Definite or probable UA/NSTEMI pts who are
  hemodynamically stable and no recurrent symptoms-
  telemetry bed with frequent assessments
• Those high risk patients, hemodynamic
  instability, frequent symptoms- CCU
• Medical management
• Choice of invasive or an initially conservative
  strategy
• Assessment of LV function

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Early hospital care Anti-ischemic and analgesic
therapies

• Nitrates vasodilator with peripheral and
  coronary vascular effects resulting in reduction
  in myocardial oxygen demand and enhancement of
  myocardial oxygen delivery. Avoid if initial SBP
  less than 90mmHg
• Morphine sulfate Recent large observational
  study suggested a higher adjusted likelihood of
  death with morphine use therefore downgraded from
  class I to a IIa recommendation

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Early hospital care Anti-ischemic and analgesic
therapies

• Beta-adrenergic blockers block effects of
  catecholamines on cell membrane beta receptors.
• COMMIT study 45,000 patients with STEMI and
  NSTEMI, neither the composite of death,
  reinfarction, or cardiac arrest were reduced. A
  modest reduction in reinfarction/VF was
  counterbalanced by an increase in cardiogenic
  shock.
• Recommendations Initiate orally in the absence
  of HF, hypotension, AV block within the first 24
  hours. Strong recommendations for outpatient
  treatment

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Early hospital care Anti-ischemic and analgesic
therapies

• Calcium channel blockers Evidence based benefit
  for verapamil and diltiazem.
• Primarily in patients intolerant of BB or
  patients with variant angina.
• Obvious contraindications- pulm edema, LV
  dysfunction
• ACE-I reduce mortality rates in patients with AMI
  and LV dysfunction
• Aldosterone receptor blocker Eplerenone reduces
  mortality in patients with acute MI complicated
  by LV dysfunction

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Antiplatelet anticoagulant therapies

• Triple therapies in patients with continuing
  symptoms or other high risk features
• Platelets represent one of the principal
  participants in thrombus formation after plaque
  disruption
• Aspirin 162-325mg initially (non-EC) Inhibits
  COX-1
• Less bleeding risk with same therapeutic effect
  at lower dosages

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Antiplatelet anticoagulant therapiesAdenosine
diphosphate receptor antagonists (P2Y12)

• Thienopyridines ticlopidine clopidogrel
• Ticlopidine has data with MI/stroke but the
  adverse potentials of neutropenia and TTP has
  limited its use
• Clopidogrel has undergone extensive testing
• CAPRIE,CURE, PCI-CURE endpoints of CV death, MI,
  or stroke RR 0.8 30 reduction
• The optimal timing of administration (upstream vs
  in-lab) cannot be determined with certainty.
  Recommended if delay to angiography

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Antiplatelet anticoagulant therapies

• Clopidogrel has a role in both conservative and
  invasively managed patients
• Recommended treatment for 1 month and ideally 1
  year duration
• Drug eluting stents delay the neointimal coverage
  of stent struts and increase late thrombotic
  events thereby indefinite plavix use
• Major surgery that is unavoidable plavix should
  be withheld for 5 days
• Within the early stent implantation timing, high
  risk of peri-operative MI and death. Differs
  among the different stents

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Antiplatelet anticoagulant therapies

• Increasing number of anticoagulants
• UFH, enoxaparin, fondaparinux, and bivalirudin
  satisfies criteria for effectiveness, given the
  different study designs and patient populations
  it is difficult to conclude that one agent is
  more effective than another

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Antiplatelet anticoagulant therapies

• UFH- inactivates factor IIa(thrombin) and factor
  Xa difficult to dose and monitor but easy to
  stop and reverse
• LMWH- more potent than UFH in inhibiting factor
  Xa with a more predictable dosing and no lab
  monitoring, said to stimulate platelets less as
  well as less incidence of HIT
• Eight randomized trials have directly compared an
  LMWH with UFH the pooled OR was 0.91 with CI 0.83
  to 0.99 with it driven largely by a reduction in
  nonfatal MI although small inc bleeding with LMWH
• Maintain consistent anticoagulant therapy from
  the pre-PCI phase throughout hospitalization

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Antiplatelet anticoagulant therapies

• Bivalirudin- Direct thrombin inhibitor ACUITY
  trial 13,000 patients with multiple arms
  endpoint proved comparable to heparin and GP
  IIb/IIIa inhibition when combined with
  clopidogrel
• Fondaparinux- Factor Xa inhibitor
  OASIS-5 20,000 patients compared to LMWH
  satisfied non-inferiority with exception of PCI
  arm (now only medical conservative treatment)

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Antiplatelet anticoagulant therapies

• Platelet glycoprotein IIb/IIIa antagonists
• Abciximab- indicated for immediate PCI only,
  longer acting (24-48hr)
• Eptifibatide- classic one for medical treatment
  shorter acting, renal dosing
• Tirofiban- not used much
• The efficacy of IIb/IIIa antagonists for
  prevention of PCI related complications has been
  documented in several trials. Treatment effect
  is greatest in troponin positive patients.
• Lower heparin doses decrease the rate of bleeding

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• Statins Armyda-ACS trial- only 160 patients but
  benefit strong in patients treated early with
  Lipitor
• Guidelines do not mention statins acutely
• Female population- Less likely to have positive
  troponins question of whether low risk patients
  should be managed invasively
• Significant risk assoc with renal failure patients