Transcript Unstable - Tripod.com

Coronary artery disease (CAD) is the leading cause of death
in the United States.
Unstable angina (UA) and the closely related condition non–
ST-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
Recognition by patients & medical staff
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 ECG’s 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
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.
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
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
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?
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
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.
TIMI risk score
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 ECG’s increase diagnostic sensitivity
Chest pain units
• Prime focus is to reduce unnecessary hospital
admissions
• Observation period with serial cardiac markers and
ECG’s 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
Early hospital care
• Definite or probable UA/NSTEMI pts who are
hemodynamically stable and no recurrent symptomstelemetry 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
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
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
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
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
Antiplatelet & anticoagulant therapies
Adenosine 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 inlab) cannot be determined with certainty.
Recommended if delay to angiography
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
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
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
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)
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
• 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