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Management of
Unstable Angina / Non
ST Elevation Myocardial
Infarction
Treatment Goals for UA / NSTEMI
Treatment Goals for UA / NSTEMI are:
1. Stabilize & Passivate the acute coronary lesion
2. To treat residual ischemia
3. To employ long term secondary prevention
Therapy Options
Antithrombotic Therapy:
1. Used to Prevent further thrombosis
2. To allow endogenous fibrinolyses to
dissolve the thrombus
3. To reduce the degree of coronary
stenosis
4. Therapy Continued for long term to
reduce the risk of developing future
evnts or to reduce the risk of complete
occlusion of coronary artery.
Therapy Options
Antiischemic Therapy:
1. Are used primarily to reduce
myocardial oxygen demand
2. They have also shown to
have an effect in preventing
plaque rapture.
Therapy Options
Coronary Revascularization
1. Frequently used used to
treat severe stenosis of
culprit lesion
2. Thereby preventing the
thrombus from
progressing & causing
recurrent ischemia.
Therapy Options
After the acute event is stabilized, the many factors that
have led to the event need to be reversed, that is
treatment of atherosclerotic risk factors such as:
1. Hypercholesterolemia
2. Hypertension
3. Cessation of Smoking
General Measures
• Patients with UA/NSTEMI should be admitted to a
monitored bed.
• Continuous ECG monitoring (telemetry) is used to
detect cardiac arrhythmias
• High fidelity ECG tracings can be obtained with a Holter
monitor and can assess asymptomatic ST deviations as
markers for ischemia
• Bed rest is usually prescribed.
• Ambulation as tolerated is permitted if patient has been
without recurrent chest discomfort for atleast 12 to 24
hours.
• It is advisable to provide supplemental oxygen only to
patients with cyanosis, extensive rales or documented
hypoxemia.
• In patients with persistent pain despite nitrate & betablockers, morphine sulfate 1 to 5mg intravenously is
recommended
Nitrates
• Nitrates should be given sublingually or by buccal
spray if the patient is experiencing ischemic pain.
• If pain persists intravenous nitroglycerin is
recommended.
• Oral nitrates may replace the intravenous nitroglycerin
if the patient has been pain free for 12 to 24 hours.
• Attempt should be made to have an 8-10 hour nitratefree interval.
• Consequently the goal of nitrate therapy is relief of pain.
• Chronic nitrate therapy can be tapered off in the long
term management of patients, with sublingual or buccal
nitrates given as needed for new episodes of pain.
Beta-Blockers
• Studies have shown that Beta Blockers are beneficial in
reducing subsequent MI or recurrent Ischemia or both.
• If ischemia & chest pain are ongoing early IV beta
blockade can be used.
• The choice of beta blocker can be made individually on
the basis of the drug’s pharmacokinetics, cost &
familiarity.
• However, those with intrinsic sympathomimetic activity
should not be selected.
• Examples of doses tested in large trials include –
Atenolol and Metoprolol.
Calcium Channel Blockers
• They have vasodilatory effects and lower blood
pressure and some also slow heart rate.
• They are currently recommended in patients who have
persistent ischemia after treatment with full dose
nitrates & betablockers.
• Dilitiazem should be avoided in patients with left
ventricular dysfunction, congestive heart failure or both.
• No harm has been observed with amlodipine and
felodipine in patients with documented LV dysfunction
and CAD, indicating that vasoselective calcium agonists
may be safely used in patients with UA/NSTEMI with LV
dysfunction.
Angiotensin-Converting Enzyme Inhibitors
• Three large trials showed a 0.5% absolute mortality
benefit (initiated within 24hours) of early ACE inhibition
• However, in ISIS-4 study no benefit was observed in
patients without ST elevation.
• Thus short term ACE inhibition does not appear to
confer any benefit for patients with UA/STEMI
• On the other hand long term use of ACE inhibition is
beneficial in preventing recurrent ischemic events &
mortality.
• Studies like SAVE, SOLVD, HOPE & EUROPA have
established the long term antiischemic effect of ACE
inhibitors in a broad population of patients.
Lipid Lowering Therapy
• 4S study has shown not only a reduction of mortality by
30% in patients with hypercholesterolemia & MI or
Unstable angina by also showed that MI is reduced by
37%, coronary revascularization by 37% and
hospitalization for acute CV disease by 26%.
• MIRACL trial found that short term (4 mnths) treatment
with high dose atorvastatin reduced cardiac death, non
fatal MI, resuscitate SCD, or urgent rehospitalization for
recurrent ischemia by 16%. Even PROVEIT-TIMI 22 has
similar findings with intensive statin therapy.
• Thus studies have demonstrated the early use of highdose statins following ACS is beneficial in reducing
recurrent cardiac events or death
Antithrombotic Therapy - Aspirin
• Several Trials have demonstrated clear beneficial
effects of aspirin, with a more than 50% reduction in the
risk of MI or death in patients presenting US/NSTEMI.
• The benefit emerges within the first day of the
treatment.
• Thus aspirin has a dramatic effect in reducing adverse
clinical events early in the course of treatment of
UA/NSTEMI and thus is primary therapy in these
patients.
Antithrombotic Therapy –
Clopidogrel & Ticlopidine
• Clopidogrel & Ticlopidine are thienopyridine derivatives
that inhibit plateley aggregation, increase bleeding time
and reduce blood viscosity by inhibiting ADP action on
platelet receptors
• Studies have shown that achievement of effective levels
of platelet inhibition with clopidogrel in PCI is effective
in reducing events.
Antithrombotic Therapy – Direct
Thrombin Inhibitors
• Direct thrombin inhibitors (factor IIa) have undergone
extensive evaluation. The prototypic agent is hirudin, a
natutrally occuring anticoagulant from medicinal leech.
• Hirudin which is manufactured with recombinant DNA
technique binds directly to thrombin, independent of
antithrombin.
• A meta analysis of all Hirudin trials have shown a
modest 10% benefit favoring hirudin which is not
statistically significant for patients with UA/NSTEMI
• Bivalirudin has been tested durin PCI and found to have
a trend toward superior outcomes compared to UFH.
• However the efficacy of bivalirudin has not been fully
studied.
Antithrombotic Therapy –
Glycoprotein IIb/IIIa Inhibitors
• GP IIb/IIIa inhibitors are potent inhibitors of platelet
aggregation.
• Several studies have shown benefit of IIa/IIIb inhibition
in UA/NSTEMI in patients receiving predominantly
medical management, early internetional management
or both.
• In PRISM-PLUS study tirofiban+heparin+aspirin
significantly reduced the rate of death, MI or refractory
ischemia at 7 days compared with heparin+aspirin.
Revascularization – Percutaneous
Coronary Intervention
• PCI is an effective means of reducing coronary
obstruction, improving acute ischemia and improving
regional and global ventricular function in patients with
UA/NSTEMI
• Current angiographic success rates are high, generally
greater than 95%, although the presence of UA/STEMI
or visualized thrombus is associated with an increased
risk of acute complications such as abrupt closure or
MI.
• Thus the use of antithrombotic agents are
recommended to improve acute & long term outcome
following PCI.
• Use of drug eluting stents have shown to reduce the
risk of restenosis.
Revascularization – PCI Vs CABG
• More than 8 trials have compared PCI & CABG. On the
basis of the results CABG is recommended for patients
with disease of the left main artery, multi-vessel
disease, and impaired LV-function.
• For other patients either PCI or CABG may be suitable.
• PCI is associated with slightly lower initial morbidity &
mortality than CABG but a higher rate of repeated
procedures.
• CABG is associated with more effective relief from
angina.
Revascularization – Intraaortic
Balloon Counterpulsation
• IABP is an effective means of increasing diastolic
coronary blood flow and reducing left ventricular
afterload, which act in concert to reduce ischemia.
• IABP is usually reserved for patients with UA/NSTEMI
who are refractory to maximal medical therapy, those
with hemodynamic compromise who are awaiting
cardiac catheterization, or those with very high risk
coronary anatomy.
• Although no randomized trials have documented the
benfeit of IABP, this method is effective in stabilizing
patients with refractory ischemia.
Management Algorithm for lower
risk patients with UA/NSTEMI
Lower Risk
Stress Test
+ High Risk
+ Not High Risk
Negative
Coronary
Angiography
Statin, ACEI,
outpatient Rx
Consider
Alternative
Diagnosis
High-risk
pathway
Management Algorithm for High or
Medium risk patients with UA/NSTEMI
High Intermediate Risk
Coronary Arteriography
Left Main Coronary
Disease+LV
dysfunction or
Diabetes Mellitus
1 0r 2 Vessel Disease,
Suitable for PCI
IIb/IIIa inhibitors
CABG
PCI
Discharge on ASA, Clopidogrel, Statin, ACE-I
Normal
Consider
Alternative
Diagnosis