Treatment of Non-ST elevation myocardial Infarction

3 basics
1) Anti-ischemic agents

2) Antithrombotic agents

3) Coronary revascularization

Anti-ischemic agents

Decrease myocardial oxygen demand

Increase myocardial oxygen supply/ availability

• Nitrates
IV nitrates more e cacious than sublingual nitrates in symptoms relief , and regression of ST
depression

Titrate the dose upwards until symptoms are relieved.

After symptom control is achieved stop nitrates

Do not administer nitrates if patient has phosphodiesterase type 5 inhibitor due to risk of severe
hypotension

• Beta blockers

Competitively inhibit the myocardial e ect of circulating catecholamines

Reduce myocardial oxygen consumption by lowering heart rate, blood pressure, myocardial
contractility

8% relative risk reduction for in hospital mortality associated with beta blockers, with no increase
in cariogenic shock

DO NOT administer beta blockers

If the ventricular function is unknown

In patients with symptoms possibly related to coronary vasospasm

In patients with cocaine use

Anticoagulants

To inhibit thrombin generation and/or activity, thereby reducing thrombus-related events

Anticoagulation is e ective in addition to platelet inhibition

Combination of anticoagulation and platelet inhibition is more e ective than either treatment alone

Low molecular weight heparin

Heparin derived anti-X1 and anti-IIa compounds with molecular weight ranging from 2000 to
10,000 Da

LMWH Unfractionated Heparin

Complete absorption after subcutaneous

administration

Less protein binding

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 Treatment of Non-ST elevation myocardial Infarction

LMWH Unfractionated Heparin

Less platelet activation

More predictable dose-e ect relationship

Lower risk of heparin induced thrombocytopenia

Same e cacy

Same safety end-points

Same risk of major bleeding

LMWH eliminated at least partially by kidneys

If renal function deteriorates, LMWH accumulates in blood increasing the bleeding risk

Most LMWHs are contraindicated in the case of renal failure with creatinine clearance less than 30
mL/min

For enoxaparin if creatinine clearance is less than 30 mL/min —-> 1mg/kg once daily

Limit duration of anticoagulation only to the acute phase

6-8% of patients presenting with NSTE-ACS have an indication for long term oral anticoagulation

1) moderate to high embolic risk atrial brillation

2) mechanical heart valves

3) venous thromboembolism

If a NSTE-ACS occurs in a patient who is already taking oral vitamin K antagonists, do not stop
oral anticoagulation because stopping the vitamin K antagonist and bridging with parenteral
anticoagulants may lead to increased rate of both thromboembolic episodes and bleeds

Duration of triple therapy ( aspirin, clopidogrel and oral anticoagulant )

1 month to maximum 6 months after PCI

Dual Antiplatelet therapy for at least for 12 months with or without PCI and stent implantation
unless the bleeding risk is very high

Dual therapy (with oral anticoagulant + clopidogrel , omit aspirin) may be considered for patients
at very high bleeding risk

Antiplatelet agents

Start early as possible when the diagnosis of NSTE-ACS is made

Reduce the risk of acute ischemic complications

Reduce the risk of recurrent atherothrombotic events

• Aspirin
Irreversibly inhibits platelet derived cyclooxygenase-1

Reduce the formation of thromboxane A2

Inhibits platelet activation

Aspirin reduces the incidence of recurrent MI or death ion patients with Unstable Angina

Loading dose of chewed, plain aspirin between 150 mg and 300 mg

No statistical di erence between higher dose ( 300-325 mg/day) and lower dose (75mg-100 mg/
day) as demonstrated by Clopidogrel Optimal Loading dose Usage to Reduce recurrent Events/
Optimal Antiplatelet strategy for Interventions (CURRENT-OASIS) trial

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 Treatment of Non-ST elevation myocardial Infarction

Aspirin for lifetime for secondary prevention

If intolerant to aspirin, can use clopidogrel monotherapy

P2Y12 receptor inhibitors (Adenosine diphosphate receptor antagonists)

• Clopidogrel
Inactive prodrug

Two step liver metabolism activates it: dependent on cytochrome P450 isoenzymes CYP3A4
and CYP2C19

85% of the prodrug is hydrolysed by esterase into an inactive form

15% of the prodrug available for transformation into active metabolite

Active metabolite selectively and irreversibly inactivates platelet P2Y12 receptors

DAPT with aspirin and clopidogrel

Reduce recurrent ischaemic event in NSTE-ACS setting compared with aspirin alone

CURE trial ( Clopidogrel in Unstable angina to Prevent Recurrent Events trial )

Loading dose of 300 mg

75 mg maintenance dose for 9 months

In addition to aspirin

20% risk reduction at 12 months of cardiovascular death and non-fatal MI or stroke compared
with aspirin alone in patients with NSTE-ACS

38% increase in the rate of major bleeding events, but with a non-signi cant increase in life-
threatening and fatal bleeds

600 mg loading dose has more rapid onset of action and more potent inhibitory e ect than the
300 mg dose

Clopidogrel should be withdrawn for 5 days before major surgery

Coronary revascularisation

Do a risk strati cation

The subgroups of patients at high-risk that bene t from an early invasive management are

Diabetes mellitus

Elderly

Patients with renal insu ciency

Apply a prede ned risk-score such as the GRACE risk score (Global Registry of Acute Coronary
events)

GRACE risk score predict the in-hospital mortality risk of patients with NSTEMI and STEMI

Revascularization modalities

Percutaneous coronary intervention - Stenting ( Drug eluting stent >>> Bare metal stent )

Coronary Artery Bypass Graft

Revascularization for NSTE-ACS

Releives symptoms

Shortens hospital stay

Improves prognosis

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 Treatment of Non-ST elevation myocardial Infarction

Very high risk patients ——> immediate invasive strategy ( < 2 h )

High risk patients (GRACE score 141- 372 ) ——> early invasive strategy ( < 24 h )

Intermediate risk patients (GRACE score 109- 140 ) ——> Delayed invasive strategy, but the
maximum delay should be less than 72 hours

Low risk patients (GRACE score 1- 108) ——> A non-invasive assessment of inducible ischemia
(stress test) before discharge from the hospital to deciding on an invasive strategy

If the non-invasive stress test is positive for reversible schema ——> coronary angiography

Patients at very high risk who need immediate invasive strategy ( < 2 h ) are patients with

Refractory angina

Severe heart failure

Life threatening ventricular arrhythmias

Haemodynamic instability

Mechanical complications of MI

Recurrent ST-T wave changes, particularly with intermittent ST elevation

These patients should receive immediate Coronary angiography

If a patient had an out-of hospital cardiac arrest + no ST elevation on ECG

If the survivor is conscious ——> need immediate coronary angiography

If the survivor is comatose ——> investigate for non-coronary conditions, if appropriate and
coronary angiography should be performed directly after in the absence of an obvious non-
coronary cause of the cardiac arrest

Early invasive strategy ( < 24 h )

Early invasive strategy is coronary angiography performed within 24 h of hospital admission

Early invasive strategy brings bene t in patients at high risk

So if a patient has at least one high-risk criterion need to undergo early invasive strategy

Conservative treatment in patients with coronary artery disease

Non-obstructive Coronary Artery disease

In the NSTEMI group only around 9.6% patients have non-obstructive CAD

Mostly young

Mostly females

Percutaneous coronary intervention

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