Early Management of

Acute Coronary

Syndrome

Dr.Vitrag H. Shah

Second Year Resident

Medicine Dept.

GMC,Surat

Introduction • The management of patients with acute

myocardial ischemia and infarction is one of the

few practices in critical care medicine that can

save lives on a continued basis, but only when

appropriate interventions are used early (often

within hours after the initial contact with the

patient).

• Those interventions are described in this slide

using information from practice guidelines

published by the American College of

Cardiology and American Heart Association

(ACC/AHA).

Spectrum of ACS

ST-segment elevation myocardial infarction (STEMI)

Non-ST-segment elevation myocardial infarction (Non-

STEMI)

Unstable Angina (UA)

Slient MI : More common in elderly and diabetic patients.

• The first condition (STEMI) is the result of complete and

sustained thrombotic coronary occlusion, while the last two

conditions (non-STEMI and UA) are the result of either

partial thrombotic coronary occlusion or transient complete

occlusion with spontaneous revascularization.

Terminology

• Electrocardiographic-pathologic correlations are far from

perfect and terms such as Q-wave MI, non-Q-wave MI,

transmural MI, and nontransmural MI, have been

replaced by STEMI and NSTEMI.

• Contemporary studies using MRI suggest that the

development of a Q wave on the ECG is more

dependent on the volume of infarcted tissue rather than

the transmurality of infarction.

Epidemiology

• The relative incidence of UA/NSTEMI compared to

STEMI appears to be increasing.

• More than one-third of patients with UA/NSTEMI are

women, while less than one-fourth of patients with

STEMI are women.

• Approximately six million persons per year in the United

States present to hospital emergency departments (EDs)

with a complaint of chest pain or other symptoms

suggestive of ACS. A diagnosis of an ACS is established

in 20 to 25% of such patients.

Defination Stable Angina Pectoris : Chest or arm discomfort that

may not be described as pain but is reproducibly

associated with physical exertion or stress and is

relieved within 5–10 minutes by rest and/or sublingual

nitroglycerin.

UA : Angina pectoris or equivalent ischemic discomfort

with at least one of three features:

• (1) it occurs at rest (or with minimal exertion), usually

lasting >10 minutes;

• (2) it is severe and of new onset (i.e., within the prior 4–6

weeks); and/or

• (3) it occurs with a crescendo pattern (i.e., distinctly

more severe, prolonged, or frequent than previously).

NSTEMI : UA + elevated cardiac biomarkers

CHARACTERISTICS OF TYPICAL ANGINAL CHEST PAIN

(ADAPTED FROM ROSEN’S EMERGENCY MEDICINE)

CHARACTERISTIC SUGGESTIVE OF ANGINA LESS SUGGESTIVE OF

ANGINA

TYPE OF PAIN DULL

PRESSURE/CRUSHING

PAIN

SHARP/STABBING

DURATION 2-5 MIN, <20 MIN SECONDSTO

HOURS/CONTINUOUS

ONSET GRADUAL RAPID

LOCATION/CHEST WALL

TENDERNESS

SUBSTERNAL, NOT

TENDER TO PALP.

LATERAL CHEST

WALL/TENDER TO PALP.

REPRODUCIBALITY WITH

EXERTION/ACTIVITY

WITH

BREATHING/MOVING

AUTONOMIC SYMPTOMS PRESENT USUALLY ABSENT

• The joint task force further refined the definition of MI by

developing a clinical classification according to the assumed

proximate cause of the myocardial ischemia:

• Type 1: MI consequent to a pathologic process in the wall of

the coronary artery (e.g. plaque erosion/rupture, fissuring, or

dissection)

• Type 2: MI consequent to increased oxygen demand or

decreased supply (e.g. coronary artery spasm, coronary

artery embolus, anemia, arrhythmias, hypertension or

hypotension)

• Type 3: Sudden unexpected cardiac death before blood

samples for biomarkers could be drawn or before their

appearance in the blood

• Type 4a: MI associated with PCI

• Type 4b: MI associated with stent thrombosis

• Type 5: MI associated with CABG

Cardiac Biomarkers

• Direct relationship between the degree of troponin

elevation and mortality.

• Both Trop-T & I are equivalent except in renal failure,

Trop-T is less sensitive. Trop-I is cheaper than Trop-T.

• However, in patients without a clear clinical history of

myocardial ischemia, minor troponin elevations have

been reported and can be caused by congestive heart

failure (CHF), myocarditis, or pulmonary embolism, or

they may be false-positive readings.

• Thus, in patients with an unclear history, small troponin

elevations may not be diagnostic of an ACS.

• A ratio (relative index) of CKMB mass: CK activity ≥ 2.5

suggests but is not diagnostic of a myocardial rather

than a skeletal muscle source for the CKMB elevation.

Role of ECG in ACS other than diagnosis

Leads Location of MI Infarct Related Artery

II, III, aVF Inferior wall of LV RCA/Dominant LCx

V1-V4* Anteroseptal wall of LV LAD

I, aVL, V5-V6/V4-V6 Lateral wall of LV Circumflex artery(LCx)

V4R (V3R-V6R) Right ventricle Proximal RCA

V7-V9** Posterior wall

(Posterolateral/

Inferoposterior MI)

LCx/RCA

*V1-V2: Ventricular septum.

V2-V4: Anterior wall of the LV. V2 overlaps the septum and anterior

wall.

V1-V3: Anteroseptal wall of the LV.

**V7is located at the left posterior axillary line

V8 at the tip of the left scapula

V9 at the left of the spinal column in the same horizontal plane

as V4-V6.

Inferior Wall MI due to RCA vs LCx

ECG RCA LCx

ST Elevation III > II II > III

T wave III > II II > III

Reciprocal ST depression aVL > I May be present in V2-

V3. I & aVL either

isoelectric or may be ST

elevation

V4R T wave upright T wave inversion

RVMI May occur in Proximal

RCA obstruction

-

Posterior MI - May occur

Posterior Wall MI

• Posterior MI can be confirmed by placing extra

electrodes in V7, V8, and V9

• Posterolateral MI: Occlusion of the LCx artery can cause

posterior, straight posterior, or posterolateral MI. It is

suspected in the 12-lead ECG when there is ST

depression in V1 to V3.

• Inferoposterior MI: ST elevation in leads II, III, and aVF

with ST depression in V1 to V3. Reciprocal ST

depression in V1-V3 indicates the presence of a

posterolateral MI. Tall R waves may develop in V1 or V2,

although this usually occurs much later several hours

after the acute episode.

Right Ventricular Myocardial Infarction

• RVMI is a common complication of acute inferior MI. If

the initial ECG confirms the diagnosis of acute inferior

MI, right-sided precordial leads should be recorded

immediately .

• Right sided precordial leads are recorded by

repositioning the precordial leads V3, V4, V5, and V6 to

the right side of the chest in the same standard location

as that on the left.

• Right-sided precordial leads are not routinely recorded if

there is no evidence of acute inferior MI.

Thrombolysis in Myocardial Infarction (TIMI)

Score

Other risk factors include diabetes mellitus, left ventricular dysfunction,

renal dysfunction and elevated levels of brain natriuretic peptides and

C-reactive protein.

Early Management of ACS (CCU)

• Coronary thrombosis is responsible for the tissue injury

in acute myocardial infarction led to the adoption of

several therapeutic measures designed to limit thrombus

formation and alleviate thrombotic obstruction.

• These measures include antiplatelet therapy (aspirin,

platelet glycoprotein inhibitors), anticoagulant therapy

(heparin), chemical dissolution of clots (fibrinolytic

agents), and mechanical disruption of clots (coronary

angioplasty).

Routine Measures : Relieving Chest Pain

Nitroglycerin

• Decreases myocardial oxygen demand (by

lowering preload) and increasing myocardial

oxygen supply (by dilating infarct-related coronary

vessels or collateral vessels)

• Nitroglycerin (0.3-0.6 mg sublingual tablets or

aerosol/buccal spray) is given for up to three

doses (each 5 minutes apart) to relieve chest

pain. If the pain subsides, intravenous

nitroglycerin can be started for continued pain

relief.

• If the chest pain persists after 3 doses of

nitroglycerin, immediate administration of

morphine is indicated.

Nitroglycerin • Intravenous nitroglycerin is also indicated for persistent or

recurrent chest pain due to unstable angina and for acute

coronary syndromes associated with hypertension or

pulmonary congestion. Start with 5-10 µg/min & may be

increased by 10 µg/min every 3-5min max upto 100-

200µg/min until symptoms are relieved or fall in SBP<100

mmhg.

• Caution/Contraindication:

• Right ventricular infarction (because of the risk of

hypotension - aggressive volume loading is needed in this

situation to counteract the venodilating effects of NTG)

• In patients who have taken a phosphodiesterase(PDE-5)

inhibitor for erectile dysfunction within the past 24 hours

(Because of risk of hypotension)

• IV Atrpine if idiosyncratic sudden marked hypotension

Morphine

• Drug of choice for chest pain that is refractory to

nitroglycerin

• The initial dose is usually 4 mg, given by slow

intravenous push (e.g., 1 mg/minute), and this can be

repeated every 5 to 10 minutes if necessary.

• It may lead to fall in blood pressure due to decrease in

sympathetic nervous system activity and is not a

pathologic process. A drop in blood pressure to

hypotensive levels usually indicates hypovolemia and

can be corrected by volume infusion & leg elevation.

Pressor agents should NEVER be used to correct

morphine-induced decrease in blood pressure.

Antiplatelet Therapy : Aspirin

• Chewable aspirin in a dose of 162 to 325 mg should be

given to all patients with ACS who have not taken aspirin

prior to presentation.

• Non-enteric-coated aspirin is preferred because of

enhanced buccal absorption. The initial aspirin dose

(162 to 325 mg) should be followed by a daily dose of 75

to 162 mg(Enteric/Non-Enteric coated) , which is

continued indefinitely.

• Aspirin causes irreversible inhibition of platelet

aggregation by inhibiting thromboxane production, and

aspirin therapy (either alone or in combination with

thrombolytic therapy) has been shown to reduce

mortality and decrease the rate of re-infarction.

• All NSAIDS should be discontinued except ASA.

Antiplatelet Therapy : Thienopyridines

• Irreversibly block surface receptors involved in ADP-

induced platelet aggregation. This mechanism of action

differs from that of aspirin, which means that the

antiplatelet effects of aspirin and the thienopyridines

are additive.

• The anti-platelet activity of the thienopyridines requires

drug activation in the liver, so these drugs are not

recommended in patients with liver failure.

• Available Drugs in this class: Ticlodipine, Clopidogrel,

Prasugrel

Clopidogrel

• Inactive prodrug that is converted into an active

metabolite

• The recommended dose of clopidogrel in ACS is 300-

600 mg initially, followed by 75 mg daily

• Clopidogrel seems to be preferred because of fewer side

effects

• Should certainly be continued along with aspirin for

atleast one year in patients with a drug-eluting stent.

Prasugrel

• More rapid onset, and higher level of platelet inhibition

than clopidogrel.

• Increased risk of major bleeding

• It has been used in ACS patients following angiography

in whom PCI is planned.

• 60 mg loading dose followed by 10 mg/d for up to 15

months

• Contraindicated in patients with prior stroke or transient

ischemic attack

Antiplatelet Therapy : Ticagrelor

• Reversible ADP inhibitor

• Approved by US FDA on July 20, 2011

• Initial 180mg loading dose (with 325 mg loading dose of

aspirin) f/b 90 mg bid, initiated 12 hours after loading

dose with low dose aspirin (75-100 mg/day)

• Continued for atleast 1 year in combination with aspirin

• Reduced mortality rate compared with clopidogrel

Antiplatelet Therapy : Aspirin & Clopidogrel

resistance

• "Aspirin resistance" has been noted in 5–10% of patients

and more frequently in patients treated with lower doses

of aspirin, but frequently has been related to

noncompliance.

• Up to one-third of patients have low response to

clopidogrel, and a substantial proportion of these are

related to a genetic variant of the cytochrome P450

system.

• Alternative agent should be used in such patients.

Beta-Receptor Blockade • Reduce cardiac work and decrease myocardial energy

requirements. Targeted to HR of 50-60 bpm.

• Limit infarct size, reduce risk of reinfarction & VF

• Early institution of beta-blocker therapy is recommended for

all patients with ACS who do not have a contraindication.

Usual contraindications

• Severe sinus bradycardia with heart rate < 40 bpm

• Second- or third-degree heart block

• Decompensated systolic heart failure

• Hypotension

• Reactive airways disease ( Relative contraindication)

• Also not advised for cocaine-induced myocardial infarction

because of the potential for aggravated coronary

vasospasm from unopposed a-receptor activity.

Beta-Receptor Blockade

• Oral beta blocker therapy is suitable for most cases of

ACS.Intravenous therapy is more appropriate for

patients with hypertension or troublesome

tachyarrhythmias.

• The agents used most often in clinical trials of ACS are

atenolol and metoprolol.(Both are selective Beta-1

Receptor antagonist)

Oral regimen

• Start with intravenous dose of 2.5 to 5 mg and repeat

every 5 minutes if needed to a total dose of 10 mg.

Fifteen minutes after the last IV dose, start oral therapy

with 50 mg every 6 hours for 48 hours, then 100 mg BID.

IV regimen

• Add 5 mg metoprolol to 50 mL D5W and infuse over 15

to 30 minutes every 6 hours

Angiotensin-Converting-Enzyme Inhibition • Vasodilators that reduce cardiac work and decrease

myocardial energy requirements & have an inhibitory effect

on the cardiac remodeling that occurs after coronary artery

reperfusion and contributes to post-MI heart failure.

• Oral therapy started in the first 24 hours after onset of ACS

provides a significant survival benefit in patients with

anterior MI and acute MI associated with symptomatic

heart failure, left ventricular dysfunction (LVEF <0.40) and

tachycardia.

• Contraindications to ACE inhibitor therapy include

hypotension, renal failure (creatinine >2.5 mg/dL), K+≥5.0

and bilateral renal artery stenosis.

• To minimize the risk of hypotension, only oral therapy is

recommended, and the starting dose is usually reduced

and then increased over the next 48 hours.

Angiotensin-Receptor Blockers

• Produce a survival benefit equivalent to ACE inhibitors

• ARBs are considered as a suitable alternative for

patients who do not tolerate ACE inhibitors.

• One example of a successful ARB regimen is oral

valsartan, 20 mg initially, then gradually increase to a

final dose of 160 mg twice daily by the end of the

hospitalization.

• The contraindications for ARBs are the same as those

mentioned previously for ACE inhibitors.

Statin

• Early administration of intensive statin therapy (e.g.,

atorvastatin 80 mg) prior to percutaneous coronary

intervention (PCI) has been shown to reduce

complications, suggesting that high-dose statin therapy

should be started at the time of admission.

Reperfusion Therapy

• In the early 1980s, two distinct modes of therapy were

introduced to alleviate thrombotic obstruction and restore

patency in occluded coronary arteries.

• Pharmacologic dissolution of blood clots using drugs that

stimulate fibrinolysis (thrombolytic therapy), and the

other involves the mechanical disruption of clots using

specialized balloon-tipped catheters (coronary

angioplasty).

Thrombolytic Therapy

• The first fibrinolytic agent studied was streptokinase.

• Survival benefit depends of Initial ECG, Timing ,

Selection of candidates, Fibrinolytic agent.

Available Drugs:

• Streptokinase (SK), Alteplase (tPA), Reteplase (rPA),

Tenectaplase (TNK)

Initial ECG

• The survival benefit of thrombolytic therapy is greatest

in patients who present with new-onset left bundle

branch block and ST-segment elevation in the

anterior precordial leads, while there is no survival

benefit in patients with ST-segment depression on

the initial ECG.

• So not useful in NSTEMI & UA.

Timing (Time lost is lives lost)

• The survival benefit of thrombolytic therapy is greatest

when therapy is initiated in the first few hours after the

onset of chest pain. Thereafter, the survival benefit

declines steadily with time and is negligible or lost

when the delay to initiation of therapy exceeds 12

hours.

• When a patient with sudden onset of chest pain enters

the emergency room, an electrocardiogram should be

performed and interpreted within the next 10 minutes

(door-to-ECG time <10 minutes).

• Thrombolytic therapy, if indicated, should be started

within 30 minutes after the patient enters the emergency

room (door-to-needle time <30 minutes).

Selection of Candidates

• Patients are candidates for thrombolytic therapy if

coronary angioplasty is not immediately available

and all of the following conditions are present:

(1) chest pain for at least 30 minutes but less than 12

hours

(2) a 12-lead ECG that shows ST elevation of 0.1 mV (1

mm) or more in two contiguous leads, or a new left

bundle branch block;

(3) the absence of hypotension or heart failure; and

(4) the absence of a contraindication to thrombolytic

therapy that would create an unacceptable risk of

bleeding

Thrombolytic therapy in Posterior wall MI

• The most recent ACC/AHA practice guidelines include

true posterior MI as a condition that might benefit from

thrombolytic therapy if treated within 12 hours of

symptom onset.

• This condition should be suspected when the ECG

shows ST-segment depression with upright T waves in

precordial leads V1 through V4 . The discovery of ST-

segment elevation in additional precordial leads V7 - V9

will help confirm the diagnosis of posterior wall MI

• .

Fibrinolytic Agents

• Act by converting plasminogen to plasmin, which then

breaks fibrin strands into smaller subunits. Some

(streptokinase) act on circulating plasminogen and

produce a systemic lytic state, while others (alteplase,

reteplase and tenecteplase) act only on plasminogen

that is bound to fibrin and produce clot-specific lysis.

• The site of action (clot-specific versus systemic) has

little clinical relevance.

Streptokinase (SK)

Bacterial protein

First thrombolytic agent evaluated in clinical trials

Least expensive

Least favored because it acts as an antigen and

produces fever (in 20 to 40% of cases), allergic reactions

(in 5% of cases), and accumulation of neutralizing

antibodies with repeated use

Because of the risk of an allergic reaction, patients

should not receive streptokinase if that agent had been

received within the preceding five days to two years.

Alteplase (tPA)

• Tissue plasminogen activator or tPA

• Molecular clone of an endogenous plasminogen

activator

• Does not produce allergic reactions

• Improved survival with alteplase compared to

streptokinase

Bolus Fibrinolytics : Reteplase & Tenecteplase

Reteplase (rTA):

• Molecular variant of tPA that is given in 2 bolus doses

30 minutes apart.

• It is easier to give than tPA and produces more rapid clot

lysis.

Tenecteplase (TNK-tPA)

• Another variant of tPA that is given as a single bolus. It

is the most clot-specific fibrinolytic agent and

produces the most rapid clot lysis.

Neither of these (tPA, rTA, TNK) attributes offers a

clinical advantage because no difference in the

incidence of life-threatening bleeding and no difference

in mortality rate but all of these are superior than SK.

Contraindications

Complications

Intracerebral hemorrhage (0.5-1.0%)

• May be more common with alteplase when compared to

streptokinase, but there is no difference between

alteplase, reteplase, and tenecteplase.

Extracranial bleeding that requires blood

transfusions occurs in 5 to 15% of patients, regardless

of the lytic agent used.

• There is no correlation between the risk of

hemorrhage and the degree of clot-specificity of the

fibrinolytic agents.

Hemorrhagic complications : Management

• Hemorrhagic complications of thrombolytic therapy are

the result of systemic fibrinolysis with depletion of

circulating fibrinogen levels.

• If necessary, cryoprecipitate (10 to 15 bags) can be used

to achieve a serum fibrinogen level of 1 g/L.

• If bleeding persists, fresh frozen plasma (up to 6 units)

can be administered, followed by platelet infusions (10

bags) if needed.

• The use of antifibrinolytic agents such as epsilon-

aminocaproic acid (5 grams given over 15 to 30 minutes)

is discouraged because these agents can produce

extensive thrombosis.

Reocclusion

• The benefit of thrombolytic therapy is limited by the risk

of reocclusion following clot lysis, which is reported in up

to 25% of cases.

• This may be a natural consequence of clot dissolution

because the exposed thrombin (which had been

enmeshed in the thrombus) has prothrombotic effects

via platelet activation and an increased rate of thrombin

formation .

• To counteract this process, antithrombotic therapy with

heparin and antiplatelet agents is given in combination

with thrombolytic therapy

Assessment by Angiography TIMI grading system:

• Grade 0: Complete occlusion of the infarct-related artery

• Grade 1: Some penetration of the contrast material

beyond the point of obstruction but without perfusion of

the distal coronary bed

• Grade 2: Perfusion of the entire infarct vessel into the

distal bed, but with flow is delayed compared with normal

• Grade 3: Full perfusion of infarct vessel with normal flow

TIMI frame count : Number of frames on the cine film

required for dye to flow from the origin of the infarct-

related artery to a landmark in the distal vascular bed

TIMI myocardial perfusion grade : Determining the rate of

entry and exit of contrast dye from the microvasculature

in the myocardial infarct zone

Coronary Angioplasty

• The use of balloon-tipped catheters to open occluded

arteries (balloon angioplasty) was adapted for use in

the coronary arteries in 1977 by a Swiss physician

named Andreas Gruntzig.

• Percutaneous coronary angioplasty is now the preferred

method of reperfusion therapy for patients with occlusive

coronary thrombosis.

Primary PCI

• PCI, usually angioplasty and/or stenting without

preceding fibrinolysis, referred to as Primary PCI.

• It appears to be more effective than fibrinolysis in

opening occluded coronary arteries and, when

performed by experienced operators [75 PCI cases (not

necessarily primary) per year] in dedicated medical

centers (36 primary PCI cases per year), is associated

with better short-term and long-term clinical outcomes.

• Compared with fibrinolysis, Primary PCI is generally

preferred when the diagnosis is in doubt, cardiogenic

shock is present, bleeding risk is increased, or

symptoms have been present for at least 2–3 h when the

clot is more mature and less easily lysed by fibrinolytic

drugs.

Angioplasty vs. Lytic Therapy

Timing • The beneficial effects of

coronary angioplasty, like those

of thrombolytic therapy, are

time-dependent.

• Angioplasty should be

performed within 90 minutes

after the patient arrives in the

emergency department .

• This, of course, only applies to

the use of angioplasty for

patients with ST-elevation MI

who present within 12 hours of

symptom onset.

Interhospital Transfer • The major limitation of coronary angioplasty is

availability. Less than 25% of hospitals in the United

States have facilities for coronary angioplasty, and in

Europe, fewer than 10% of hospitals have this capability.

The current recommendations for interhospital transfer

• If the symptom duration is less than 3 hours,

thrombolytic therapy is recommended unless

interhospital transfer will not add more than a one-hour

delay to treatment.

• If the symptom duration is longer than 3 hours,

interhospital transfer for angioplasty is

recommended. The total door-to-balloon time, including

the transfer time, should be close to 90 minutes to

achieve the optimal benefit of angioplasty.

Summary : Timing

• If patient presents within 12 hours:

• Door to ECG : 10min

• Door to Needle : 30min

• Door to Balloon : 90min

• Golder Hour : First 60 min

• Total Ischemic Time : Within 120 min

Class-I indications of CABG in NSTEMI

• Significant left main coronary artery stenosis.

• Left main equivalent disease, defined as ≥70 percent stenosis of the proximal

left anterior descending (LAD) and proximal left circumflex arteries.

• Ongoing ischemia that is not responsive to maximal nonsurgical therapy in

patients in whom revascularization with percutaneous coronary intervention is

suboptimal or not possible.

Class-I indications of CABG in STEMI

The following are indications for emergent or urgent CABG:

1. Failed percutaneous coronary intervention (PCI) with persistent pain or

hemodynamic instability if coronary anatomy is suitable for surgery.

2. Persistent or recurrent ischemia refractory to medical therapy if coronary

anatomy is suitable for surgery, a significant area of myocardium is at risk, and

the patient is not a candidate for PCI.

3. At the time of surgical repair of postinfarction ventricular septal rupture or

mitral regurgitation.

4. Cardiogenic shock in patients less than 75 years of age who develop shock

within 36 hours of MI and are suitable and appropriate candidates for

revascularization that can be performed within 18 hours of shock.

5. Life-threatening ventricular arrhythmias in the presence of at least 50 percent

left main stenosis and/or triple-vessel disease.

• If possible, an internal mammary artery graft should be used to bypass a

significantly stenosed left anterior descending artery.

Adjuncts to Reperfusion Therapy

• Antithrombotic therapy with antiplatelet agents and

heparin has a proven benefit when used with or without

reperfusion therapy.

• When added to reperfusion therapy (particularly

thrombolytic therapy), antithrombotic therapy can help to

prevent reocclusion and recurrent infarction.

LMWH/UFH , Fodaparinux

Bivalirudin

Aspirin

Platelet Glycoprotein Inhibitors

Heparin : UFH vs LMWH • Particularly advantageous in patients who receive

fibrinolytic agents to reduce the risk of reocclusion from

the prothrombotic effects of thrombin exposed during clot

dissolution.

LMWH is preferred to UFH for patients with unstable

angina (UA) and non-ST-segment elevation myocardial

infarction (non-STEMI).

UFH and LMWH are considered equivalent in patients

with ST-segment elevation myocardial infarction (STEMI)

who do not undergo reperfusion therapy.

Despite promising results with LMWH, UFH is

recommended for patients with STEMI who undergo

reperfusion therapy with fibrinolytic agents or

angioplasty.

Recommended Dose Regimens : LMWH Enoxaparin

• 0.6 ml = 60 mg

• Start with intravenous bolus of 30-40 mg, and follow with

subcutaneous injection of 1 mg/kg twice daily for 2-8

days (Usually 5 days). Max 100 mg for 1st two doses.

• Reduced dosing is necessary in renal insufficiency.

• Give Enoxaparin 15 min before or 30 min after

Fibrinolytic therapy.

• First SubQ dose should be administered with IV bous.

• Don’t give IV Bolus in patients of NSTEMI/UA & age >75

yrs.

• In patients >75 yrs, 0.75 mg/kg every 12 hours and Max

75 mg for 1st two doses.

Recommended Dose Regimens : UFH

UFH: Start with intravenous bolus of 60-70 Units/kg, and

follow with infusion of 12-15 Units/kg/hr.

UFH with fibrinolytic agents: Start with intravenous bolus

of 60 Units/kg (Max 4000U), and follow with infusion of 12

Units/kg/hr (Max 1000U/hr).

UFH with angioplasty:

• If not planning to use GPIIb/IIIa inhibitor, intravenous bolus of

70-100 Units/kg & 50-70 Units/kg if planning to use GPIIb/IIIa

inhibitor and follow with infusion of 12-15 Units/kg/hr.

• Adjust infusion to maintain activated partial thromboplastin

time (aPTT) at 1.5 to 2 times control.The aPTT should be

checked 3 hours after starting the infusion and 6 hours after

each dose adjustment. In addition, platelet levels should be

checked daily in all patients receiving heparin (because of

the risk of heparin-induced thrombocytopenia)

Fondaparinux

• The indirect Factor Xa inhibitor

• Equivalent for early efficacy compared with enoxaparin

• Lower risk of major bleeding.

Bivalirudin

• Direct thrombin inhibitor

• Similar in efficacy to either UFH or LMWH among

patients treated with a GP IIb/IIIa inhibitor

• Use of bivalirudin alone causes less bleeding than the

combination of heparin and a GP IIb/IIIa inhibitor in

patients with UA/NSTEMI undergoing catheterization

and/or PCI

Role of Warfarin

• Patients with an anterior location of the infarction, severe

LV dysfunction, heart failure, a history of embolism, two-

dimensional echocardiographic evidence of mural

thrombus, or atrial fibrillation are at increased risk of

systemic or pulmonary thromboembolism.

• Such individuals should receive full therapeutic levels of

anticoagulant therapy (LMWH or UFH) while

hospitalized, followed by at least three months of

warfarin therapy.

Platelet Glycoprotein Inhibitors

• Block platelet receptors involved in platelet aggregation.

• When platelets are activated, specialized glycoproteins

on the platelet surface (called IIb/IIIa receptors) change

configuration and begin to bind fibrinogen. When

fibrinogen molecules bind to adjacent platelets, platelet

aggregation occurs. The platelet glycoprotein (IIb/IIIa)

inhibitors bind to the surface receptors on platelets and

prevent the binding of fibrinogen. The result is inhibition

of platelet aggregation.

• The IIb/IIIa receptors are the final common pathway for

platelet aggregation, so the IIb/IIIa inhibitors are the most

powerful antiplatelet agents available (and are

sometimes called superaspirins•).

Drug Administration

• Abciximab, eptifibatide, and tirofiban –Given by IV infusion.

• Abciximab is a monoclonal antibody that is the most

potent, most expensive, and longest-acting drug in the

group. After discontinuing abciximab, bleeding times can

take 12 hours to normalize , and this prolonged action can

be a disadvantage when emergency bypass surgery is

contemplated.

• Eptifibatide (a synthetic peptide) and tirofiban (a tyrosine

derivative) are short-acting agents that are cleared by the

kidneys. After discontinuing these drugs, bleeding times

return to normal in 15 minutes for eptifibatide and 4 hours

for tirofiban. Dose adjustments in renal insufficiency are

recommended for both.

• Dose adjustments in renal failure are not necessary for

abciximab because it is an antibody and is presumably

cleared by the reticuloendothelial system.

Indications

• Primarily used in patients with UA & Non-STEMI when the

following conditions are present:

When coronary angioplasty is planned in the next 24 to 48

hours.

When there is evidence of continuing myocardial ischemia

(e.g., recurrent angina or angina at rest with transient ST-

segment changes).

When there are risk factors for recurrent ischemic events,

such as age >75 years, heart failure, new or worsening

mitral regurgitation, markedly elevated cardiac troponin

levels, and cardiogenic shock.

Indications

• Greatest benefits occur when these agents are used in

conjunction with angioplasty.

• Abciximab is recommended only when angioplasty is

planned. In the cath lab, the initial bolus of abciximab is

given after the arterial sheath is placed, and the

abciximab infusion is continued for 12 hours after the

procedure.

• Gaining popularity in patients with STEMI and are

usually given in combination with angioplasty or

thrombolytic therapy.

• In the future, expect platelet glycoprotein inhibitors to be

combined with low-dose fibrinolytic agents as a prelude

to coronary angioplasty (so-called Facilitated

Angioplasty•).

Adverse Effects & Contraindications

• Bleeding : The incidence of bleeding from these agents

is difficult to assess because they are often used in

combination with aspirin and heparin.

• Most of the bleeding is mucocutaneous, and

intracranial hemorrhage is not a risk with these agents.

• Thrombocytopenia : up to 2% of patients

• Active bleeding is an absolute contraindication while

Relative contraindications include major surgery within

the past 3 months, stroke in the past 6 months, systolic

blood pressure >180 mm Hg or diastolic pressure >110

mm Hg, and severe thrombocytopenia.

Invasive versus Conservative Strategy

Invasive versus Conservative Strategy

• In high risk patients, following treatment with anti-

ischemic and antithrombotic agents, coronary

arteriography is carried out within 48 h of admission,

followed by coronary revascularization (PCI or coronary

artery bypass grafting), depending on the coronary

anatomy.

• In low-risk patients, anti-ischemic and antithrombotic

therapy followed by "watchful waiting," and in which

coronary arteriography is carried out only if rest pain or

ST-segment changes recur or there is evidence of

ischemia on a stress test.

Hospital Phase Management : Activity

• Bed rest for the first 12 h

• In the absence of complications, resume an upright

posture by dangling their feet over the side of the bed

and sitting in a chair within the first 24 h. This practice is

psychologically beneficial and usually results in a

reduction in the pulmonary capillary wedge pressure.

• In the absence of hypotension & other complications, by

the 2nd or 3rd day, patients typically are ambulating in

their room with increasing duration and frequency, and

they may shower or stand at the sink to bathe.

• By day 3 after infarction, patients should be increasing

their ambulation progressively to a goal of 185 m (600 ft)

at least 3 times a day.

Hospital Phase Management : Diet

• Because of the risk of emesis and aspiration soon after

STEMI, patients should receive either nothing or only

clear liquids by mouth for the first 4–12 h.

• The typical coronary care unit diet should provide ≤ 30%

of total calories as fat and have a cholesterol content of

≤300 mg/d.

• Complex carbohydrates should make up 50–55% of total

calories.

• Portions should not be unusually large, and the menu

should be enriched with foods that are high in potassium,

magnesium, and fiber, but low in sodium.

Hospital Phase Management : Bowel Management

• Bed rest and the effect of the narcotics used for the relief

of pain often lead to constipation.

• A bedside commode rather than a bedpan, a diet rich in

bulk, and the routine use of a stool softener such as

dioctyl sodium sulfosuccinate (200 mg/d) are

recommended.

• If the patient remains constipated despite these

measures, a laxative can be prescribed.

Hospital Phase Management : Sedation

• Diazepam (5 mg), oxazepam (15–30 mg), or lorazepam

(0.5–2 mg), given 3–4 times daily, is usually effective.

• An additional dose may be given at night to ensure

adequate sleep.

• Specially important during the first few days in the CCU,

where the atmosphere of 24-h vigilance may interfere

with the patient's sleep.

• However, sedation is no substitute for reassuring, quiet

surroundings.

Prescription on discharge

Drug Duration/Indication

Aspirin + Clopidogrel/Other Atleast 1 year

Aspirin Lifelong

Betablockers Atleast 2 years

ACE inhibitors Lifelong if CHF, EF ≤ 40%, Large wall

motion abnormality, recurrent ischemic

events & Diabetes

Nitroglycerin In CHF* after MI, SOS if chest pain

Statins Highdose atleast for initial 30days and

then according to lipid profile

Sedatives SOS if sleep disturbance/anxiety

Warfarin As described earlier

* Preffered over diuretics (as Nitrates decrease preload without

decreasing plasma volume, so no risk of decreasing coronary perfusion)

Solving Myth : MI due to Hypoxia or Clot??

• The discovery that acute MI is the result of blood clots

that obstruct coronary arteries disputes the traditional

teaching that myocardial infarction is the result of a

generalized imbalance between myocardial O2 delivery

and O2 consumption. This distinction is important

because the O2-imbalance paradigm is the basis for the

overzealous use of oxygen breathing and blood

transfusions in patients with coronary artery disease.

• Blood clots (from ruptured atherosclerotic plaques)

cause heart attacks, not hypoxia or anemia.

• If you have ever wondered why heart attacks are

uncommon in patients with progressive shock and

multiorgan failure, you now have the answer.

Refereces:

American Heart Association & American College of

Cardiology Guidelines (http://www.cardiosource.org)

THE ICU Book, 3rd Edition - Paul L. Marino

Harrison’s PRINCIPLES OF INTERNAL MEDICINE :

Eighteenth Edition

Basic and Bedside Electrocardiography, 1st Edition -

Baltazar, Romulo F.

Braunwald's Heart Disease : A Textbook of

Cardiovascular Medicine : Ninth Edition

Washington Manual of Critical Care : 2nd Edition

UpToDate (http://www.uptodate.com)

eMedicine (http://www.emedicine.com)

Thank You