Early Management of ACS - Presentation 92 slides According to latest ACC/AHA guidelines www.medicalgeek.com

1. Early Management of
Acute Coronary
Syndrome
Dr.Vitrag H. Shah
Second Year Resident
Medicine Dept.
GMC,Surat

2. 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).

3. 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.

4. 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transmural MI, and nontransmural MI, have been
replaced by STEMI and NSTEMI.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.

6. 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.

7. 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

8. CHARACTERISTICS OF TYPICAL ANGINAL CHEST PAIN
(ADAPTED FROM ROSEN’S EMERGENCY MEDICINE)
CHARACTERISTIC SUGGESTIVE OF ANGINA LESS SUGGESTIVE OF
ANGINA
TYPE OF PAIN DULL SHARP/STABBING
PRESSURE/CRUSHING
PAIN
DURATION 2-5 MIN, <20 MIN SECONDSTO
HOURS/CONTINUOUS
ONSET GRADUAL RAPID
LOCATION/CHEST WALL SUBSTERNAL, NOT LATERAL CHEST
TENDERNESS TENDER TO PALP. WALL/TENDER TO PALP.
REPRODUCIBALITY WITH WITH
EXERTION/ACTIVITY BREATHING/MOVING
AUTONOMIC SYMPTOMS PRESENT USUALLY ABSENT

10. • 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

11. 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.

13. 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 LCx/RCA
(Posterolateral/
Inferoposterior MI)
*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.

14. 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

15. 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.

16. 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.

17. 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.

19. 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).

21. 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.

22. 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

23. 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.

25. 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.

26. 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

27. 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.

28. 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

29. 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

30. 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.

31. 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.

32. 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

33. 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.

34. 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.

35. 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.

36. 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).

37. 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)

38. 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.

40. 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).

42. 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

43. 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
• .

45. 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.

46. 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.

47. 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

48. 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.

49. Contraindications

51. 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.

52. 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.

53. 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

54. 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

55. 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.

56. 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.

57. Angioplasty vs. Lytic Therapy

58. 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.

59. 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.

61. 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

62. 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.

63. 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.

64. 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

65. 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.

66. 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.

68. 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)

69. Fondaparinux
• The indirect Factor Xa inhibitor
• Equivalent for early efficacy compared with enoxaparin
• Lower risk of major bleeding.

70. 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

71. 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.

73. 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• ).

74. 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.

76. 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.

77. 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• ).

78. 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.

79. Invasive versus Conservative Strategy

80. 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.

85. 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.

86. 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.

87. 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.

88. 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.

89. 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)

90. 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.

91. 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)

92. Thank You