Ischemic Heart Disease
(IHD): Angina Pectoris
 Angina pectoris is the collection of symptoms
resulting from myocardial ischemia as a result
of atherosclerosis of coronary arteries
 IHD is also called coronary artery disease
(CAD) or coronary heart disease (CHD)
 CHD includes together with angina, acute
coronary syndrome (ACS)
 ACS comprises unstable angina (USA), acute
myocardial infarction (MI), acute HF, and
sudden death
1
Features of Angina Pain
 Location: Over the sternum or near to it, Small
area of chest (≤3 cm), entire right/left side, leg pain
 Radiation to left shoulder/arm, jaw, tongue, teeth
 Duration: Ranges from seconds to hours
 Descriptors: Sharp, sticking, stabbing, knifelike,
pricking, gas
 Triggers: Exercise, heavy meals, body position,
cold weather
 Nitroglycerin relief: after 45 seconds-5 min
 ECG: ST-depression, T-wave inversion
2
Causes of Angina Pectoris
 Typical angina results from advanced coronary
atherosclerosis in at least one moderately sized
epicardial coronary artery
 In general, obstructions in diameter of 60% or greater
are likely to be associated with angina, whereas lesions
of less than 50% ordinarily do not cause ischemia
 Severe angina (chest pain caused by little exertion) is
usually associated with coronary obstructions of 80% to
100%
 Patients are often characterized as having one-, two-, or
three-vessel disease, as determined by coronary
arteriography
3
Causes of Angina Pectoris
A,
Several high-grade narrowing of a
right coronary artery.
B, Severe (>90%) stenosis (arrows) of a
left anterior descending coronary artery
4
Coronary Stenosis
 Coronary artery obstructions are capable of changing
caliber,
 Constriction or narrowing of a preexisting lesion can be a
factor in precipitating angina and myocardial ischemia
Eccentric
Concentric
Nitrates
5
Risk Factors for Coronary
Artey Disease
Modifiable CAD Risk Factors
Causative Risk Factors (directly
associated with CAD development)
Non-modifiable CAD Risk Factors
o Cigarette smoking
o Hypertension
o Kidney disease
o Diabetes mellitus (Type-1 & 2)
o Elevated LDL & Reduced HDL
Predisposing Risk factors (Direct Impact
on Causative RF Development)
2
Obesity (BMI? 25 kg/m )
Physical inactivity
Socioeconomic factors
Age:
Males > 45 years
Females > 55 years
Male Gender
Family history of coronary artery disease
6
Non-standard CAD Risk
Factor
Non-standard CAD Risk Factor
Lipoprotein(a)


Homocysteine



Significance
Lp(a) is a cholesterol-rich
plasma lipoprotein with a
structure very similar to low
density lipoprotein
Increased levels of Lp(a) are
associated with high risk for
atherothrombotic cardiovascular
disease.
Homocysteine is sulphur
containing amino acid and is
derived from dietary methionine.
Hyperhomocysteinemia is a risk
factor for development of
cardiovascular disease.
It is associated with other
cardiovascular risk factors like
male gender, old age, smoking,
high blood pressure, elevated
cholesterol and lack of exercise. 7
AHA/ACC Guidelines for the Secondary
Prevention for Patients with Coronary and
Other Atherosclerotic Vascular Disease
Risk Factor
Intervention & Goal
Smoking
Complete cessation
Blood Pressure
<140/90 mm Hg & <130/80 mm Hg in diabetics &
kidney disease
Lipid Metabolism
LDL-C <100 mg/dL, If triglycerides >200 mg/dL,
non–HDL-C should be <130 mg/dL
Diabetes
Hemoglobin A1C <7%
Physical activity
At least 30 min of moderate intensity aerobic
activity (e.g., brisk walking) for minimum of 5
days/wk
Body Weight
BMI between 18.5–24.9 kg/m2
Waist circumference men <40 in, women <35 in
Influenza
vaccination
Patients with CAD should have an annual
influenza vaccination
8
Myocardial Oxygen Supply & Demand
Oxygen
Supply
•Coronary Blood Flow
•Oxygen Extraction &
Saturation
Oxygen
Demand
•Cardiac Contractility/Rate
•Ventricular Wall Tension
(Systolic & Diastolic)
9
Treatment Overview
 Medical management should be individualized
 Risk factor modification is indispensible for
prevention & treatment of CHD
 Goal of therapy: reduction of the number, severity,
& duration of anginal attacks
 Six drug classes are used alone/ in combinations:
o Nitrates
o β-blockers
o Calcium channel blockers
o Antiplatelets, Anticoagulants
o ACE inhibitors
10
Diagnostic Procedures
 Exercise tolerance test: ECG signs of
ischemia, angina
• HR-SBP product is usually used
 Myocardial imaging, echocardiographic or
nuclear, preferred to exercise tolerance
• Pharmacologic stress (e.g, dobutamine or
adenosine injection) can be used
 Cardiac catheterization & subsequent
angiography can detect coronary artery
spasm
11
Anti-Ischemic Drug Therapy
NITRATES
 Treatment of all anginal syndromes
 Mechanism & Properties:
 Inhibition of thromboxane synthase
 Venodilation is more than arterial because the latter
needs higher plasma nitrate level
 NO production→ + vascular SM –SH groups → Snitrothiols → Activation of Guanylate cyclase →
Increased intracellular cGMP
 Venous dilation →lowered preload →reduction of
ventricular filling pressure →decreased myocardial
O2 consumption → anginal pain relief
12
NITRATES
 Coronary artery vasodilation → increased
coronary blood flow increased oxygen supply
 Angiographic studies showed that coronary
arteries with eccentric atherosclelerotic lesion will
dilate in response to nitrates
 Another antianginal agent (ß-blocker or CCB)
must provide the antianginal effect during the
nitrate-free period
13
Short-Acting Nitrates
Sublingual Nitroglycerin (NTG)
 Dose: mostly 0.4 mg, relief of pain, objective hemodynamic



o
o
o
o
o
effect (10 mm Hg drop, ↑HR)
Onset: 1-3 min, duration:10-30
Prevention of attack: To be taken 5-10 min before the
exertion that possibly precipitate angina
Instructions to Patient:
Sit immediately, place NTG tablet under tongue
Max three tablets over 15 min
If pain persists >30 min →suspected MI
NTG tablets are volatile →a tablet left outside loses activity
in min
14
An open bottle →use for 6-12 months
Nitroglycerin Lingual Spray
 NTG lingual spray, 0.4 mg/metered dose is an
alternative for SL NTG
 Each canister has 200 metered dose/3 years
shelf-life
 Spray a single dose under or onto the tongue
 NTG lingual spray should not be inhaled
 Max dose: three sprays over 15 min
15
Long-Acting Nitrates
o NTG: SR capsule, Topical ointment, transdermal
patches
o Isosorbide Dinitrate (ISDN): oral, SR, SL, and
chewable
o Isosorbide Mononitrate (ISMN): SR tab, rapidrelease tablets
Long-acting nitrates are the prevention corner stone
therapy of all types angina
 CCB can be an alternative especially if angina
patient has improperly controlled HTN
16
Side Effects to Nitrates
 Hypotension
 Headache: tolerance develops after few weeks
 Dizziness
 Syncope/fainting necessitates dosage reduction
o Severe hypotension & bradycardia caused cardiac
arrest in patients experiencing MI
o NTG-induced vaso-vagal response → NTG
syncope → leg elevation, atropine, fluids
 Met-Hbemia is important when large IV NTG
doses used
17
Nitrate Tolerance
 Tolerance is unlikely to occur with NTG (SL, oral
spray), and SL isosorbide dinitrate
 Tolerance is likely with long-acting oral nitrates
(ISMN) & transdermal patches
 12 hour NTG transdermal patches’ intermittent
therapy minimize tolerance
 Intravenous NTG used in unstable angina (USA)
& severe HF is associated with tolerance
 12 hour intermittent intravenous NTG limit
nitrate tolerance
18
Nitrate Tolerance
Minimization
 Nitrate-free interval of 10-12 hours minimize
tolerance to therapeutic activity
 Lowest effective nitrate dose lower
tolerance
 ß-blocker or CCB is given to provide
anginal protection during nitrate-free period
 Long-acting nitrates have no evidence of
causing tolerance to SL nitrates’ use
19
MECHANISM OF Nitrate
Tolerance
 Depletion of vascular –SH groups, plasma volume
expansion, neurohormonal activation
 Nitrates increases superoxide anion (O2-) + NO →
peroxynitrite producing:
• Decreased endothelial NO production
• Increased sympathetic & RAA systems
• Increased vasoconstrictor responsiveness
• Peroxynitrite-dependent assumption stimulates the
question: dose nitrate have long-term detrimental
effects?
20
ISOSORBIDE DINITRATE &
MONONITRATE (ISDN & ISMN)
 ISDN oral formulation is used usually three times
a day especially in severe angina
 Usually ISDN is taken at 7 AM, Noon & 5 PM to
allow 12 hr nitrate-free period
 ISDN can be given twice/day in moderate
severity angina
 Isosorbide mononitrate (ISMN) can be given
once or twice/day (early morning & 7 hrs later)
 ISMN has better patient compliance
21
ß-ADRENERGIC BLOCKERS
 Decreased myocardial oxygen consumption by
lowering adrenergic-related HR, BP & contractility
 ß2-adrenergic receptors were shown to be present
in the heart by 10-40%, possibly augment cardiac
contractility & HR
 In chronic angina: ß-blockers should be given
before nitrates & CCBs
 ß-blockers are more effective than the other two
agents in lowering incidence of anginal episodes
 The three classes are similar in mortality reduction
 They lower CV morbidity/mortality in HTN, HF, or
MI patients
22
ß-ADRENERGIC BLOCKERS
THERAPEUTIC ENDPOINT
 Anginal attacks frequency & NTG consumption
are indices for therapeutic efficiency of antianginals
 Reduction in resting HR is best monitored to adjust
ß-blockers’ dose
 Dose can be increased till HR is 55 b/min, even 50
b/min is acceptable for asymptomatic patients
 ß-blockers with ISA do not lower resting HR
 Exercise testing is the best, though least practical:
 Reduction of exercise ST-depression
 HR-SBP product usually decreases (lowered wall
tension & HR)
23
β-Adrenergic Blockers
Dosing
 β-blocker pharmacodynamic actions are longer
than their plasma half-lives
 Usually taken once to twice daily for angina
 Atenolol t1/2 is 10 hours but clinical evidence
support the effectiveness of once daily regimen
 Propranolol is of short 2-3 hrs t1/2, yet its BP/HR
lowering effects are pronounced for 12 hours
 Clinical evidence support the effectiveness of
twice daily regimen of propranolol
24
β-Adrenergic Blockers
Cardio-selective & Contraindications
 Cardio-selective ß-blockers did NOT produce
adverse respiratory effects in moderate respiratory
diseases (Meta-analysis)
 Cardio-selective ß-blockers low inhibition of ß2induced peripheral vasodilation (α-vasoconstrictn)
• Atenolol/acebutalol/metoprolol preferred in
peripheral vascular disease & Raynaude’s disease
 DIABETES is NOT a contraindication for ß-blockers
• Lower mortality in diabetics after MI
• CAD is more severe in diabetics & has worse
prognosis over that developed in non-diabbetics
25
β-Adrenergic Blockers
 ISA ß-blockers→less effect on lipid/glucose
 ISA ß-blockers→ less bradycardia →less effective
in angina or worsen angina (better avoided)
 ß-blockers abrupt withdrawal can be serious in
severe atherosclerosis/USA →severe CV
effects like acute MI & sudden cardiac death
 ß-blockers withdrawal schedule can be a twoweeks four-steps on 2-3 days schedule
26
CALCIUM CHANNEL BLOCKERS
 Amlodipine & felodipine (DHPs) are the only
CCBs that can be used in HF patients
 Nifedipine IR, diltiazem & verapamil should be
avoided in HF patients
 INDICATIONS: Vasospastic & classical exertional
angina
 CCBs by arterial dilation →decrease myocardial
O2 demand
 CCBs cause coronary dilation Coronary →
increase myocardial O2 supply
 Vasospasm can occur at atherosclerotic site,
CCB can cause dilation
27
CALCIUM CHANNEL BLOCKERS
 NIFEDIPINE: 10% nifedipine patients experience
angina worsening because of powerful dilation→
reflex increase in HR → increase O2 demand →
can cause acute MI
 This is frequent with IR preparations
 IR nifedipine no longer used for any disease
 SR nifedipine is used
 Side Effects: hypotension, dizziness (15%), facial
flushing & headache & nausea
 Peripheral edema with DHPs
 Constipation with verapamil
28
CALCIUM CHANNEL BLOCKERS
contraindications
 Severe hypotension
 Severe aortic stenosis
 Extreme bradycardia
 Moderate to severe HF
 Cardiogenic shock
 Sick sinus syndrome
 Second/third degree A-V block
29
COMBINATION THERAPY
 ß-blockers-nitrate-CCB triple therapy is an
option to maximize benefit & lower side effects
 Disadvantages: Cost, possible additive side
effects (HF worsening by ß-blocker-CCB)
 Excessive vasodilation-bradycardia in triple
therapy can be minimized using CCB with less
potent vasodilating properties
 Initial therapy in chronic angina: ß-blocker
 Then Nitrate or CCB is added according to patient
status (No fixed guidelines)
30
COMBINATION THERAPY
 Nitrates, as a second class, are preferred in
patients with LV dysfunction
 CCBs, as a second class, are preferred whenever
further BP control is needed
 Two CCBs combination: Nifedipine with
verapamil or diltiazem lower dizziness & effects on
cardiac conduction & contractility
 Two CCBs combination used when standard triple
therapy (at max tolerable individual doses) is still
ineffective
31
Ranolazine (FDA Approval 2006)
Mechanism of Action
 Unlike traditional antianginal agents, it does not have
any appreciable effects on heart rate, arterial
resistance vessels, the myocardial inotropicity, or
coronary blood flow
 It does NOT affect blood pressure or heart rate
 Ranolazine does not affect myocardial oxygen supply
or demand
 Early preclinical work showed that it inhibits fatty acid
oxidation, however, at higher plasma level than those
used therapeutically
32
Ranolazine (FDA Approval 2006)
Mechanism of Action
 It is now known that ranolazine's anti-
ischemic effects are modulated through
inhibition of the late sodium current (INa)
 By inhibiting late sodium entry, and hence
calcium overload during ischemia
33
Ranolazine (FDA Approval 2006)
Mechanism of Action
 Ranolazine effectively inhibits the
consequences of ischemia as decreased
microvascular perfusion, as well as increased
myocardial oxygen demand
 This novel mechanism of action offers the
possibility of complementary effects when
added to more traditional antianginal agents
which act through their hemodynamic actions
34
Vasculoprotective
Drug Therapy
35
Rationale for CONVERTING
ANGIOTENSIN ENZYME INHIBITORS
 ACEIs reduced MI by 23% in HF patients → Are
ACEIs beneficial in LV dysfunction-free CAD
patients and post-acute MI patients?
The HOPE study:
 9,297 patients with chronic CAD and no HF
 Ramipril reduced incidence of death, MI, stroke,
need for revascularization, and angina worsening
 Benefit was independent of BP lowering effect
 Patients were on standard angina therapy
36
CONVERTING ANGIOTENSIN
ENZYME INHIBITORS
EUROPA study: 12,218 PATIENTS, 4.2 YEARS
o Perindopril in stable angina with no HF
o Reduction of combined incidence CV death, MI &
cardiac arrest
o Similar to HOPE study, is this beneficial effect
class-related?
o Tissue binding & inhibition of ACE in myocardium
& endothelium varies among different ACEIs
For ARBs, there is no clinical trials yet
37
Antiplatelet Therapy
Aspirin
 Platelet activation produces coronary occlusion either by
formation of a platelet plug or through release of
vasoactive compounds from the platelets
 A single 100-mg aspirin dose virtually eliminates
thromboxane A2 production, whereas doses below 100
mg result in a dose-dependent reduction in thromboxane
A2 synthesis
 Determine the effect of aspirin doses on the TXA2 to PGI2
 Selective inhibition of platelet-generated TXA2 synthesis
has been shown with 75 mg of controlled-release aspirin
daily
38
Aspirin
 It has been believed that higher doses of aspirin
would produce a higher level of efficacy than
low doses
 However, all available literature indicates that
low dosages of aspirin (75–325 mg/day) are as
effective as higher dosages (625–1,300
mg/day) in the treatment of angina
 Therefore, current guidelines recommend a
daily dosage of 75 to 162 mg orally for the
prevention of MI and death in patients with CAD
39
Clopidogrel
 Clopidogrel (Plavix), a thienopydridine, inhibits platelet
function in vivo via noncompetitive antagonist of the
platelet ADP receptor
 Clopidogrel at a dosage of 75 mg orally every day was
demonstrated in one study to be slightly more effective
than aspirin in the secondary prevention of MI and death
in patients with various manifestations of atherosclerotic
vascular disease
 Clopidogrel historically was to serve as an alternative
antiplatelet agent in patients with a true contraindication
to aspirin
40
Clopidogrel
 The magnitude of difference in benefit seen
with clopidogrel was quite small and not
sufficient to justify its broad scale use in the
treatment of CAD
 Based on this study, the role of clopidogrel
historically was to serve as an alternative
antiplatelet agent in patients with a true
contraindication to aspirin
41
Aspirin/Clopidogrel
Combination
 The combination of aspirin and clopidogrel was compared
with aspirin alone in patients with acute coronary
syndromes without ST-segment elevation in the CURE
study for an average of 9 months
 The combination of aspirin and clopidogrel significantly
reduced CVS death, nonfatal MI, or stroke
 The results of the CURE study were confirmed in the
Clopidogrel for Results of Events During Observation
(CREDO) trial where patients with ACS who were treated
with percutaneous coronary stent intervention received
aspirin/clopidogrel for 1 year
 Patients receiving both aspirin and clopidogrel for 1 year
42
had a lower incidence of death, MI, and stroke in
comparison to patients who only received aspirin
Aspirin/Clopidogrel
Combination in Chronic CAD
 Given the beneficial effects seen in patients with recent
ACS, and in patients with PCI plus stent placement
 Is dual therapy with aspirin plus clopidogrel would be
superior to aspirin in the treatment of chronic stable CAD
 In the Clopidogrel for High Atherothrombotic Risk and
Ischemic Stabilization, Management, and Avoidance
(CHARISMA) trial, 15,063 patients with documented
vascular disease (CAD, cerebrovascular, peripheral
arterial disease), or no documented vascular disease but
with multiple cardiovascular risk factors, were assigned
to aspirin alone or aspirin plus clopidogrel for an average
of 28 months duration
43
Aspirin/Clopidogrel
Combination in Chronic CAD
 Unlike the results from ACS studies, however,
the combination of aspirin plus clopidogrel did
NOTreduce the incidence of the primary
endpoint (risk of death, MI, stroke, or
coronary revascularization) as compared with
aspirin alone
 In a secondary analysis of patients who
entered the trial with documented vascular
disease, dual therapy did produce statistically
significant reductions in the primary endpoint
as compared with aspirin
44
VARIANT ANGINA (CORONARY
ARTERY SPASM)
 ST-segment elevation is the cardinal mark for
variant angina
 It results from severe large coronary artery
segmental spasm with transient total occlusion
 Transient arrhythmias & conduction disturbances
may be observed during pain or no symptoms
 ↑ HR-SBP product characterizing stable angina
during pain does not occur with variant angina
 Angiography can show the vasospasm
 Ergonovine test can provoke the unpredictable
coronry vasospasm by stimulating α-adrenergic &
5-HT receptors
45
VARIANT ANGINA therapy
 CCBs are usually preferred over nitrates or ß-
blockers
 All CCBs are equally effective but intrinsically
long-acting or SR forms are preferred
 CCB-Nitrate combination should be tried when
max CCB dose is still ineffective
 Aspirin is indicated for variant angina
 ß-blockers mostly worsen variant angina by
unmasking α-vasoconstriction by ß2-blockade
 Cardioselective ß-blockers can worsen variant
angina
46
VARIANT ANGINA therapy
Prognosis
 50% of variant angina patients undergo full
spontaneous recovery via unknown mechanism
 This occurs with isolated vasospasm without
atherosclerosis (short-duration symptoms)
 Therapy can be stopped, after gradual tapering, if
patients are free from pain, significant arrhythmias,
or silent ischemic episodes for one year
 Risk factor modification may enhance variant
angina remission
47
VARIANT ANGINA therapy
Development of mi
 Variant angina can proceed to MI or myocardial
death especially in multi-vessel coronary spasm
 In a small group of hospitalized variant angina
patients, 76% experienced morbid cardiac events
(acute MI, sudden death, & CA bypass graft)
within a month of angina onset
 Aggressive CCB+NTG infusion during the early
stages improve prognosis
48
Acute Coronary syndrome
(ACS)
49
50
UA/NSTEMI Goal of Therapy
 Prevent total occlusion of the infarct-related
artery
 (a) Glycoprotein (GP) IIb/IIIa inhibitors, other
antiplatelet agents, and anticoagulants
 (b) Percutaneous coronary intervention (PCI)
can be either or both:
 (1) Percutaneous transluminal coronary
angioplasty, (i.e., “balloon”)
 (2) Stent implantation
51
Unstable Angina Initial
Treatment
“MONA” (MOrphiNe, OxygeN,
 Hospitalization, bed NTG)
rest, & treatment of underlying
predisposing factors (HTN, infection, HF,
arrhythmias) are indispensable
 Pharmacologic strategy aims to reduce ischemia &
inhibit thrombotic process
 ß-blockers must be acutely administered to
prevent the progression to MI & death initialy by IV
route, then orally
 Nitrates both SL & then intravenously for pain
relief & ischemia reduction
 CCBs can reduce ischemia bur should be
reserved to ß-blockers resistant patients
52
Unstable Angina Treatment
Antiplatelets
 Chewable aspirin (325 mg dose) should be administered to
all patients as they prevented progression to MI & death
 Aspirin (81-325 mg/day) & clopidogrel (300 mg load, 75
mg PO) combination acutely & up to 1 year has been
shown to decrease risk of CV death, MI & stroke in
USA/NSTEMI patients
 Patients with USA/NSTEMI receiving aspirin & undergoing
PCI, clopidogrel should be given prior to the procedure
followed by 1-12 months treatment
 Patients undergoing CABG, clopidogrel should be
discontinued for 5-7 days before procedure
53
Unstable Angina Treatment
 Antithrombin: UFH & LMWHs were found to be
equivalent as regards improving clinical outcomes
in USA/NSTEMI patients
• Enoxaparin, recommended by ACC/AHA, shown
to be superior to UFH in preventing CV events
 GP IIb/IIa receptor antagonists, in addition to
aspirin & UFH/LMWH, decreased composite risk
death, MI, urgent revascularization in patients
USA/NSTEMI: Eptifibatide and tirofiban
 Abciximab is NOT approved for UA/NSTEMI
medical management unless PCI is planned within
24 hrs
54
Revascularization: Percutaneous
Coronary Intervention
 Percutaneous coronary intervention (PCI), also known
as angioplasty, involves the percutaneous insertion of a
balloon catheter into the femoral artery in a similar
fashion to angiography
 Stents can be of the bare metal (BMS) variety, or
contain a drug impregnated on the surface of the stent to
prevent re-stenosis (drug-eluting stent or DES)
55
Revascularization: Percutaneous
Coronary Intervention
 Mechanical disruption of the atherosclerotic plaques and
exposure of plaque contents to the bloodstream during
PCI, can cause acute thrombotic events likee MI & death
 Potent antiplatelet and antithrombotic strategies are
needed to prevent such reactions
 Initially, strategies involved the use of high-dose
unfractionated heparin and aspirin
 Current strategies involve the administration of aspirin,
clopidogrel, an antithrombin agent, as well as a
glycoprotein (Gp) IIb/IIIa receptor antagonist in
selected patients
56
Antiplatelets in
Revascularization
 In patients who are NOT on daily aspirin, 325 mg
aspirin should be initiated 2 hrs before procrdure
 A 600 mg clopidogrel loading dose on or before
the procedure is recommended, producing
antiplatelet action within 2 hours
 GPIIb/IIIa receptor antagonists improve outcomes
in patients undergoing PCI as well as UA/NSTEMI
patients medical management
 These agents, when administered IV during PCI and
for 12 to 24 hours afterward, significantly decrease
the risk of death, acute MI, or need for repeat PCI
57
Indications and Dosing of Glycoprotein
IIb/IIIc Receptor Antagonists
Indication
Abciximab
Eptifibatide
Percutaneous
transluminal
coronary
angioplasty
(PCTA)
0.25 mg/kg IV
bolus, then
0.125
mcg/kg/min IV
infusion × 12
hr
180 mcg/kg IV bolus,
Not approved use
then 2.0 mcg/kg/min IV
× 20–24 hr
Repeat 180 mcg/kg IV
bolus 10 mins after first
bolus
Coronary stent
placement
0.25 mg/kg IV Same as above
bolus, then
0.125
mcg/kg/min IV
infusion×12 hr
Acute coronary
Not approved
syndrome
use
(unstable angina
and non–STEMI)
180 mcg/kg IV bolus,
then 2.0 mcg/kg/min IV
× 20–24 hr
Tirofiban
Not approved use
0.4 mcg/kg/min IV
load × 30 mins, then
0.1 mcg/kg/min IV
infusion × 48–102 hr
58
Use of GpIIb/IIIa Antagonists
in UA/NSTEMI
 The Gp IIb/IIIa receptor antagonists currently are
recommended as options in patients with
USA/NSTEMI in one of the following groups:
 in whom catheterization and PCI is planned
 who have continuing ischemia despite treatment
with aspirin, UFH/ LMWH/ fondaparinux/
bivalirudin, nitrates, β-blockers, and clopidogrel
 Patients have other high risk features, such as
elevated troponin or ST-segment changes on the
initial ECG
59
Antithrombin Therapy &
Revascularization
 Unfractionated heparin (UFH), LMWH enoxaparin
and the direct thrombin inhibitir bivalirudin are
options for administration at the time of the
procedure
 They are discontinued after PCI procedure unless
a compelling indication exists
 They are used in the following:
 ACS: Medical management
 PCI: Therapy initiated at time of procedure
 PCI: Continuation of prior therapy
60