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:

pricking, gas Sharp, sticking, stabbing, knifelike, 

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

Nitrates Eccentric

5

Concentric

Risk Factors for Coronary Artey Disease

Modifiable CAD Risk Factors Causative Risk Factors (directly associated with CAD development)

o o o o o Cigarette smoking Hypertension Kidney disease Diabetes mellitus (Type-1 & 2) Elevated LDL & Reduced HDL

Predisposing Risk factors (Direct Impact on Causative RF Development) Non-modifiable CAD Risk Factors

Obesity (BMI? 25 kg/m Physical inactivity Socioeconomic factors 2 )

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

Smoking Blood Pressure Lipid Metabolism Diabetes Physical activity Body Weight Influenza vaccination

Intervention & Goal

Complete cessation <140/90 mm Hg & <130/80 mm Hg in diabetics & kidney disease LDL-C <100 mg/dL, If triglycerides >200 mg/dL, non –HDL-C should be <130 mg/dL Hemoglobin A 1C <7% At least 30 min of moderate intensity aerobic activity (e.g., brisk walking) for minimum of 5 days/wk BMI between 18.5

–24.9 kg/m 2 Waist circumference men <40 in, women <35 in 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 o

Nitrates 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 →

S nitrothiols

→

Activation of

Guanylate cyclase

→ Increased intracellular cGMP 

Venous dilation

→

lowered preload

→reduction of ventricular filling pressure → decreased myocardial 12 O 2 consumption → anginal pain relief

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 perio d 13

Short-Acting Nitrates Sublingual Nitroglycerin (NTG)

 Dose: mostly 0.4 mg, relief of pain, objective hemodynamic 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: o Sit immediately, place NTG tablet under tongue o o o o 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 An open bottle →use for 6-12 months 14

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):

release tablets SR tab, rapid 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 o Severe hypotension & bradycardia caused cardiac arrest in patients experiencing MI NTG-induced vaso vagal response → NTG syncope → leg elevation, atropine, fluids 

Met-Hbemia

doses used is important when large IV NTG 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

tolerance to therapeutic activity minimize  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 (O 2 ) + 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 &

allow 12 hr nitrate-free period

5 PM

to  ISDN can be given

twice/day

severity angina in moderate 

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

ß 2 adrenergic receptors contractility & HR were shown to be present in the heart by 10-40%, possibly augment cardiac  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

ß-blockers’ dose is best monitored to adjust  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 t 1/2 is 10 hours but clinical evidence support the effectiveness of once daily regimen 

Propranolol

is of short 2-3 hrs t 1/2 , 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 ß 2 induced 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 two weeks 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 O 2 demand CCBs cause

coronary dilation Coronary

→ increase myocardial O 2 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 O 2 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

28  Constipation with verapamil

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 A 2 production, whereas doses below 100 mg result in a dose-dependent reduction in thromboxane A 2 synthesis  Determine the effect of aspirin doses on the TXA 2 to PGI 2  Selective inhibition of platelet-generated TXA 2 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 had a lower incidence of death, MI, and stroke in 42 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

variant angina is the cardinal mark for  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 & 45 5-HT receptors

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 ß 2 -blockade Cardioselective ß-blockers can worsen variant 46 angina

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, NTG)

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 54 24 hrs

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

needed to prevent such reactions strategies are  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 Tirofiban

Percutaneous transluminal coronary angioplasty (PCTA) Coronary stent placement Acute coronary syndrome (unstable angina and non –STEMI) 0.25 mg/kg IV bolus, then 0.125 mcg/kg/min IV infusion × 12 hr 180 mcg/kg IV bolus, then 2.0 mcg/kg/min IV × 20–24 hr Repeat 180 mcg/kg IV bolus 10 mins after first bolus Not approved use 0.25 mg/kg IV bolus, then 0.125 mcg/kg/min IV infusion × 12 hr Same as above Not approved use 180 mcg/kg IV bolus, then 2.0 mcg/kg/min IV

× 20–24 hr

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

options for administration at the time of the are 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