stable angina

ByBy

Essam Mahfouz, MDEssam Mahfouz, MDProfessor of Cardiology Mansoura University

OverviewOverview Definitions & Historical perspectivesDefinitions & Historical perspectives PathophysiologyPathophysiology Clinical presentationsClinical presentations Classifications & gradingClassifications & grading InvestigationsInvestigations Risk stratificationRisk stratification Management Management

Definition Definition Angina pectoris (literally “strangling” in the

chest) is a recurrent symptom complex of

discomfort in the chest or related areas

associated with myocardial ischemia or

dysfunctions but without myocardial necrosis,

characteristically, the discomfort is produced

by exertion and promptly relieved by rest or

nitroglcerine

“But there is a disorder of the breast marked with strong and peculiar symptoms, considerable for the kind of danger belonging to it, and not extremely rare, which deserves to be mentioned more at length. The seat of it, and the sense of strangling and anxiety with which it is attended, may make it not improperly be called angina pectoris. Those who are afflicted with it are seized while they are walking (more especially if it be uphill, and soon after eating), with a painful and most disagreeable sensation in the breast, which seems as if it would extinguish life, if it were to increase or to continue; but the moment they stand still, all this uneasiness vanishes.” William Heberden first published 225 years ago.

Angina pectoris: a glossaryAngina pectoris: a glossary Stable angina A predictable pattern regarding frequency and precipitating

factors (sustained over 3 months).

New-onset angina Recently developed angina (within the previous

1 to 3 months).

Primary angina Angina at rest with obvious precipitating cause. If

primary angina develops with exercise, the level

at which it occurs is inconsistent. A synonym for

this type of angina is “variable threshold”angina.

Secondary angina Typical exertional angina associated with specific

and usually predictable forms and levels

of physical activity.

Mixed angina Composite pattern of primary and secondary

angina.

Angina pectoris: a glossaryAngina pectoris: a glossary Emotional angina Angina with specific psychological factors that

precipitate symptoms. Nocturnal angina Angina that awakens and is sometimes

associated with dreaming or sleep apnea. Angina decubitus Angina that occurs shortly after adopting the

recumbent posture. Status anginosusFrequent, recurrent, sustained angina refractory to

usual treatment. Walk-through angina Angina with effort that disappears gradually

during activity that is sustained (although usually at reduced intensity) and after which improved exercise tolerance results.

Second-wind angina A brief rest after an initial attack results in a markedly improved threshold free from angina. A

synonym is “warm-up” angina.

Angina pectoris: a glossaryAngina pectoris: a glossary Caudal angina Angina symptoms occurring in the scalp or head

via referred pain. Angina equivalents Symptoms other than pain or discomfort that are

ischemic related and serve as angina surrogates, e.g., dyspnea, diaphoresis, fatigue, or light-headedness.

Silent angina Objective manifestations of ischemia without symptoms. Crescendo angina Synonym is “accelerated” angina. Change in the

pattern of angina such that it comes on more easily, lasts longer, or is more frequent.

Acute coronary insufficiency Sustained anginal pain, i.e., 20 to 30 minutesusually at rest, that may or may not be preceded by crescendo angina and obvious precipitating factors.

Unstable angina A collection of symptoms of angina usually incorporating crescendo angina and/or acute coronary insufficiency. By definition, unstable angina includes rest pain.

Angina pectoris: a glossaryAngina pectoris: a glossary Postinfarction angina Symptoms that follow within 24 hours to 30

days of acute myocardial infarction.

Angina with normal CA Syndrome X or microvascular angina.

Variant angina Prinzmetal’s or vasospastic angina related to

epicardial coronary spasm. Pain often at rest

that is sustained and may have circadian

variation. Exercise tolerance often is normal.

Right ventricular angina Anginal symptoms developing in

association with pulmonary hypertension

thought to be secondary to right ventricular

ischemia.

Myocardial Ischemia BalanceMyocardial Ischemia Balance

Pathogenesis of AnginaPathogenesis of Angina

Conditions Provoking or Excerpting Conditions Provoking or Excerpting IschemiaIschemia

Circadian Variation in AnginaCircadian Variation in Angina

MECHANISMS THAT DECREASE MECHANISMS THAT DECREASE CORONARY BLOOD FLOWCORONARY BLOOD FLOW

Coronary stenosis constrictionCoronary stenosis constriction

Endothelial dysfunctionEndothelial dysfunction

Coronary collateral or distal coronary Coronary collateral or distal coronary vessel vasoconstriction downstream vessel vasoconstriction downstream from coronary occlusionfrom coronary occlusion

Epicardial coronary artery spasmEpicardial coronary artery spasm

Ischemic IcebergIschemic Iceberg

Clinical Presentation:Clinical Presentation:

Typical anginal pain Anginal Equivalent:

Exertional Dyspnea Exertional Fatigue

(associated with exertion and relieved by nitroglcerine)

Risk Factors

Anginal PainAnginal Pain

ATYPICAL FEATURES OF ATYPICAL FEATURES OF ANGINA PAINANGINA PAIN

Location: Radiation to right shoulder or Location: Radiation to right shoulder or arm, jaw, tongue, teetharm, jaw, tongue, teeth

Duration: Ranges from secondsDuration: Ranges from seconds** to to hourshours**

Descriptors: SharpDescriptors: Sharp**, sticking, sticking**, stabbing, , stabbing, knifelikeknifelike**, pricking, pricking**, gas, gas**

Triggers: None, meals, body positionTriggers: None, meals, body position**

Localization: Small area of chest (< 3 Localization: Small area of chest (< 3 cm)cm)**, entire right or left side,, entire right or left side,**

leg painleg pain** Associated skin or chest wall tendernessAssociated skin or chest wall tenderness**

**Usually indicates a noncardiac cause.Usually indicates a noncardiac cause.

Clinical Examination:Clinical Examination:Pale quiet sweating patientPale quiet sweating patient

Levine signLevine sign

Pulse mild tachycardia or arrhythmiasPulse mild tachycardia or arrhythmias

BP slight elevationBP slight elevation

Abnormal apex beatAbnormal apex beat

New gallop S4 or S3New gallop S4 or S3

Apical SM (MR)Apical SM (MR)

Response to CS massageResponse to CS massage

Signs of risk factorsSigns of risk factors

Grading of Angina Grading of Angina ClassClass DescriptionDescription

II Ordinary physical activity does not cause angina, it occurs with strenuous, rapid or prolonged exertion

IIII Slight limitation of ordinary activity. Angina occurs on rapid walking or climbing stairs, emotional stress, walking uphill or after meals.

IIIIII Marked limitations of ordinary physical activity. Angina occurs on walking one to two blocks on the level and climbing one flight of stairs

IVIV Inability to carry on any physical activity without

Discomfort, anginal symptoms may be present at rest.

S-T elevation with ExerciseS-T elevation with Exercise

Severe EET ResponseSevere EET Response

Pseudo-normalization of T-wavePseudo-normalization of T-wave

Some non-specific ResponsesSome non-specific Responses

Patient with abnormal hemodynamic Patient with abnormal hemodynamic response decrease BPresponse decrease BP

Contraindications of Exercise TestContraindications of Exercise TestAbsolute:Absolute:

Acute myocardial infarction (within 2 d)

High-risk Uunstable angina Uncontrolled cardiac

arrhythmias causing symptoms or hemodynamic compromise

Symptomatic severe aortic stenosis

Uncontrolled symptomatic heart failure

Acute pulmonary embolus or pulmonary infarction

Acute myocarditis or pericarditis

Acute aortic dissection

Relative: Left main coronary stenosis Moderate stenotic valvular

heart disease Electrolyte abnormalities Severe arterial hypertension‡ Tachyarrhythmias or

bradyarrhythmias Hypertrophic cardiomyopathy

and other forms of outflow tract obstruction

Mental or physical impairment leading to inability to exercise adequately

High-degree atrioventricular block

CONDITIONS THAT CAN PRODUCE ST-SEGMENT CONDITIONS THAT CAN PRODUCE ST-SEGMENT SHIFTS DURING EXERCISE TESTINGSHIFTS DURING EXERCISE TESTING

Coronary artery diseaseCoronary artery disease Valvular heart diseaseValvular heart disease Congenital heart diseaseCongenital heart disease CardiomyopathiesCardiomyopathies Pericardial disordersPericardial disorders Left bundle branch blockLeft bundle branch block LVHLVH Pre-excitation conduction Pre-excitation conduction

variantsvariants MVPMVP Vasoregulatory Vasoregulatory

abnormalitiesabnormalities HyperventilationHyperventilation HypertensionHypertension

DrugsDrugso DigitalisDigitaliso Tricyclic antidepressant Tricyclic antidepressant

drugsdrugso Some antiarrhythmic agentsSome antiarrhythmic agents

Electrolyte abnormalitiesElectrolyte abnormalitieso HyperkalemiaHyperkalemiao HypokalemiaHypokalemiao HypomagnesemiaHypomagnesemiao HypercalcemiaHypercalcemiao HypocalcemiaHypocalcemia

AnemiaAnemia Nonfasting stateNonfasting state Postural changesPostural changes

Indications for Terminating Exercise Indications for Terminating Exercise Testing ACC Guidelines 2002Testing ACC Guidelines 2002

Absolute indications Drop in systolic BP of >10 mm Hg

from baseline BP despite an increase in workload, when accompanied by other evidence of ischemia

Moderate to severe angina Increasing nervous system

symptoms (eg, ataxia, dizziness, or near-syncope)

Signs of poor perfusion (cyanosis or pallor)

Technical difficulties in monitoring ECG or systolic BP

Subject’s desire to stop Sustained ventricular tachycardia ST elevation (> 1.0 mm) in leads

without diagnostic Q-waves (other than V1 or aVR)

Relative indications Drop in systolic BP of >10 mm Hg from

baseline BP despite an increase in workload, in the absence of other evidence of ischemia

ST or QRS changes such as excessive ST depression ( >2 mm of horizontal or downsloping ST-segment depression) or marked axis shift

Arrhythmias other than sustained ventricular tachycardia, including multifocal PVCs, triplets of PVCs, supraventricular tachycardia, heart block, or bradyarrhythmias

Fatigue, shortness of breath, wheezing, leg cramps, or claudication

Development of BBB or IVCD that cannot be distinguished from VT

Increasing chest pain Hypertensive response

High-risk Exercise Test High-risk Exercise Test

Inability to complete 6 minutes (Bruce protocol)Inability to complete 6 minutes (Bruce protocol)

Early positive test, i.e., 3 minutesEarly positive test, i.e., 3 minutes

Strongly positive test i.e., 2 minutes ST depressionStrongly positive test i.e., 2 minutes ST depression

Sustained ST depression 3 minutes after cessation Sustained ST depression 3 minutes after cessation of exerciseof exercise

Downsloping ST depressionDownsloping ST depression

Ischemia developed at a low heart rate( 120 bpm)Ischemia developed at a low heart rate( 120 bpm)

Flat or lowered blood pressure responseFlat or lowered blood pressure response

Serious ventricular arrhythmia Serious ventricular arrhythmia

Silent IschemiaSilent IschemiaAt least 75% of the ischemia occurring in At least 75% of the ischemia occurring in patients with stable angina is clinically silentpatients with stable angina is clinically silent

silent ischemia, may be categorized into silent ischemia, may be categorized into 3types:Cohn 19873types:Cohn 1987 type 1 patients are totally asymptomatictype 1 patients are totally asymptomatic type 2 are those who are symptomatic after a type 2 are those who are symptomatic after a

prior documented myocardial infarctionprior documented myocardial infarction type 3 patients manifest silent ischemia but also type 3 patients manifest silent ischemia but also

have symptomatic ischemiahave symptomatic ischemia

METHODS TO DETECT SILENT METHODS TO DETECT SILENT MYOCARDIAL ISCHEMIAMYOCARDIAL ISCHEMIA

Exercise stress testing with ECG monitoringExercise stress testing with ECG monitoring Ambulatory ECG monitoringAmbulatory ECG monitoring Exercise stress echocardiographyExercise stress echocardiography Dobutamine stress echocardiographyDobutamine stress echocardiography Stress radionuclide angiographyStress radionuclide angiography Ambulatory left ventricular function monitoring (VEST)Ambulatory left ventricular function monitoring (VEST) Positron emission tomographyPositron emission tomography Exercise stress thallium-201 scanningExercise stress thallium-201 scanning Adenosine thallium-201 scanningAdenosine thallium-201 scanning Dipyridamole thallium-201 scanningDipyridamole thallium-201 scanning

PERSONS FOR WHOM SCREENING PERSONS FOR WHOM SCREENING FOR SMI MAY BE USEFULFOR SMI MAY BE USEFUL

ASYMPTOMATIC PERSONSASYMPTOMATIC PERSONS Men older than 40 years with at least two other traditional Men older than 40 years with at least two other traditional

cardiac risk factorscardiac risk factors Postmenopausal women older than 55 years with at least two Postmenopausal women older than 55 years with at least two

other traditional cardiac risk factorsother traditional cardiac risk factors Those at high risk for premature atherosclerosis (Those at high risk for premature atherosclerosis (eg,eg, familial familial

heperlipidemia, evidence of severe hypercholesterolemia, heperlipidemia, evidence of severe hypercholesterolemia, family history of coronary artery disease at an early age)family history of coronary artery disease at an early age)

Those with ECG evidence of prior unrecognized myocardial Those with ECG evidence of prior unrecognized myocardial infarctioninfarction

Those > 5 years after coronary artery bypassThose > 5 years after coronary artery bypass

PERSONS FOR WHOM SCREENING PERSONS FOR WHOM SCREENING FOR SMI MAY BE USEFULFOR SMI MAY BE USEFUL

SYMPTOMATIC PERSONSSYMPTOMATIC PERSONS

Those with stable angina well controlled by medicationThose with stable angina well controlled by medication

Those with unstable angina after rest and pain well controlled Those with unstable angina after rest and pain well controlled

by medicationby medication

Those who have experienced myocardial infarctionThose who have experienced myocardial infarction

Those who have survived nearly fatal cardiac eventsThose who have survived nearly fatal cardiac events

Those with peripheral vascular disease or cerebrovascular Those with peripheral vascular disease or cerebrovascular

disease to undergo noncardiac surgerydisease to undergo noncardiac surgery

High-Risk (greater than 3% annual mortality rate)

Severe resting left ventricular dysfunction (LVEF < 35%)

High-risk treadmill score (score < –11) Severe exercise left ventricular dysfunction (exercise

LVEF < 35%) Stress-induced large perfusion defect (particularly

if anterior) Stress-induced multiple perfusion defects of moderate size

Risk StratificationRisk Stratification ACC Guidelines 2002ACC Guidelines 2002


Intermediate-Risk (1%-3% annual mortality rate)

1) Mild/moderate resting left ventricular dysfunction (LVEF = 35% to 49%)

2) Intermediate-risk treadmill score (–11 < score < 5)3) Stress-induced moderate perfusion defect without

LV dilation or increased lung intake (thallium-201)

4) Limited stress echocardiographic ischemia with a wall motion abnormality only at higher doses of dobutamine involving less than or equal to two segments

6. Large, fixed perfusion defect with LV dilation or increased

lung uptake (thallium-201)

7. Stress-induced moderate perfusion defect with LV dilation

or increased lung uptake (thallium-201)

8. Echocardiographic wall motion abnormality (involving

greater than two segments) developing at low dose of

dobutamine (>10 mg/kg/min) or at a low heart rate (<120

beats/min)

9. Stress echocardiographic evidence of extensive ischemia



Low-Risk (less than 1% annual mortality rate)

1. Low-risk treadmill score (score >5)

2. Normal or small myocardial perfusion defect at rest or with stress*

3. Normal stress echocardiographic wall motion or no change of limited resting wall motion abnormalities during stress*

FACTORS INFLUENCING FACTORS INFLUENCING CLINICAL OUTCOME IN ANGINACLINICAL OUTCOME IN ANGINA

Number of coronary arteries diseased, (eg, one-, two-, or three-vessel disease)

Presence or absence of left main coronary artery disease

Extent of ischemia or amount of jeopardized myocardium

Status of left ventricular function

ACC Guidelines 2002 for Stable ACC Guidelines 2002 for Stable Angina Angina

A = Aspirin and Antianginal therapy

B = Beta-blocker and Blood pressure

C = Cigarette smoking and Cholesterol

D = Diet and Diabetes

E = Education and Exercise

CANDIDATES FOR USE OF CANDIDATES FOR USE OF NITRATES FOR ANGINANITRATES FOR ANGINAIDEAL CANDIDATESIDEAL CANDIDATES

Consistent response to sublingual nitroglycerinConsistent response to sublingual nitroglycerin Patients suspected of having episodes of vasoconstriction (mixed Patients suspected of having episodes of vasoconstriction (mixed

angina), eg, variable effort threshold, rest, or mental stress anginaangina), eg, variable effort threshold, rest, or mental stress angina Left ventricular dysfunction: congestive heart failure, reduced ejection Left ventricular dysfunction: congestive heart failure, reduced ejection

fraction, cardiomegalyfraction, cardiomegaly Postinfarction anginaPostinfarction angina

POOR CANDIDATESPOOR CANDIDATES Persistent or intolerable headache, nausea, or dizzinessPersistent or intolerable headache, nausea, or dizziness Nitrate hypersensitivityNitrate hypersensitivity Limited clinical response to long-acting nitratesLimited clinical response to long-acting nitrates

CANDIDATES FOR USE OFCANDIDATES FOR USE OFB-BLOCKERS FOR ANGINAB-BLOCKERS FOR ANGINA

IDEAL CANDIDATESIDEAL CANDIDATES Prominent relationship of physical activity to attacks of anginaProminent relationship of physical activity to attacks of angina Coexistent hypertensionCoexistent hypertension History of supraventricular or ventricular arrhythmiaHistory of supraventricular or ventricular arrhythmia Postmyocardial infarction anginaPostmyocardial infarction angina Prominent anxiety stateProminent anxiety state

POOR CANDIDATESPOOR CANDIDATES Asthma or reversible airway component in chronic lung patientsAsthma or reversible airway component in chronic lung patients DiabetesDiabetes Severe left ventricular dysfunctionSevere left ventricular dysfunction Congestive heart failure resulting from systolic impairmentCongestive heart failure resulting from systolic impairment History of depressionHistory of depression Raynaud’s phenomenonRaynaud’s phenomenon Peripheral vascular diseasePeripheral vascular disease BradyarrhythmiaBradyarrhythmia

CANDIDATES FOR USE OF CALCIUM CANDIDATES FOR USE OF CALCIUM ANTAGONISTS FOR ANGINAANTAGONISTS FOR ANGINA

IDEAL CANDIDATESIDEAL CANDIDATES With coexistent hypertension Believed to have episodes of vasoconstriction (mixed

angina) or vasospasm With supraventricular arrhythmia (verapamil or diltiazem

POOR CANDIDATESPOOR CANDIDATES Severe left ventricular dysfunction or congestive heart

failure Bradyarrhythmias (sinus bradycardia, slow atrial

fibrillation, atrioventricular node block); such individuals should not be given verapamil or diltiazem

Anti-Anginal Therapies Anti-Anginal Therapies Indications Indications Contraindications Contraindications

B-BlockersB-Blockers Post-MI Post-MI

CHF (compensated) CHF (compensated)

Ventricular tachycardia Ventricular tachycardia

SVT SVT

Systemic hypertension Systemic hypertension

HyperthyroidismHyperthyroidism

Decompensated HF Decompensated HF

Severe bradycardia or AV Severe bradycardia or AV block block

Severe depression Severe depression

Symptomatic PAD Symptomatic PAD

Raynaud's phenomenon Raynaud's phenomenon

Severe COPDSevere COPD

DHP-CCBDHP-CCB Systemic hypertension Systemic hypertension

Raynaud's phenomenon or Raynaud's phenomenon or Prinzmetal's angina Prinzmetal's angina

Severe bradycardia or AV blockSevere bradycardia or AV block

HypotensionHypotension

Non DHP-Non DHP-CCBCCB

SVT SVT

Systemic hypertensionSystemic hypertension

Severe bradycardia Severe bradycardia

Significant AV block Significant AV block

LV dysfunction or HFLV dysfunction or HF

Anti-Anginal Therapies Anti-Anginal Therapies Indications Indications Contraindications Contraindications

NitratesNitrates LV dysfunction or HFLV dysfunction or HF Severe aortic stenosis Severe aortic stenosis

PDE5 inhibitor usePDE5 inhibitor use

Ivaprdine Ivaprdine Increased resting heart Increased resting heart

raterate Bradycardia Bradycardia

2° AV block2° AV block

Ranolazine Ranolazine Bradycardia or AV block Bradycardia or AV block

Low blood pressure Low blood pressure

LV dysfunction LV dysfunction

Possible diabetesPossible diabetes

Treatment with QT-Treatment with QT-prolonging agents prolonging agents

Moderate or severe Moderate or severe

hepatic dysfunctionhepatic dysfunction

Nicorandil Nicorandil Refractory anginaRefractory angina Similar to nitrate Similar to nitrate

EVALUATION OF CORONARY REVASCULARIZATION FOR EVALUATION OF CORONARY REVASCULARIZATION FOR

PROLONGING SURVIVALPROLONGING SURVIVAL

1. Age

2. Severity of symptoms

3. Stress testing and severity of ischemia

4. Ventricular function

5. Coronary anatomy

6. Extent and site of disease

7. Potential for revascularization

8. Coexisting medical conditions

FACTORS IN SELECTING MYOCARDIAL FACTORS IN SELECTING MYOCARDIAL REVASCULARIZATION OVER MEDICAL REVASCULARIZATION OVER MEDICAL THERAPY IN PATIENTS WITH ANGINATHERAPY IN PATIENTS WITH ANGINACLINICALCLINICAL

Poor or partial response to intensive medical therapyPoor or partial response to intensive medical therapy Lifestyle (occupation, recreation) limited stable angina on medical Lifestyle (occupation, recreation) limited stable angina on medical

therapytherapy

NONINVASIVENONINVASIVE Objective evidence for major ischemiaObjective evidence for major ischemia Strongly positive stress test (low workload, ST-segment depression ³ 2 Strongly positive stress test (low workload, ST-segment depression ³ 2

mm, failure of systolic blood pressure to rise, early onset of ischemia)mm, failure of systolic blood pressure to rise, early onset of ischemia) Large, reversible thallium defect; two or more reversible thallium Large, reversible thallium defect; two or more reversible thallium

defects; increased lung thallium uptakedefects; increased lung thallium uptake Extensive or multiple wall motion abnormalities on stress Extensive or multiple wall motion abnormalities on stress

echocardiography or stress radionuclide angiographyechocardiography or stress radionuclide angiography Strongly positive ambulatory recording: > four episodes of ST Strongly positive ambulatory recording: > four episodes of ST

depression per day, >30 min of ST depression per daydepression per day, >30 min of ST depression per day

FACTORS IN SELECTING MYOCARDIAL FACTORS IN SELECTING MYOCARDIAL REVASCULARIZATION OVER MEDICAL REVASCULARIZATION OVER MEDICAL THERAPY IN PATIENTS WITH ANGINATHERAPY IN PATIENTS WITH ANGINAINVASIVEINVASIVE

Main left coronary artery stenosis or three-vessel disease, Main left coronary artery stenosis or three-vessel disease, especially if LV function is decreased (CABG)especially if LV function is decreased (CABG)

Two-vessel disease with decreased LV function and/or Two-vessel disease with decreased LV function and/or proximal LAD involvementproximal LAD involvement

Two-vessel disease with frequent symptoms or ischemia on Two-vessel disease with frequent symptoms or ischemia on noninvasive testing while on medical therapynoninvasive testing while on medical therapy

One-vessel disease with easily induced ischemia on medical One-vessel disease with easily induced ischemia on medical therapy (PTCA)therapy (PTCA)

PTCA Vs Medical TherapyPTCA Vs Medical Therapy

COURAGE

COURAGE

Clinical Outcomes Utilizing

Revascularization and

Aggressive Guideline-Driven

Drug Evaluation

Stable CAD: PCI vs ConservativeMedical Management

Meta-analysis of 11 randomized trials; N = 2,950

Death

Cardiac death or MI

Nonfatal MI

CABG

PCI

Katritsis DG et al. Circulation. 2005;111:2906-12.

0 1 2

P

0.68

0.28

0.12

0.82

0.34

Risk ratio(95% Cl)

Favors PCI

Favors Medical Management

PCI + Optimal Medical Therapy

will be Superior to

Optimal Medical Therapy Alone

Hypothesis

Primary Outcome

Death or Nonfatal MI

Death, MI, or Stroke

Hospitalization for Biomarker (-)

ACS

Cost, Resource Utilization

Quality of Life, including Angina

Cost-Effectiveness

Secondary Outcomes

Optimal Medical Therapy

Pharmacologic

• Anti-platelet: aspirin; clopidogrel in accordance

with established practice standards

• Statin: simvastatin ± ezetimibe or ER niacin

• ACE Inhibitor or ARB: lisinopril or losartan

• Beta-blocker: long-acting metoprolol

• Calcium channel blocker: amlodipine

• Nitrate: isosorbide 5-mononitrate

Applied to Both Arms by Protocol and Case-Managed

Survival Free of Death from Any Cause and Myocardial Infarction

Number at Risk

Medical Therapy 1138 1017 959 834 638 408 192 30PCI 1149 1013 952 833 637 417 200 35

Years0 1 2 3 4 5 6

0.0

0.5

0.6

0.7

0.8

0.9

1.0

PCI + OMT

Optimal Medical Therapy (OMT)

Hazard ratio: 1.0595% CI (0.87-1.27)P = 0.62

7

Overall Survival

Number at Risk


Years0 1 2 3 4 5 6

0.0

0.5

0.6

0.7

0.8

0.9

1.0

PCI + OMT

OMT

7

Hazard ratio: 0.8795% CI (0.65-1.16)P = 0.38

Survival Free of Hospitalization for ACS

Number at Risk


Years0 1 2 3 4 5 6

0.0

0.5

0.6

0.7

0.8

0.9

1.0

PCI + OMT

OMT

7

Hazard ratio: 1.0795% CI (0.84-1.37)P = 0.56

Survival Free ofMyocardial Infarction

Number at Risk


Years0 1 2 3 4 5 6

0.0

0.5

0.6

0.7

0.8

0.9

1.0

PCI + OMT

OMT

7

Hazard ratio: 1.1395% CI (0.89-1.43)P = 0.33

Subgroup Analyses

1.00

PCI Better Medical Therapy Better

Baseline Characteristics

Hazard Ratio (95% Cl) PCI

Medical Therapy

0.500.25 1.50

Overall 1.05 (0.87-1.27) 0.19 0.19Sex Male 1.15 (0.93-1.42) 0.19 0.18 Female 0.65 (0.40-1.06) 0.18 0.26Age > 65 1.10 (0.83-1.46) 0.24 0.22 ≤ 65 1.00 (0.77-1.32) 0.16 0.16Race White 1.08 (0.87-1.34) 0.19 0.18 Not White 0.87 (0.54-1.42) 0.19 0.24Health Care System Canadian 1.27 (0.90-1.78) 0.17 0.14 U.S. Non-VA 0.71 (0.44-1.14) 0.15 0.21 U.S. VA 1.06 (0.80-1.38) 0.22 0.22

1.75 2.00

Myocardial Infarction Yes 1.15 (0.93-1.42) 0.19 0.18 No 0.65 (0.40-1.06) 0.18 0.26Extent of CAD Multi-vessel disease 1.10 (0.83-1.46) 0.24 0.22 Single-vessel disease 1.00 (0.77-1.32) 0.16 0.16Diabetes Yes 1.08 (0.87-1.34) 0.19 0.18 No 0.87 (0.54-1.42) 0.19 0.24Angina CCS 0-I 1.27 (0.90-1.78) 0.17 0.14 CCS II-III 0.71 (0.44-1.14) 0.15 0.21Ejection Fraction ≤ 50% 1.06 (0.80-1.38) 0.22 0.22 > 50% 1.06 (0.80-1.38) 0.22 0.22Previous CABG No 1.06 (0.80-1.38) 0.22 0.22 Yes 1.06 (0.80-1.38) 0.22 0.22

Subgroup Analyses

1.00

PCI Better Medical Therapy Better

Baseline Characteristics Hazard Ratio (95% Cl) PCI

Medical Therapy

0.500.25 1.50 1.75 2.00

Conclusions Conclusions • As an initial management strategy in patients

with stable coronary artery disease, PCI did not reduce the risk of death, MI, or other major cardiovascular events when added to optimal medical therapy

• As expected, PCI resulted in better angina relief during most of the follow-up period, but medical therapy was also remarkably effective, with no between–group difference in angina-free status at 5 years

ImplicationsImplications• Our findings reinforce existing ACC/AHA clinical

practice guidelines, which state that PCI can be safely deferred in patients with stable CAD, even in those with extensive, multivessel involvement and inducible ischemia, provided that intensive, multifaceted medical therapy is instituted and maintained

• Optimal medical therapy and aggressive management of multiple treatment targets without initial PCI can be implemented safely in the majority of patients with stable CAD—two-thirds of whom may not require even a first revascularization during long-term follow-up

stable angina

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