Stable angina

ByBy
Essam Mahfouz, MDEssam Mahfouz, MD
Professor of Cardiology Mansoura University

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

DefinitionDefinition
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.

 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 anginosus Frequent, 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.

 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.

 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 ExcerptingConditions Provoking or Excerpting
IschemiaIschemia

Circadian Variation in AnginaCircadian Variation in Angina

MECHANISMS THAT DECREASEMECHANISMS THAT DECREASE
CORONARY BLOOD FLOWCORONARY BLOOD FLOW
Coronary stenosis constrictionCoronary stenosis constriction
Endothelial dysfunctionEndothelial dysfunction
Coronary collateral or distal coronaryCoronary collateral or distal coronary
vessel vasoconstriction downstreamvessel 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 OFATYPICAL FEATURES OF
ANGINA PAINANGINA PAIN
 Location: Radiation to right shoulder orLocation: Radiation to right shoulder or
arm, jaw, tongue, teetharm, jaw, tongue, teeth
 Duration: Ranges from secondsDuration: Ranges from seconds** toto
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 (< 3Localization: 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 AnginaGrading 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 hemodynamicPatient with abnormal hemodynamic
response decrease BPresponse decrease BP

Contraindications of Exercise TestContraindications of Exercise Test
Absolute: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-SEGMENTCONDITIONS 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 conductionPre-excitation conduction
variantsvariants
 MVPMVP
 VasoregulatoryVasoregulatory
abnormalitiesabnormalities
 HyperventilationHyperventilation
 HypertensionHypertension
 DrugsDrugs
o DigitalisDigitalis
o Tricyclic antidepressantTricyclic antidepressant
drugsdrugs
o Some antiarrhythmic agentsSome antiarrhythmic agents
 Electrolyte abnormalitiesElectrolyte abnormalities
o HyperkalemiaHyperkalemia
o HypokalemiaHypokalemia
o HypomagnesemiaHypomagnesemia
o HypercalcemiaHypercalcemia
o HypocalcemiaHypocalcemia
 AnemiaAnemia
 Nonfasting stateNonfasting state
 Postural changesPostural changes

Indications for Terminating ExerciseIndications 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 TestHigh-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 cessationSustained 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 arrhythmiaSerious ventricular arrhythmia

Silent IschemiaSilent Ischemia
At least 75% of the ischemia occurring inAt least 75% of the ischemia occurring in
patients with stable angina is clinicallypatients with stable angina is clinically
silentsilent
silent ischemia, may be categorized intosilent 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 atype 2 are those who are symptomatic after a
prior documented myocardial infarctionprior documented myocardial infarction
 type 3 patients manifest silent ischemia but alsotype 3 patients manifest silent ischemia but also
have symptomatic ischemiahave symptomatic ischemia

METHODS TO DETECT SILENTMETHODS 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 SCREENINGPERSONS 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 traditionalMen older than 40 years with at least two other traditional
cardiac risk factorscardiac risk factors
 Postmenopausal women older than 55 years with at least twoPostmenopausal 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, familialfamilial
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 myocardialThose with ECG evidence of prior unrecognized myocardial
infarctioninfarction
 Those > 5 years after coronary artery bypassThose > 5 years after coronary artery bypass

PERSONS FOR WHOM SCREENINGPERSONS 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 controlledThose 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 cerebrovascularThose 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 INFLUENCINGFACTORS 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 StableACC Guidelines 2002 for Stable
AnginaAngina
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 OFCANDIDATES FOR USE OF
NITRATES FOR ANGINANITRATES FOR ANGINA
IDEAL CANDIDATESIDEAL CANDIDATES
 Consistent response to sublingual nitroglycerinConsistent response to sublingual nitroglycerin
 Patients suspected of having episodes of vasoconstriction (mixedPatients 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 ejectionLeft 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 OF
B-BLOCKERS FOR ANGINAB-BLOCKERS FOR ANGINA
 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
 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 CALCIUMCANDIDATES FOR USE OF CALCIUM
ANTAGONISTS FOR ANGINAANTAGONISTS FOR ANGINA
 With coexistent hypertension
 Believed to have episodes of vasoconstriction (mixed
angina) or vasospasm
 With supraventricular arrhythmia (verapamil or diltiazem
 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 TherapiesAnti-Anginal Therapies
IndicationsIndications ContraindicationsContraindications
B-BlockersB-Blockers Post-MIPost-MI
CHF (compensated)CHF (compensated)
Ventricular tachycardiaVentricular tachycardia
SVTSVT
Systemic hypertensionSystemic hypertension
HyperthyroidismHyperthyroidism
Decompensated HFDecompensated HF
Severe bradycardia or AVSevere bradycardia or AV
blockblock
Severe depressionSevere depression
Symptomatic PADSymptomatic PAD
Raynaud's phenomenonRaynaud's phenomenon
Severe COPDSevere COPD
DHP-CCBDHP-CCB Systemic hypertensionSystemic hypertension
Raynaud's phenomenon orRaynaud's phenomenon or
Prinzmetal's anginaPrinzmetal's angina
Severe bradycardia or AV blockSevere bradycardia or AV block
HypotensionHypotension
Non DHP-Non DHP-
CCBCCB
SVTSVT
Systemic hypertensionSystemic hypertension
Severe bradycardiaSevere bradycardia
Significant AV blockSignificant AV block
LV dysfunction or HFLV dysfunction or HF

Anti-Anginal TherapiesAnti-Anginal Therapies
IndicationsIndications ContraindicationsContraindications
NitratesNitrates LV dysfunction or HFLV dysfunction or HF Severe aortic stenosisSevere aortic stenosis
PDE5 inhibitor usePDE5 inhibitor use
IvaprdineIvaprdine Increased resting heartIncreased resting heart
raterate
BradycardiaBradycardia
2° AV block2° AV block
RanolazineRanolazine Bradycardia or AV blockBradycardia or AV block
Low blood pressureLow blood pressure
LV dysfunctionLV dysfunction
Possible diabetesPossible diabetes
Treatment with QT-Treatment with QT-
prolonging agentsprolonging agents
Moderate or severeModerate or severe
hepatic dysfunctionhepatic dysfunction
NicorandilNicorandil Refractory anginaRefractory angina Similar to nitrateSimilar to nitrate

EVALUATION OF CORONARY REVASCULARIZATION FOREVALUATION 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 MYOCARDIALFACTORS IN SELECTING MYOCARDIAL
REVASCULARIZATION OVER MEDICALREVASCULARIZATION OVER MEDICAL
THERAPY IN PATIENTS WITH ANGINATHERAPY IN PATIENTS WITH ANGINA
CLINICALCLINICAL
 Poor or partial response to intensive medical therapyPoor or partial response to intensive medical therapy
 Lifestyle (occupation, recreation) limited stable angina on medicalLifestyle (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 2Strongly 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 thalliumLarge, reversible thallium defect; two or more reversible thallium
defects; increased lung thallium uptakedefects; increased lung thallium uptake
 Extensive or multiple wall motion abnormalities on stressExtensive or multiple wall motion abnormalities on stress
echocardiography or stress radionuclide angiographyechocardiography or stress radionuclide angiography
 Strongly positive ambulatory recording: > four episodes of STStrongly 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 MYOCARDIALFACTORS IN SELECTING MYOCARDIAL
REVASCULARIZATION OVER MEDICALREVASCULARIZATION OVER MEDICAL
THERAPY IN PATIENTS WITH ANGINATHERAPY IN PATIENTS WITH ANGINA
INVASIVEINVASIVE
 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/orTwo-vessel disease with decreased LV function and/or
proximal LAD involvementproximal LAD involvement
 Two-vessel disease with frequent symptoms or ischemia onTwo-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 medicalOne-vessel disease with easily induced ischemia on medical
therapy (PTCA)therapy (PTCA)

PTCA Vs Medical TherapyPTCA Vs Medical Therapy

COURAGE
Clinical Outcomes Utilizing
Revascularization and
Aggressive Guideline-Driven
Drug Evaluation

Stable CAD: PCI vs Conservative
Medical 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 30
PCI 1149 1013 952 833 637 417 200 35
Years
0 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: 1.05
95% CI (0.87-1.27)
P = 0.62
7

Overall Survival
Number at Risk
Medical Therapy 1138 1073 1029 917 717 468 302 38
PCI 1149 1094 1051 929 733 488 312 44
Years
0 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: 0.87
95% CI (0.65-1.16)
P = 0.38

Survival Free of Hospitalization
for ACS
Number at Risk
Medical Therapy 1138 1025 956 833 662 418 236 127
PCI 1149 1027 957 835 667 431 246 134
Years
0 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: 1.07
95% CI (0.84-1.37)
P = 0.56

Survival Free of
Myocardial Infarction
Number at Risk
Medical Therapy 1138 1019 962 834 638 409 192 120
PCI 1149 1015 954 833 637 418 200 134
Years
0 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: 1.13
95% 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
0.19
Sex
Male 1.15 (0.93-1.42) 0.19 0.18
Female 0.65 (0.40-1.06) 0.18 0.26
Age
> 65 1.10 (0.83-1.46) 0.24
0.22
≤ 65 1.00 (0.77-1.32) 0.16
0.16
Race
White 1.08 (0.87-1.34) 0.19
0.18
Not White 0.87 (0.54-1.42) 0.19 0.24
Health 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
0.26
Extent 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 0.16
Diabetes
Yes 1.08 (0.87-1.34) 0.19
0.18
No 0.87 (0.54-1.42) 0.19
0.24
Angina
CCS 0-I 1.27 (0.90-1.78) 0.17 0.14
CCS II-III 0.71 (0.44-1.14) 0.15 0.21
Ejection Fraction
≤ 50% 1.06 (0.80-1.38) 0.22
0.22
> 50% 1.06 (0.80-1.38) 0.22
0.22
Previous 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

ConclusionsConclusions
• 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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