stable angina
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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
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
Risk StratificationRisk Stratification ACC Guidelines 2002ACC Guidelines 2002
Risk StratificationRisk Stratification ACC Guidelines 2002ACC Guidelines 2002
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
Medical Therapy 1138 1073 1029 917 717 468 302 38PCI 1149 1094 1051 929 733 488 312 44
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
Medical Therapy 1138 1025 956 833 662 418 236 127PCI 1149 1027 957 835 667 431 246 134
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
Medical Therapy 1138 1019 962 834 638 409 192 120PCI 1149 1015 954 833 637 418 200 134
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
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