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Chronic Stable Angina:
Evidence-Based Guide to
Revascularization
Khôi M. Lê, MD
Desert Cardiology Center
Eisenhower Medical Center
Rancho Mirage, California
USA
Why do we treat?
 To help the person live longer (reducing mortality)
 To help the person live better (reducing symptoms)
Standard treatment options for
angina
Lifestyle modifications Medications
Angioplasty/stenting Bypass surgery
Outline
 Review selected landmark clinical trials
 FAME
 COURAGE
 BARI 2D
 MASS II
 SYNTAX
 Provide a framework for decision-making
 Guidelines
 Appropriateness criteria
FAME
Tonino PA et al. N Engl J Med 2009;360:213-224.
Fractional flow reserve (FFR)
measurements vs angiography
to guide PCI decision-making
Findings from FAME

Tonino PA et al. N Engl J Med 2009;360:213-224.
Fractional flow reserve
measurements are
superior to angiography
in guiding decision-
making regarding
revascularization
Treatment of
nonischemic lesions led
to worse clinical
outcomes
Kaplan-Meier Survival Curves
Boden WE et al. N Engl J Med 2007;356:1503-1516
COURAGE: No difference in
long-term survival, ACS, MI
COURAGE: Angina-free (%)
P= NS
P<0.001 P=0.02
P=NS
Angina relief is higher
in the PCI group at 1
and 2 years, but there is
also substantial
improvement with
medical-therapy
At 5 years angina relief
is equivalent
Weintraub WS et al. N Engl J Med 2008;359:677-687
COURAGE:
Effect of PCI on

Quality of Life in
Patients with Stable
Coronary Disease
* Indicates P<0.01 for
difference between treatment
groups
COURAGE: Need for
Subsequent Revascularization
 At a median 4.6 year follow-up, 21.1% of the PCI patients required an
additional revascularization, compared to 32.6% of the OMT group
who required a 1
st
revascularization
 77 patients in the PCI group and 81 patients in the OMT group
required subsequent CABG surgery
 Median time to subsequent revascularization was 10.0 mo in the PCI
group and 10.8 mo in the OMT group
Mortality in Randomized Trials Comparing
the PCI With Medical Treatment
 Meta-analysis of 7513
patients in 17
randomized trials
 PCI was associated
with a 20% reduction in
death
 COURAGE may have
been underpowered to
detect a mortality
benefit
20%

reduction
JACC 2008;52:894-904
Lifestyle Pharmacologic
COURAGE:
Optimal Medical Therapy
 Smoking cessation
 Exercise program
 Nutrition counseling
 Weight control
 Anti-platelet
 Statin ± ezetimibe or ER
niacin
 Beta-blocker
 Calcium channel blocker
 Long-acting nitrate
 ACE Inhibitor or ARB
COURAGE: Risk factor goals
Variable Goal
Smoking Cessation
Total Dietary Fat / Saturated Fat <30% calories / <7% calories
Dietary Cholesterol <200 mg/day
LDL cholesterol (primary goal) 60-85 mg/dL
HDL cholesterol (secondary goal) >40 mg/dL
Triglyceride (secondary goal) <150 mg/dL
Physical Activity 30-45 min. moderate intensity 5X/week
Body Weight by Body Mass index Initial BMI
Weight Loss Goal
25-27.5 BMI <25
>27.5 10% relative weight loss
Blood Pressure <130/85 mmHg

Diabetes HbAlc <7.0%
COURAGE:
Optimal medical
therapy
Percent of Patients Taking
Medications During the
Trial
Maron, D. J. et al. J Am Coll
Cardiol 2010;55:1348-1358
The COURAGE trial:
Take home messages
 For every 1000 patients treated with a PCI-first strategy,
compared to optimal medical therapy
≈ 800+ will have the same outcome as those treated medically
+ 60-90 will have symptomatic benefit for 6-24 months
− 28 will have a periprocedural myocardial infarction
− 2 will die
 Consider treating patients with stable symptoms with medical
therapy first and reserving PCI for continued symptoms
Additional insights from
COURAGE
 Identification of patients that will likely respond inadequately
to optimal medical therapy
 Identification of patients at high-risk for future clinical events:
Can revascularization be protective?
COURAGE:
Benefit of PCI is related to
baseline frequency of angina
Multiple episodes per week
About 1 episode per week

Episodes only rarely
Years from Baseline
Seattle Angina Scores (higher scores = less angina)
Weintraub WS et al. N Engl J Med 2008;359:677-687
COURAGE: Baseline and
posttreatment gated MPS results
P=0.63 P<0.0001
P=0.06
P=0.02
P=0.0004
Shaw L J et al. Circulation 2008;117:1283-1291
Shaw L J et al. Circulation 2008;117:1283-1291
Kaplan–Meier survival for
patients by residual ischemia,
after 6 to 18 months of
PCI+OMT or OMT.
Extent of residual ischemia is predictive of cardiac
events (death/MI)
COURAGE
Modification of message?
Although patients with ischemic heart disease and stable
symptoms should be offered optimal medical therapy initially,
those with severe symptoms and/or a significant burden of
ischemia may benefit from early rather than deferred
revascularization
BARI 2D: Trial design and enrollment
The BARI 2D Study Group. N Engl J Med 2009;360:2503-
2515
BARI 2D: Rates of Survival and Freedom from Major
Cardiovascular Events, According to PCI and CABG Strata

NEJM 2009;360:2503-2515
• There was no survival
benefit to early
revascularization over
medical therapy
• The subset of patients
with a greater extent of
CAD (selected for the
CABG vs medical
therapy stratum) may
benefit from earlier
revascularization
• Overall, the findings
confirm the results of
the COURAGE trial
Patient Selection Treatment and Follow-up
MASS II: Study Design
 Multivessel proximal
coronary stenoses >70%
 Ischemia
 Stress testing
 CCS class II or III
 Appropriate for PCI or
CABG
 Randomized
 Optimal medical therapy
 PCI
 CABG
 Primary endpoint composite
of death, MI, angina

requiring revascularization
 Follow-up every 6 months
for 10 years
MASS II: Major Adverse Cardiac
Events at 10-year Follow-up
Hueb W et al. Circulation 2010;122:949-957
Conclusions from MASS II
 In patients with stable angina and multivessel disease,
revascularization, especially bypass surgery, reduces cardiac
death and MI.
 COURAGE and MASS II results, although apparently
contradictory, can be reconciled by considering the extent of
disease
 Single vessel disease (31% in COURAGE, 0% in MASS II)
 Proximal LAD disease (34% in COURAGE, 92% in MASS II)
 CCS Class 0 or I (42% in COURAGE, 0% in MASS II)