Teaching <10 minutes

1. COURAGE
OVMC LANDMARK TRIALS SERIES
Boden WE, et al. "Optimal medical therapy with or
without PCI for stable coronary disease". The New
England Journal of Medicine. 2007. 356:1503-16.

2. Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation
(COURAGE)
Summarized by Isabella Lai, MD; Laxmi Suthar, MD

3. BACKGROUND
 PCI has become prominent strategy in
management of stable CAD despite no proven
mortality benefits
 PCI has been shown to reduced rate of death,
MI, hospitalization from acute coronary
syndrome (ACS)
 However, prior to the COURAGE trial, it
remained unclear whether PCI would have an
added benefit to optimal medical therapy
 Optimal medical therapy is defined as
pharmacologic therapy and lifestyle
intervention

4. CLINICAL QUESTION
 In patients with stable CAD, how does
optimal medical therapy PLUS PCI
compare to optimal medical therapy
ALONE in reducing risk of death and
non-fatal MI?

5. DESIGN
 Analysis: Intention-to-treat
 Trial Design: Prospective, multicenter, open-label, parallel-group, randomized, controlled trial
 N=2,287 (85% power to detect an absolute difference of 4.6% in primary outcomes)
 PCI plus OMT (n=1,149)
 OMT alone (n=1,138)
 Setting: 50 centers in US and Canada
 Median follow-up: 4.6 years
 Primary outcome: Composite of death from any cause and nonfatal MI

6. POPULATION
Inclusion Criteria
 Stable CAD
 Canadian Cardiovascular Society (CCS) class I, II,
III or stabilized class IV angina
 ≥70% stenosis in at least one coronary artery
 Evidence of MI, defined as:
 ST segment depression
 T wave inversion on the resting EKG
 Inducible ischemia with either exercise or
pharmacologic stress test
 80% stenosis with classic angina without
provocative testing
Exclusion Criteria
 Persistent CCS class IV angina
 Markedly positive treadmill test (significant ST
segment depressions and/or hypotensive
response during stage I of Bruce protocol)
 LVEF <30%
 Refractory CHF
 Cardiogenic shock
 ≥50% left main disease
 Revascularization within the previous 6 months
 Coronary lesions deemed unsuitable for PCI

7. INTERVENTIONS
 Randomly assigned to PCI plus OMT vs. OMT alone
 Both arms received OMT, which included:
 Antiplatelet: aspirin 81-325mg or clopidogrel 75mg daily (if aspirin intolerant); PCI arm received both
 Antiischemic: metoprolol, amlodipine, Isosorbide mononitrate, alone or in combination
 Lisinopril or losartan regardless of LVEF or history of prior MI
 Lipid-lowering: Statins ±ezetimibe to goal LDL 60-85 mg/dl
 Niacin ±fibrates to goal HLD >40 mg/dl and TG <150 mg/dl
 Exercise recommended
 For PCI arm:
 Target-lesion revascularization always attempted
 PCI success seen as normal coronary flow and <50% stenosis in luminal diameter after balloon angioplasty and
<20% after stent, based on visual estimation of angiogram
 Clinical success defined as PCI success without in-hospital MI, emergent CABG, or death

8. CRITICISMS/LIMITATIONS/FUNDING
 Study was 85% males, 86% Caucasians, therefore limited generalizability
 Most patients received bare metal stents because DES not yet approved during study
 Many patients excluded: <10% initially screened patients included in trials
 No stratification by ischemic burden
 Unclear how long patients took clopidogrel or if extended duration of therapy would improve
outcomes in the PCI group
 Unclear if GP IIb/IIIa inhibitors were used
FUNDING:
Department of Veterans Affairs Cooperative Studies Program
Canadian Institutes of Health Research
Several pharmaceutical companies which gave money to Dept. of Veteran affairs

9. BOTTOM LINE
For patients with stable CAD, addition of
PCI to optimal medical therapy DID
NOT reduced risk of death, MI, or other
major cardiovascular events compared
to optimal medical therapy alone.

10. DISCUSSION QUESTIONS
 For a patient with stable angina, according to the
COURAGE trial, what is the best treatment?
 What type of cardiac stent did the majority of
patients in the COURAGE trial receive?
 Why is the COURAGE trial not generalizable to half
the population?

11. DISCUSSION QUESTIONS/ANSWERS
 For a patient with stable angina, according to the COURAGE trial, what is the best treatment?
 ANSWER: Optimal medical therapy (pharmacologic and lifestyle). PCI not recommended.
 What type of cardiac stent did the majority of patients in the COURAGE trial receive?
 ANSWER: Bare metal stents because Drug-eluting stents did not get approved until the last 6 months of the
study
 Why is the COURAGE trial not generalizable to the population?
 ANSWER: The majority of the patients in the study were male (85%)/Caucasians (86%)

12. BOARD-LIKE QUESTION
61yo F, evaluated for substernal chest pain that
occurs with walking up 1 flight of stairs. Exercise
stress nuclear myocardial perfusion study
showed no ST-segment changes but did show
small area of inducible ischemia at the apex with
EF 40%. PMHx includes HTN, HLD, DM2. Meds
are Lisinopril, Aspirin 81, Simvastatin 40,
Metformin, Metoprolol, NTG PRN.
Physical exam:
Afebrile, HRN 61, BP 128/71, RR 14 bpm. BMI 25.
Heart: RRR, no m/r/g
Lungs: Clear
EKG: normal sinus. No ST changes
What is the next step in management of this
patient?
A. Continue optimal medical therapy
B. CT a for possible PE
C. Cardiac catheterization
D. Add another anti-angina drug

13. BOARD-LIKE QUESTION
Educational Objective:
Manage a diabetic patient with stable angina not
controlled with optimal medical therapy
Key Point:
- Although Courage Trial showed that PCI in
addition to optimal medical therapy does not
offer any benefit over optimal medical therapy
alone, this ONLY applies to patients with
stable symptoms
- Patients with uncontrolled angina should still
undergo cardiac cath to evaluate for possible
revascularization
ANSWER
What is the next step in management of
this patient?
A. Continue optimal medical therapy
B. CT a for possible PE
C. Cardiac catheterization
D. Add another anti-angina drug

14. REFERENCES
 Boden WE, et al. "Optimal medical therapy with or without PCI for stable coronary disease". The
New England Journal of Medicine. 2007. 356:1503-16.
 Brain, P. COURAGE. Retrieved March 5, 2017, from https://www.wikijournalclub.org/wiki/COURAGE