COURAGE: Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation

1
COURAGE Clinical Outcomes Utilizing
Revascularization and Aggressive Drug Evaluation

• Purpose
• To compare the efficacy of optimal medical
  therapy (OMT) alone versus percutaneous coronary
  intervention (PCI) and OMT in reducing
  cardiovascular risk in patients with stable
  coronary artery disease.
• Reference
• Boden WE, ORourke RA, Teo KK, et al. for the
  COURAGE Trial Research Group. Optimal medical
  therapy with or without PCI for stable coronary
  disease. N Engl J Med 200835818871898.

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COURAGE Clinical Outcomes Utilizing
Revascularization and Aggressive Drug
Evaluation- TRIAL DESIGN -

• Design
• Multicenter, prospective, randomized trial.
• Patients
• 2287 patients who had either stable coronary
  artery disease (CAD) or Canadian Cardiovascular
  Society (CCS) class IV angina that had
  subsequently stabilized.
• Exclusion criteria included persistent CCS class
  IV angina, refractory heart failure or
  cardiogenic shock, classic angina, ejection
  fraction of lt30, revascularization within the
  previous 6 months, and coronary anatomy not
  suitable for PCI.
• Primary and secondary endpoints
• The primary endpoint was a composite of
  all-cause mortality and non-fatal myocardial
  infarction (MI) during a follow-up period of
  2.57.0 years.
• Secondary endpoints included non-fatal MI,
  hospitalization for acute coronary syndrome, and
  a composite of death, MI and stroke.

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COURAGE Clinical Outcomes Utilizing
Revascularization and Aggressive Drug
Evaluation- TRIAL DESIGN continued -

• Treatment
• For OMT, all patients received aspirin (81325
  mg/day) or clopidogrel (75 mg/day). All patients
  received simvastatin alone or in combination with
  ezetimibe to reduce LDL-cholesterol levels
  (target of 1.552.220 mmol/L).
• Exercise, fibrates and/or extended release
  niacin were used to raise HDL-cholesterol levels
  (target 1.03 mmol/L) and to reduce triglyceride
  levels (target of 1.69 mmol/L).
• PCI OMT
• In addition to OMT, complete revascularization
  was performed as necessary, and target-lesion
  revascularization was attempted when appropriate.
• Patients undergoing PCI received aspirin or
  clopidogrel in accordance with the guidelines.
• Other therapeutic considerations
• Both groups received anti-ischemic therapy
  (metoprolol, amlodipine and/or isosorbide
  mononitrate) with lisinopril or losartan.

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COURAGE Clinical Outcomes Utilizing
Revascularization and Aggressive Drug Evaluation
- TRIAL DESIGN continued -
Baseline characteristics

OMT PCI
OMT
(n1138)
(n1149)
Mean age - years
61.5
61.8
Male - number ()
979 (85)
968 (85)
Angina CCS class ()
0
135 (12)
148 (13)
I
340 (30)
341 (30)
II
409 (36)
425 (37)
III
261 (23)
221 (19)
History number ()
Hypertension
757 (66)
764 (67)
367 (32)
Diabetes
399 (35)
Congestive heart failure
57 (5)
51 (4)
Cerebrovascular disease
100 (9)
102 (9)
Myocardial infarction
437 (38)
439 (39)
Previous PCI
174 (15)
185 (16)
Vessels with disease ()
361 (31)
343 (30)
One
446 (39)
Two
439 (39)
Three
341 (30)
355 (31)
Proximal LAD disease ()
360 (31)
417 (37)
Ejection fraction
60.8
60.9
Boden et al. N Eng J Med 2007356114.
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COURAGE Clinical Outcomes Utilizing
Revascularization and Aggressive Drug Evaluation
- RESULTS -

• Primary endpoint and follow-up
• At 4.6 years, the estimated cumulative primary
  event rates were 19.0 in the PCI OMT group,
  and 18.5 in the OMT group (unadjusted hazard
  ratio HR in PCI group, 1.05 95 confidence
  interval CI, 0.871.27 p0.62).
• Secondary endpoints
• There were no significant differences between
  the PCI OMT group and the OMT group in terms of
  the following
• Composite of death, myocardial infarction and
  stroke (20 vs. 19.5, respectively HR, 1.05
  95 CI, 0.871.27 p0.62)
• Hospitalization for acute coronary syndromes
  (12.4 vs. 11.8, respectively HR, 1.07 95 CI
  0.841.37 p0.56)
• Myocardial infarction (13.2 vs. 12.3,
  respectively HR, 1.13 95 CI, 0.891.43
  p0.33)
• Subgroup analysis
• The primary endpoint was similar across both
  groups in patients with multivessel CAD, previous
  MI and diabetes.

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COURAGE Clinical Outcomes Utilizing
Revascularization and Aggressive Drug Evaluation
- RESULTS continued -
Kaplan-Meier survival curves
PCI
Medical therapy
No. at risk Medical therapy PCI
Boden et al. N Eng J Med 2007356114.
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COURAGE Clinical Outcomes Utilizing
Revascularization and Aggressive Drug Evaluation
- RESULTS continued -
Secondary endpoints

PCI OMTn1149
OMTn1149
Hazard ratio(95 CI)
p value
Hospitalization for acutecoronary syndromes
HR, 1.07(95 CI, 0.841.37)
12.4
11.8
0.56
HR, 0.87(95 CI, 0.651.16)
Death alone
0.38
7.6
8.3
HR, 1.56(95 CI, 0.803.04)
Stroke alone
0.19
2.1
1.8
HR, 1.13(95 CI, 0.891.43)
Total non-fatal MI
0.33
13.2
12.3
HR, 0.60(95 CI, 0.510.71)
Revascularization (PCI or CABG)
21.1
32.6
lt0.001
Patients free from angina at5 years follow-up
74
72
0.35
Data indicate percentages of patients.
Boden et al. N Eng J Med 2007356114.
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COURAGE Clinical Outcomes Utilizing
Revascularization and Aggressive Drug Evaluation
- SUMMARY -

• Compared with OMT alone, PCI OMT did not
  reduce the primary composite endpoints of
  all-cause mortality and non-fatal MI, and it did
  not reduce the incidence of major cardiovascular
  events.
• In terms of secondary endpoints, there was no
  significant difference between the groups.
• However, PCI OMT did reduce the occurrence of
  angina in comparison with OMT alone.
• The results of this study are in agreement with
  the guidelines stating that PCI can be safely
  conducted in patients with stable coronary artery
  disease, provided that aggressive medical therapy
  is also maintained.