COURAGE: Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation Purpose To compare the efficacy of optimal medical therapy (OMT)

COURAGE: Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation

PurposeTo 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.

ReferenceBoden WE, O’Rourke 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 2008;358:1887–1898.


- TRIAL DESIGN -

DesignMulticenter, prospective, randomized trial.

Patients2287 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 <30%, revascularization within the previous 6 months, and coronary anatomy not suitable for PCI.

Primary and secondary endpointsThe primary endpoint was a composite of all-cause mortality and non-fatal myocardial infarction (MI) during a follow-up period of 2.5–7.0 years.

Secondary endpoints included non-fatal MI, hospitalization for acute coronary syndrome, and a composite of death, MI and stroke.


- TRIAL DESIGN continued -

TreatmentFor OMT, all patients received aspirin (81–325 mg/day) or clopidogrel (75 mg/day). All patients received simvastatin alone or in combination with ezetimibe to reduce LDL-cholesterol levels (target of 1.55–2.220 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 + OMTIn 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 considerationsBoth groups received anti-ischemic therapy (metoprolol, amlodipine and/or isosorbide mononitrate) with lisinopril or losartan.


- TRIAL DESIGN continued -

Mean age - years

Male - number (%)

Angina – CCS class (%)

History – number (%)

Baseline characteristics

61.5

979 (85)

OMT + PCI(n=1149)

61.8

968 (85)

OMT(n=1138)

Boden et al. N Eng J Med 2007;356:1–14.

0 135 (12) 148 (13)340 (30) 341 (30)

Previous PCI 174 (15) 185 (16)

IIIII

409 (36)261 (23)

425 (37)221 (19)

Hypertension

Congestive heart failureCerebrovascular diseaseMyocardial infarction

757 (66)367 (32)57 (5)

100 (9)437 (38)

764 (67)399 (35)51 (4)

102 (9)439 (39)

Diabetes

I

Vessels with disease (%)One

Three

361 (31)446 (39)341 (30)

343 (30)439 (39)355 (31)

Two

Proximal LAD disease (%) 360 (31) 417 (37)

Ejection fraction 60.8 60.9


- RESULTS -

Primary endpoint and follow-upAt 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], 0.87–1.27; p=0.62).

Secondary endpointsThere 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, 0.87–1.27; p=0.62)

• Hospitalization for acute coronary syndromes (12.4% vs. 11.8%, respectively; HR, 1.07; 95% CI 0.84–1.37; p=0.56)

• Myocardial infarction (13.2% vs. 12.3%, respectively; HR, 1.13; 95% CI, 0.89–1.43; p=0.33)

Subgroup analysisThe primary endpoint was similar across both groups in patients with multivessel CAD, previous MI and diabetes.


- RESULTS continued -

Years

0 1 2 3 4 5 6 70

0.5

0.6

0.7

0.8

0.9

1.0

Years

0 1 2 3 4 5 6 70

0.5

0.6

0.7

0.8

0.9

1.0

Overallsurvival

Survivalfree ofdeath

from anycause and

myocardialinfarction

HR, 1.05; 95% CI, 0.87–1.27; p=0.62 HR, 0.87; 95% CI, 0.65–1.16; p=0.38


Kaplan-Meier survival curves

PCI

Medical therapy

No. at riskMedical therapyPCI

11381149

959952

638637

192200

10171013

834833

408417

3035

11381149

10291051

717733

302312

10731094

917929

468488

3844

Hospitalization for acutecoronary syndromes

Death alone

Stroke alone

Secondary endpoints


Total non-fatal MI

Revascularization (PCI or CABG)

Patients free from angina at5 years follow-up

12.4

7.6

2.1

13.2

21.1

74


- RESULTS continued -

11.8

8.3

1.8

12.3

32.6

72

PCI + OMTn=1149

OMTn=1149

Hazard ratio(95% CI)

p value

HR, 1.07(95% CI, 0.84–1.37)

0.56

0.19

0.33

<0.001

0.35

HR, 0.87(95% CI, 0.65–1.16)

HR, 1.56(95% CI, 0.80–3.04)

HR, 1.13(95% CI, 0.89–1.43)

HR, 0.60(95% CI, 0.51–0.71)

0.38

Data indicate percentages of patients.


- 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.

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COURAGE: Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation Purpose To compare the efficacy of optimal medical therapy (OMT)