COURAGE TRIAL

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COURAGE TRIAL Clinical Outcomes Utilizing
Revascularization and Aggressive Drug
Evaluation (Veterans Affairs Cooperative Studies
Program no. 424)
Presented by Dr. Shrinivasan R.
Iyenger Dietitian Nandini Panchamiya
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Global Mortality and Burden of Disease
Attributable to CVD
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CHDThe Response To Injury Hypothesis
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Average values of various measures of obesity in
South Asians/ Asian Indians and other ethnic
groups
Parameters Rural Urban Urban slums Migrant White Caucasians Blacks Mexican Americans
BMI 19.6 20.9 22.4 24.7 26.3 28.5 25.7
body fat 20.4 24.4 28.2 33.1 26.6 29.7 48.8
Waist circumference (cm) 79.4 83.7 85.2 83.7 91.3 83.9 94.5
Waist hip ratio 0.87 0.92 0.87 0.92 0.91 0.86 0.92
 
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Characteristics of Asian Indian Phenotype
Greater ethnic/ genetic susceptibility to type 2
diabetes
Lower threshold for BMI
? inflammatory markers CRP
? serum insulin levels/insulin resistance
? abdominal obesity and abdominal fat
ASIAN INDIAN PHENOTYPE
Characteristic dyslipidemia ? HDL-C, ? TG ?
small dense LDL
? levels of adiponectin
? prevalence of type 2 diabetes and CAD
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• Introduction
• More than 1 million percutaneous coronary
  interventions (PCIs) are performed in the USA
  each year, the great majority of which are
  performed electively in patients with stable
  coronary artery disease(CAD).
• PCI in patients with acute coronary syndrome
  (ACS) has been shown to reduce the incidence of
  death and myocardial infarction (MI).
• However, the effects of PCI in patients with
  stable CAD have not been well studied, with prior
  studies in this patient population suggesting
  that PCI only reduces the frequency of angina and
  improves short-term exercise performance with no
  impact on mortality.

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Background for study Major improvements in
medical therapy and percutaneous coronary
intervention (PCI) for coronary heart disease
have occurred during the past decade, but no
randomized trial has compared these 2 strategies
for the hard clinical end points of death or
myocardial infarction nor have earlier studies
incorporated the use of coronary stents and
aggressive multifaceted medical therapy during
long-term follow-up.
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• Study Design
• Multicenter, randomized, controlled trial of
  patients with documented myocardial ischemia and
  angiographically confirmed single or multivessel
  CAD.
• A total of 2287 patients screened at 50 centers
  in the USA and Canada were randomized to PCI (n
  1149) or to Optimal Medical Therapy (OMT) (n
  1138).

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• Study Design continue
• Patients were followed for 2.5-7.0 years (mean,
  4.6 years).
• Patients with 1-, 2-, or 3-vessel disease (gt 70
  visual stenosis of proximal segment), with
  anatomy suitable for PCI, and Canadian
  Cardiovascular Society (CCS) class I-III angina
  were enrolled in the study.
• Patients with unstable angina, post-MI,
  revascularization within the last 6 months,
  cardiogenic shock, or heart failure were
  excluded.
• Baseline clinical and angiographic
  characteristics were well balanced between the 2
  groups

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Methods Medical therapy in both groups is
guideline-driven and includes aspirin,
clopidogrel, simvastatin (low-density lipoprotein
cholesterol target 60-85 mg/dL), long-acting
metoprolol and/or amlodipine, lisinopril or
losartan, and long-acting nitrates, as well as
lifestyle interventions. More than half of all
patients in the PCI arm were treated with 1 stent
and 41 received 2 stents.
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Methods continue

• Quality of life was assessed with 3
  questionnaires
• The Seattle Angina Questionnaire (SAQ)
• RAND 36-Item Health Survey
• Utility by Standards Gamble
• Data were collected at 1, 3, 6, and 12 months,
  and then annually.
• An incremental cost-efficacy analysis was
  calculated as the additional cost of PCI divided
  by the gain in life-years and quality-adjusted
  life-years (QALYs). QALYs were calculated by
  multiplying survival by utility.

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Hypothesis PCI plus aggressive medical therapy
(projected event rate 16.4) will be superior to
aggressive medical therapy alone (projected event
rate 21) during a 2.5- to 7-year (median of 5
years) follow-up. Primary PCI would reduce
all-cause mortality or nonfatal MI relative to
Optimal Medical Therapy (OMT) alone. Secondary
PCI would yield superior outcomes related to
resource utilization and quality-of-life outcomes.
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• End point
• Primary Death or nonfatal MI.
• Secondary
• Death, MI, or stroke
• Hospitalization for biomarkers
• Cost, resource utilization
• Quality of life, including angina and
• Cost-effectiveness.

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• Results of Primary Hypothesis
• After a mean follow-up of 4.6 years, there was
  no difference in the rate of freedom from death
  of any cause or nonfatal MI between the PCI and
  OMT-alone groups (19.0 vs 18.5, respectively P
  62).
• There were also no differences in the individual
  rates of all-cause mortality, MI, stroke, or
  hospitalization for ACS

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• Results of Primary Hypothesis continue
• The number of patients in the PCI group who
  underwent revascularization was significantly
  lower than the number of first procedures
  performed in the OMT group, at an average of 10
  and 11 months, respectively (21.1 vs 32.6 P
  lt001).
• In addition, freedom from angina was higher in
  the PCI group than OMT alone at 1- and 3-year
  follow-up by 5 years, the rates were similar
  between the 2 groups.

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Freedom from angina
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• Conclusions Primary Hypothesis
• As an initial management strategy in patients
  with stable coronary artery disease, PCI did not
  reduce the risk for death, MI, or other major
  cardiovascular events when added to OMT.
• PCI resulted in better angina relief during most
  of the follow-up period, but OMT was also
  effective, with no between-group difference in
  angina-free status at 5 years.

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• Conclusions Primary Hypothesis continue
• PCI can be safely deferred in patients with
  stable CAD, even in those with extensive,
  multivessel involvement and inducible ischemia,
  provided that intensive, multifaceted OMT is
  instituted and maintained.
• OMT and aggressive management of multiple
  treatment targets without initial PCI can be
  implemented safety in the majority of patients
  with stable CAD, 2/3rds of whom may not require
  even a first revascularization during long-term
  follow-up.

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• Results of Secondary Hypothesis Quality of life
  (QOL)
• At baseline, there was no difference between the
  2 groups in SAQ scores that measured physical
  limitations, angina frequency, and quality of
  life.
• However, evidenced as early as 3 months and
  sustained out to 36 months, patients in the PCI
  group had higher SAQ scores, suggesting improved
  status in all measures studied.
• RAND 36 scores were higher in the PCI group, but
  by 24 months, the difference was not significant.

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• Results of Secondary Hypothesis Resource
  utilization
• At each follow-up period, cost were
  significantly lower with OMT than with PCI (P
  lt0001).
• There was no difference in utility between the 2
  groups at any time during follow-up.
• The difference in calculated QALYs was 0.024,
  equating to about 8 days. This difference
  translated into a cost of 217,000 per QALY
  gained.
• Given that the cost-effective benchmark for such
  therapies is 50,000, the overall cost of QALY
  gained suggests that PCI would only be considered
  a cost-effective approach in lt 1 of patients.

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• Conclusions Secondary Hypothesis
• Compared with OMT alone, PCI plus OMT is
  associated with improved QOL measures over
  long-term follow-up.
• PCI plus OMT as a first-choice therapy for stable
  CAD is not cost-effective compared with OMT alone.

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• Viewpoint
• COURAGE is a landmark trial in stable angina
  patients with CAD.
• The results reinforce that OMT can be as
  effective safe as PCI in the prevention of hard
  endpoints, such as death, MI, stroke.
• However, PCI provided better anginal relief in
  the initial years of follow-up.
• Evaluating QOL and cost-effectiveness, provides
  important information on how we treat our
  patients.

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• Viewpoint
• The study showed that PCI OMT does a better
  job in controlling physical limitation, angina,
  and improves QOL, but at a significantly higher
  cost.
• These results have spawned considerable
  attention, and at times, controversy, over the
  way that we treat patients with stable CAD.
• The results are telling, but are they
  sufficiently conclusive to deny early PCI in all
  stable patients?

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Thank You