ILLUMINATE Trial: Final Results

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ILLUMINATE TrialFinal Results

• Adapted fromBarter et al. N Engl J Med
  20073572109-2122

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ILLUMINATE
Objective

• To assess the efficacy of the cholesterol ester
  transfer protein (CETP) inhibitor torcetrapib
  (Pfizer) on the risk of clinical cardiovascular
  events in patients with history of cardiovascular
  disease or diabetes mellitus

Barter et al. N Engl J Med 20073572109-2122
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ILLUMINATE
Study Design

• Inclusion
• Age 45-75
• History of CVD
• MI
• Stroke
• ACS
• PVD
• Revascularization
• Type 2 DM
• No CVD

• Exclusion
• Unstable medical history
• Life expectancy lt5 yrs
• LDL cholesterol lt100 mg/dL
• CV event during run-in
• Systolic BP gt 140 mmHg
• Or diastolic gt90 mmHg

N15,067
Atorvastatin Placebo N 7,534
Torcetrapib 60mg Atorvastatin N 7,533
Primary Outcomes Major CV events (fatal MI, fatal
CHF, sudden cardiac death, non-fatal MI, stroke,
hospitalized unstable angina)
Secondary Outcomes 1st occurrence of individual
components of the primary outcome, change in LDL,
HDL from baseline
Barter et al. N Engl J Med 20073572109-2122
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ILLUMINATE
Baseline Demographics
Barter et al. N Engl J Med 20073572109-2122
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ILLUMINATE
Baseline Demographics
Barter et al. N Engl J Med 20073572109-2122
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ILLUMINATE
Baseline Demographics
Barter et al. N Engl J Med 20073572109-2122
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ILLUMINATE
Change in Lipids at Month 12
Plt0.001
Plt0.001
Plt0.001
Plt0.001
Total
HDL
LDL
Triglycerides

Absolute change Median change

Cholesterol
Barter et al. N Engl J Med 20073572109-2122
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ILLUMINATE
Percentage Change in Lipids at Month 12
Plt0.001
Plt0.001
Plt0.001
Plt0.001
Total
HDL
LDL
Triglycerides

Absolute change Median change

Cholesterol
Barter et al. N Engl J Med 20073572109-2122
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ILLUMINATE
Change in Blood Pressure at Month 12
Plt0.001
Plt0.001
Barter et al. N Engl J Med 20073572109-2122
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ILLUMINATE
Change in Electrolytes at Month 12
Plt0.001
Plt0.001
Plt0.001
P0.06
Potassium
Sodium
Chloride
Bicarbonate
Barter et al. N Engl J Med 20073572109-2122
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ILLUMINATE
Renal Function at Month 12
Plt0.001
Plt0.001
Creatinine
Estimated Glomerular Filtration Rate
Barter et al. N Engl J Med 20073572109-2122
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ILLUMINATE
Change in Liver Function at Month 12
P0.33
Plt0.001
Plt0.001
Alkaline Phosphatase
Aspartate Aminotransferase
Alanine Aminotransferase
Barter et al. N Engl J Med 20073572109-2122
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ILLUMINATE
Primary Outcomes
HR 1.25 95 CI 1.09-1.44 P0.001
Barter et al. N Engl J Med 20073572109-2122
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ILLUMINATE
Secondary Outcomes
HR 1.35 95 CI 1.13-1.62 P0.001
PNS
HR 1.58 95 CI 1.14-2.19 P0.006
PNS
PNS
Barter et al. N Engl J Med 20073572109-2122
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ILLUMINATE
Post Hoc Analyses Death in Torcetrapib Patients
and Change from Baseline to 1 Month in Select
Measures
Barter et al. N Engl J Med 20073572109-2122
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ILLUMINATE
Post Hoc Analyses Death in Torcetrapib Patients
and Change from Baseline to 1 Month in Select
Measures
Barter et al. N Engl J Med 20073572109-2122
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ILLUMINATE
Post Hoc Analyses Death in Torcetrapib Patients
and Change from Baseline to 1 Month in Select
Measures
Barter et al. N Engl J Med 20073572109-2122
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ILLUMINATE
Conclusions

• After 12 months, treatment with the CETP
  inhibitor torcetrapib was associated with a
  statistically significant
• 72 increase in HDL cholesterol
• 25 increase in composite vascular events
• 58 increase in all-cause mortality
• Possible explanations for increased mortality in
  patients randomized to torcetrapib include
• Generation of dysfunctional or proatherogenic HDL
  cholesterol
• An off-target effect of torcetrapib resulting in
  excess mineralocorticoids and subsequent
  increased blood pressure

Barter et al. N Engl J Med 20073572109-2122