Prevention: Results of the ILLUMINATE Trial Released at AHA 2007
November 6, 2007 By Scott P. Williams 
Orlando, FL: The results of the ILLUMINATE trial suggest that patients with a history of cardiovascular disease (CVD) who are treated with torcetrapib face an increased risk of death and cardiac events.  The results were announced at the American Heart Associations Scientific Sessions.
The research team hypothesized that torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, would decrease the risk of clinical cardiovascular events by lowering the patients LDL cholesterol level and raising their HDL cholesterol levels.  To test this hypothesis the researchers conducted a prospective, randomized, multi-center, double-blind clinical trial.  Men and women spanning the ages of 45 to 75 years old were eligible to participate in the trial if they displayed symptoms of CVD (MI, stroke, ACS, UA, PVD, cardiac revascularization) 30 days to 5 years prior to enrollment.  Diabetic patients without prior CVD were also eligible for the study.  Upon the completion of 4 to 10 weeks of lifestyle counseling treatment with atorvastatin (as necessary) to reach an LDL cholesterol level of less than 100 mg per deciliter, patients were randomized to receive either atorvastatin and 60 mg torcetrapib (n=7533) or atorvastatin and placebo (n=7534).  The median follow up for both groups of patients was 550 days.
The primary endpoint of ILLUMINATE was the occurrence of a major cardiovascular event, which was defined as any of the following: death from coronary heart disease, nonfatal MI, stroke, and hospitalization for UA.  Secondary endpoints were the time to occurrence of each individual component of the primary endpoint, the time to all cause death, and change in HDL and LDL cholesterol levels.
A 72.1% increase in HDL cholesterol and a 24.9% decrease in LDL cholesterol, as compared with baseline, was displayed by the patients who received torcetrapib (p<0.001).  In the same group of patients a 5.4 mm HG increase in systolic blood pressure, increases in serum bicarbonate, aldosterone, and sodium, and a decrease in serum potassium were all observed (p<0.001).
The patients who received torcetrapib demonstrated an increased risk of major cardiovascular events (6.2% vs. 5.0%, HR 1.25, p = 0.001).  Additionally, the rate of all-cause mortality was higher in the group of patients receiving torcetrapib (1.2% vs. 0.8%, HR 1.58, p = 0.006).  The authors noted that post hoc analyses demonstrated that patients who were treated with torcetrapib and had a reduction in serum potassium or an increase in serum bicarbonate greater than the median level of change displayed an increased risk of death.
Although treatment with torcetrapib was associated with an increase in HDL and LDL cholesterol levels, it was also associated with an increased risk of mortality and morbidity.  This risk, coupled with an increased risk of cardiac events in patients receiving torcetrapib, led to the ILLUMINATE trial being terminated early on the recommendation of the trials independent steering committee.  Further research and analysis is required to determine if the inhibition of CETP is cardioprotective.
This study was supported by Pfizer.
References
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