http://www.theheart.org/web_slides/1158009.do A randomized study on determining the efficacy and tolerability of CETP Inhibition with anacetrapib (DEFINE) with the help of 1623 patients with CHD or at high risk for CHD.

1. DEFINE (Determining the Efficacy and
Tolerability of CETP Inhibition with
Anacetrapib)

2. DEFINE (Determining the Efficacy and Tolerability of
CETP Inhibition with Anacetrapib)
C Cannon (Brigham and Women’s Hospital, Boston, MA)
American Heart Association 2010 Scientific Sessions
• Background:
Anacetrapib is a new cholesteryl ester transfer protein (CETP) inhibitor
• Population and treatment:
1623 patients with CHD or at high risk for CHD, baseline LDL-C 50–100 mg/dL
while taking a statin and HDL-C < 60 mg/dL
Randomized to anacetrapib 100 mg or placebo
• Outcome:
Primary end point: change in LDL-cholesterol levels at 24 weeks and safety
and side-effect profile at 76 weeks
Secondary end point: change in HDL-cholesterol level

3. DEFINE: Results
• Anacetrapib significantly decreased LDL-C by 36% and increased HDL-C by
138% when compared with placebo
• SBP, electrolytes, aldosterone, mortality and CV events were similar in both groups
Changes in lipid parameters (mg/dL) in the anacetrapib-treated patients
Variable Baseline Week 24 Week 76
LDL-C 81.2 44.7 48.9
HDL-C 40.5 101.2 102.3
Non–HDL-C 109.7 69.7 73.0
Apolipoprotein B 88.4 70.1 69.6
Apolipoprotein A1 142.5 208.0 203.0
Total cholesterol 150.3 170.8 175.2
Lipoprotein(a) 26.8 14.8 16.4

4. DEFINE: Commentary*
"I think the very exciting thing is that we're entering an era where we have
medications that raise HDL cholesterol."
- Dr Christopher Cannon
"We've gone as far with statins as we can go, and HDL cholesterol is a very
promising target."
-Dr Steven Nissen
"With torcetrapib, we saw the rise in aldosterone levels, which led to the
hypertension in susceptible patients. With anacetrapib, there is no rise in
aldosterone or blood pressure. There are no adverse effects that we can see at all."
- Dr Roger Blumenthal
*All comments from DEFINE: Large effects on LDL and HDL cholesterol with CETP inhibitor
anacetrapib (http://www.theheart.org/article/1151979.do)

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