1. REVEAL: Randomized Evaluation of the Effects of Anacetrapib through Lipid Modification
First time a CETP inhibitor shows reduction of serious CV events
Bowman L, Hopewell JC, Chen F, et al. Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease. NEJM 2017

2. REVEAL: Background and Objective
CETP inhibition with anacetrapib decreases LDL-c and increases HDL-c levels, but there is no evidence of a beneficial effect on CV outcomes.
Study objective
The REVEAL study was designed to assess the clinical efficacy and safety of anacetrapib versus placebo in patients with atherosclerotic vascular disease, who were receiving effective statin therapy.
CETP: Cholesteryl Ester Transfer Protein; LDL-c: low density lipoprotein cholesterol; HDL-c: high density lipoprotein cholesterol
Bowman L, et al. NEJM 2017

3. REVEAL: Inclusion and exclusion criteria
Inclusion criteria
Age > 50 years
Total cholesterol <155 mg/dL (<4.0 mmol/L)
History of MI, or CVD, or PAD, or DM with symptomatic CHD
Exclusion criteria
ACE or stroke <3 months before randomization
Planned coronary revascularization
Clinically significant liver, kidney, inflammatory muscle, or other disease
Current treatment with a fibrate, niacin, or any drug contraindicated with anacetrapib or atorvastatin, or history of adverse reaction to a statin
Known poor adherence
MI: myocardial infarction; CVD: cerebrovascular disease; PAD: peripheral arterial disease; DM; diabetes mellitus; CHD: coronary heart disease; ACE: acute coronary event
Bowman L, et al. NEJM 2017

4. REVEAL: Study design
Patients with a history of CAD/CVD/PAD/DM on atorvastatin
with Tc<155 mg/dL (N=30,449)
Anacetrapib
100 mg/day
N=15,225
Placebo
N=15,224
The primary outcome was the first occurrence of coronary death, myocardial infarction, or coronary revascularization.
Secondary outcomes were major atherosclerotic events (a composite of coronary death, myocardial infarction, or presumed ischemic stroke), presumed ischemic stroke (i.e., not
known to be hemorrhagic), and major vascular events (a composite of major coronary events or presumed ischemic stroke).
Median follow-up: 4.1 years
Primary endpoint: composite of coronary death, MI, or coronary revascularization
CAD: coronary artery disease; CVD: cerebrovascular disease; PAD: peripheral arterial disease; DM: diabetes mellitus; Tc: total cholesterol; MI: myocardial infarction
Bowman L, et al. NEJM 2017

5. REVEAL: Primary endpoint
RR: 0.91; 95%CI: ; P=0.004
RR: rate ratio; CI: confidence interval;
Bowman L, et al. NEJM 2017

6. REVEAL: Results 5.3% (N=510) 6.0% (N=571) -0.6% 0.05 11.5% (N=1,344)
Mean values (mg/dl)
Anacetrapib (N=15,225)
Placebo (N=15,224)
Absolute Difference*
Relative Difference
Mean non-HDL-c 79 96
-17
-18%
Mean HDL-c 85 42
+43
+104%
Anacetrapib (N=15,225)
Placebo (N=15,224)
Difference
P value
New-onset DM
5.3%
(N=510)
6.0% (N=571)
-0.6%
0.05
New-onset KD
11.5% (N=1,344)
10.6% (N=1,236)
+0.84
0.04
(*) The absolute difference is the value in the anacetrapib group minus the value in the placebo group. P<0.001 for all comparisons.
DM: diabetes mellitus; KD: kidney disease (defined as eGFR <60mL/min/1.73m2);
Bowman L, et al. NEJM 2017

7. REVEAL: Conclusions
Compared with placebo, anacetrapib 100 mg daily given on top of atorvastatin to patients with documented vascular disease led to:
a significant 9% proportional reduction in major coronary events
a median increase of HDL-c of 43 mg/dL
a median reduction of non-HDL-c of 17 mg/dL
a small reduction in the risk of new-onset diabetes mellitus
increased new-onset kidney disease
no excess side-effects, mortality, or cancer
Bowman L, et al. NEJM 2017