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

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

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

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

REVEAL: Primary endpoint RR: 0.91; 95%CI: 0.85-0.97; P=0.004 RR: rate ratio; CI: confidence interval; Bowman L, et al. NEJM 2017

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

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