Randomized Evaluation of the Effects of Anacetrapib Through Lipid Modification - HPS3/TIMI55-REVEAL

Contribution To Literature:

The HPS3/TIMI55-REVEAL trial showed that anacetrapib was superior to placebo at preventing adverse cardiac events.


The goal of the trial was to evaluate the cholesteryl ester transfer protein (CTEP) inhibitor anacetrapib compared with placebo among patients with stable atherosclerosis.

Study Design

  • Randomized
  • Parallel
  • Placebo
  • Blinded

Patients with stable atherosclerosis were randomized to anacetrapib 100 mg daily (n = 15,225) versus placebo (n = 15,224).

  • Total number of enrollees: 30,449
  • Duration of follow-up: mean 4.1 years
  • Mean patient age: 67 years
  • Percentage female: 16%
  • Percentage with diabetes: 37%

Inclusion criteria:

  • At least 50 years of age with history of myocardial infarction (MI), cerebrovascular disease, peripheral artery disease, or diabetes with symptomatic coronary heart disease
  • Receiving intensive atorvastatin therapy

Exclusion criteria:

  • Acute coronary syndrome or stroke within the last 3 months
  • Planned coronary revascularization
  • Severe liver, kidney, or inflammatory muscle disease
  • Current treatment with fibrate or niacin

Other salient features/characteristics: 

  • Mean low-density lipoprotein cholesterol: 61 mg/dl
  • Mean high-density lipoprotein cholesterol: 40 mg/dl

Principal Findings:

The primary outcome, incidence of coronary death, MI, or coronary revascularization, occurred in 10.8% of the anacetrapib group versus 11.8% of the placebo group (p = 0.004). The benefit of anacetrapib appeared to emerge after ≥3 years of treatment. Findings were similar among those with diabetes versus those without diabetes. There was no difference in the primary outcome according to ADCY9 genotype.

Secondary outcomes:

  • Coronary death: 2.5% with anacetrapib vs. 2.8% with placebo (p = 0.25).
  • MI: 4.4% with anacetrapib vs. 5.1% with placebo (p = 0.007).
  • No difference in the incidence of cancer or adverse events between treatment groups
  • New-onset diabetes: 5.3% with anacetrapib vs. 6.0% with placebo (p = 0.05)


Among patients with stable atherosclerosis on intensive statin therapy, anacetrapib was effective at preventing adverse cardiac events compared with placebo. Coronary death was similar; however, MI was reduced in the anacetrapib group. It appeared that benefit from anacetrapib emerged after ≥3 years of treatment. Findings were similar among those with and without diabetes. Previous studies of CTEP inhibitors (different agents and different follow-up periods) have shown neutral or hazardous effects on cardiovascular outcomes.


Presented by Dr. Jemma Caroline Hopewell at the American College of Cardiology Annual Scientific Session (ACC 2019), New Orleans, LA, March 18, 2019.

Presented by Dr. Louise Bowman at the American Heart Association Annual Scientific Sessions (AHA 2017), Anaheim, CA, November 13, 2017.

The HPS3/TIMI55-REVEAL Collaborative Group. Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease (REVEAL). N Engl J Med 2017;377:1217-27.

Presented by Dr. Martin Landray at the European Society of Cardiology Congress, Barcelona, Spain, August 29, 2017.

Keywords: ACC Annual Scientific Session, ACC19, AHA17, AHA Annual Scientific Sessions, Atherosclerosis, Cerebrovascular Disorders, Cholesterol Ester Transfer Proteins, Cholesterol, LDL, Cholesterol, HDL, Coronary Artery Disease, Diabetes Mellitus, Dyslipidemias, ESC Congress, ESC2017, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Metabolic Syndrome, Myocardial Infarction, Myocardial Revascularization, Neoplasms, Peripheral Arterial Disease, Primary Prevention, Treatment Outcome, Vascular Diseases

< Back to Listings