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.

Description:

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.

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

Interpretation:

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. Previous studies of CTEP inhibitors (different agents and different follow-up periods) have shown neutral or hazardous effects on cardiovascular outcomes.

References:

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.

Clinical Topics: Cardiac Surgery, Diabetes and Cardiometabolic Disease, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Prevention, Vascular Medicine, Cardiac Surgery and Arrhythmias, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Interventions and Coronary Artery Disease, Interventions and Vascular Medicine

Keywords: 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 X, Myocardial Infarction, Myocardial Revascularization, Neoplasms, Peripheral Arterial Disease, Primary Prevention, Treatment Outcome, Vascular Diseases


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