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. Findings were similar among those with diabetes versus those without diabetes.

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)

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. 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.

References:

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.

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

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


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