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Effect of torcetrapib on the progression of coronary atherosclerosis

Steven E Nissen1, Jean-Claude Tardif, Stephen J Nicholls

  • 1Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA. nissens@ccf.org

The New England Journal of Medicine
|March 28, 2007
PubMed

Insights

Torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, significantly raised HDL cholesterol and lowered LDL cholesterol. However, it did not reduce coronary atherosclerosis progression and increased blood pressure.

Area of Science:

  • Cardiovascular Medicine
  • Pharmacology
  • Biochemistry

Background:

  • High-density lipoprotein (HDL) cholesterol levels are inversely correlated with cardiovascular disease (CVD) risk.
  • Torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, elevates HDL cholesterol, but its functional impact on CVD remains unclear.

Purpose of the Study:

  • To evaluate the efficacy of torcetrapib in patients with coronary disease.
  • To assess the impact of torcetrapib on coronary atherosclerosis progression when added to atorvastatin therapy.

Main Methods:

  • 1188 patients with coronary disease received atorvastatin to lower LDL cholesterol.
  • Patients were randomized to atorvastatin monotherapy or atorvastatin plus torcetrapib.
  • Coronary atherosclerosis progression was assessed using intravascular ultrasonography after 24 months in 910 patients.

Main Results:

  • Torcetrapib-atorvastatin therapy increased HDL cholesterol by 61% and decreased LDL cholesterol by 20%, achieving an LDL/HDL ratio below 1.0.
  • A significant increase in systolic blood pressure (4.6 mm Hg) was observed with torcetrapib.
  • No significant difference in the primary endpoint (percent atheroma volume change) was found between groups (P=0.72).

Conclusions:

  • Torcetrapib effectively increased HDL cholesterol and decreased LDL cholesterol but did not significantly reduce coronary atherosclerosis progression.
  • The observed increase in blood pressure and lack of efficacy suggest potential class- or molecule-specific adverse effects.
  • Further research is needed to understand the clinical utility and safety of CETP inhibitors.
Abstract

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