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Cholesteryl ester transfer protein inhibition to reduce cardiovascular risk: Where are we now?

Philip Barter1, Kerry-Anne Rye

  • 1The Heart Research Institute, 7 Eliza Street, Newtown, Sydney 2042, Australia. barterp@hri.org.au

Trends in Pharmacological Sciences
|November 18, 2011
PubMed

Insights

Cholesteryl ester transfer protein (CETP) inhibitors aim to raise HDL-C for cardiovascular disease prevention. Newer CETP inhibitors are being tested in clinical trials to re-evaluate their efficacy and safety.

Area of Science:

  • Cardiovascular medicine
  • Pharmacology
  • Lipid metabolism

Background:

  • Elevated low-density lipoprotein-cholesterol (LDL-C) and reduced high-density lipoprotein-cholesterol (HDL-C) are key risk factors for cardiovascular disease (CVD).
  • Cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl esters from HDL to other lipoproteins, influencing lipid profiles.
  • Inhibiting CETP is a strategy to increase HDL-C levels and potentially reduce CVD risk.

Purpose of the Study:

  • To re-evaluate the anti-atherogenic potential of CETP inhibitors.
  • To assess the safety and efficacy of CETP inhibitors that lack the adverse off-target effects of earlier agents like torcetrapib.

Main Methods:

  • Clinical outcome trials are underway with novel CETP inhibitors, specifically dalcetrapib and anacetrapib.
  • These trials aim to determine if CETP inhibition, without torcetrapib's off-target effects, proves beneficial in preventing cardiovascular events.

Main Results:

  • Previous CETP inhibitor torcetrapib was associated with increased mortality and cardiovascular events, possibly due to off-target effects.
  • Current trials with dalcetrapib and anacetrapib are designed to isolate the effects of CETP inhibition itself.

Conclusions:

  • The hypothesis that CETP inhibitors are anti-atherogenic is being re-examined with newer agents.
  • Ongoing clinical trials will provide crucial data on the cardiovascular benefits and risks of selective CETP inhibition.

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