Evacetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, substantially increased high-density lipoprotein (HDL) cholesterol whilst decreasing low-density lipoprotein (LDL) cholesterol, in a trial published in the Journal of the American Medical Association.
In the trial, a team from the Cleveland Clinic in Ohio, US randomised 398 patients with dyslipidaemia to receive either placebo, evacetrapib (30mg, 100mg or 500mg daily), or a statin with or without evacetrapib (100mg daily).
After 12 weeks, patients receiving evacetrapib as monotherapy experienced average reductions in LDL cholesterol of up to 36%, or 1.32mmol/L. Additionally, those on the highest dose of evacetrapib saw a rise in HDL cholesterol of up to 129%, or 1.69mmol/L.
By contrast, LDL cholesterol rose by 4% and HDL cholesterol fell by 3% in the placebo group.
LDL cholesterol decreased to a greater extent among patients receiving evacetrapib 100mg in combination with statin therapy, although researchers found no additional rise in HDL cholesterol.
They concluded that 'the findings suggest that evacetrapib could be administered with statins and may yield potentially clinically important incremental effects on lipoproteins'.
'However, development of drugs that increase HDL cholesterol levels has been challenging and fraught with failures,' the researchers noted.
Development of the first CETP inhibitor, torcetrapib, was terminated prematurely when the ILLUMINATE study revealed that it increased the risks of mortality and morbidity. Nevertheless, confidence is growing that other candidates, such as evacetrapib, anacetrapib and dalcetrapib, may be free of this effect.