Evacetrapib Raises HDL and Lowers LDL — but Then What?

The cholesterol ester transfer protein inhibitor evacetrapib had very favorable lipid effects, but the trial was small and lasted only 12 weeks.


Epidemiologic data clearly show an inverse correlation between high-density lipoprotein (HDL) cholesterol levels and coronary artery disease (CAD). Yet, few drugs are known to increase HDL levels, and achieving definitive improvement in clinical outcomes with HDL-raising agents remains elusive. The AIM-HIGH trial was halted when raising HDL levels with niacin failed to show any clinical benefit (JW Gen Med Jun 7 2011); data from the HPS-2-THRIVE trial of niacin are forthcoming. Raising HDL levels via cholesterol ester transfer protein (CETP) inhibition initially showed promise, but the ILLUMINATE trial of the CETP inhibitor torcetrapib was stopped early because of increased mortality in the study-drug arm (JW Cardiol Nov 5 2007).

Investigators have now conducted a manufacturer-funded study of the CETP inhibitor evacetrapib. They randomized 398 patients without CAD but with dyslipidemia (mean HDL, 55 mg/dL; mean low-density lipoprotein [LDL] cholesterol, 144 mg/dL) to receive placebo alone; evacetrapib monotherapy (at 30 mg, 100 mg, or 500 mg per day); evacetrapib (100 mg daily) in combination with one of three daily statin regimens (40-mg simvastatin, 20-mg atorvastatin, or 10-mg rosuvastatin); or one of the three statin regimens alone. Treatment lasted 12 weeks.

Alone, 500-mg evacetrapib safely yielded a 132% increase in the mean HDL level and a 40% decrease in the mean LDL level, without adverse effects on blood pressure, aldosterone levels, or liver function. The combination of a statin with evacetrapib lowered LDL levels further, as expected, but did not raise HDL levels beyond what evacetrapib alone achieved.


Citation(s):

Nicholls SJ et al. Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on HDL and LDL cholesterol. JAMA 2011 Nov 16; 306:2099.

Cannon CP. High-density lipoprotein cholesterol as the holy grail. JAMA 2011 Nov 16; 306:2153.