CETP inhibition
CETP inhibitor anacetrapib lowers Lp(a) by cutting its production 41%, a kinetic trial of 39 patients (Arterioscler Thromb Vasc Biol 2017)
Original title: CETP (Cholesteryl Ester Transfer Protein) Inhibition With Anacetrapib Decreases Production of Lipoprotein(a) in Mildly Hypercholesterolemic Subjects
Researchers enrolled 39 participants in a fixed-sequence, double-blind trial to examine how anacetrapib, a CETP inhibitor known to lower Lp(a), achieves this effect. Twenty-nine were randomised to atorvastatin 20 mg/day plus placebo for 4 weeks, then atorvastatin plus anacetrapib 100 mg/day for 8 weeks; 10 others received double placebo for 4 weeks then placebo plus anacetrapib for 8 weeks. Stable isotope kinetic studies were performed in a subset of 12 subjects with Lp(a) above 20 nmol/L and more than 15% Lp(a) reduction. Anacetrapib lowered Lp(a) by 34.1% (P<=0.001) in the complete cohort and 39.6% in the kinetic subset, driven by a 41% reduction in apo(a) production rate with no change in its fractional catabolic rate. The findings show anacetrapib lowers Lp(a) by reducing its production rather than speeding its clearance.
Original abstract
Objective: Lp(a) [lipoprotein (a)] is composed of apoB (apolipoprotein B) and apo(a) [apolipoprotein (a)] and is an independent risk factor for cardiovascular disease and aortic stenosis. In clinical trials, anacetrapib, a CETP (cholesteryl ester transfer protein) inhibitor, causes significant reductions in plasma Lp(a) levels. We conducted an exploratory study to examine the mechanism for Lp(a) lowering by anacetrapib.
Approach And Results: We enrolled 39 participants in a fixed-sequence, double-blind study of the effects of anacetrapib on the metabolism of apoB and high-density lipoproteins. Twenty-nine patients were randomized to atorvastatin 20 mg/d, plus placebo for 4 weeks, and then atorvastatin plus anacetrapib (100 mg/d) for 8 weeks. The other 10 subjects were randomized to double placebo for 4 weeks followed by placebo plus anacetrapib for 8 weeks. We examined the mechanisms of Lp(a) lowering in a subset of 12 subjects having both Lp(a) levels >20 nmol/L and more than a 15% reduction in Lp(a) by the end of anacetrapib treatment. We performed stable isotope kinetic studies using 2H3-leucine at the end of each treatment to measure apo(a) fractional catabolic rate and production rate. Median baseline Lp(a) levels were 21.5 nmol/L (interquartile range, 9.9-108.1 nmol/L) in the complete cohort (39 subjects) and 52.9 nmol/L (interquartile range, 38.4-121.3 nmol/L) in the subset selected for kinetic studies. Anacetrapib treatment lowered Lp(a) by 34.1% (P≤0.001) and 39.6% in the complete and subset cohort, respectively. The decreases in Lp(a) levels were because of a 41% reduction in the apo(a) production rate, with no effects on apo(a) fractional catabolic rate.
Conclusions: Anacetrapib reduces Lp(a) levels by decreasing its production.
Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00990808.
CETP inhibitionmechanismsstatins
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.