Measurement of LDL-C after treatment with the CETP inhibitor anacetrapib.

Abstract:

:Estimation of low-density lipoprotein cholesterol (LDL-C) using the Friedewald (FR) formula is often inaccurate when triglycerides are elevated or VLDL particle composition is altered. We hypothesized that LDL-C estimation by the FR formula and other measurement methods might also be inaccurate in individuals treated with a cholesteryl ester transfer protein (CETP) inhibitor. An assay comparison study was conducted using pre and posttreatment serum samples from 280 of the 811 patients treated with the CETP inhibitor anacetrapib in the DEFINE study (determining the efficacy and tolerability of CETP inhibition with anacetrapib). After 24 weeks of treatment with anacetrapib, mean LDL-C values by FR formula, Roche direct method (RDM) and Genzyme direct method (GDM) deviated from that measured by the β-quantification (BQ) reference method by -12.2 ± 7.5, -10.2 ± 6.6, -10.8 ± 8.8 mg/dl, respectively. After treatment with anacetrapib, the FR formula and detergent-based direct methods provided lower LDL-C values than those obtained by the BQ reference method. The bias by the FR formula appeared to be due to an overestimation of VLDL-C by the TG/5 component of the formula. Evaluation of the clinical significance of these findings awaits comprehensive lipid and cardiovascular outcome data from ongoing Phase III clinical studies of anacetrapib.

journal_name

J Lipid Res

authors

Davidson M,Liu SX,Barter P,Brinton EA,Cannon CP,Gotto AM Jr,Leary ET,Shah S,Stepanavage M,Mitchel Y,Dansky HM

doi

10.1194/jlr.M032615

subject

Has Abstract

pub_date

2013-02-01 00:00:00

pages

467-72

issue

2

eissn

0022-2275

issn

1539-7262

pii

jlr.M032615

journal_volume

54

pub_type

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