title: 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.
authors.affiliation: Pritzker School of Medicine, University of Chicago, Chicago, IL, USA. mdavidso@medicine.bsd.uchicago.edu
authors.forename: Michael
authors.initials: M
authors.lastname: Davidson
authors.forename: Sherry Xueyu
authors.initials: SX
authors.lastname: Liu
authors.forename: Philip
authors.initials: P
authors.lastname: Barter
authors.forename: Eliot A
authors.initials: EA
authors.lastname: Brinton
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Gotto
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: Leary
authors.forename: Sukrut
authors.initials: S
authors.lastname: Shah
authors.forename: Michael
authors.initials: M
authors.lastname: Stepanavage
authors.forename: Yale
authors.initials: Y
authors.lastname: Mitchel
authors.forename: Hayes M
authors.initials: HM
authors.lastname: Dansky
mesh_terms: D000368:Aged; D001774:Blood Chemical Analysis / Q000379:methods* / Q000592:standards; D011232:Chemical Precipitation; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors*; D008076:Cholesterol, HDL / Q000097:blood / Q000302:isolation & purification; D008078:Cholesterol, LDL / Q000097:blood* / Q000302:isolation & purification; D002986:Clinical Trials as Topic; D016264:Dextran Sulfate / Q000737:chemistry; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D023303:Oxazolidinones / Q000494:pharmacology*; D012015:Reference Standards; D013997:Time Factors; D014461:Ultracentrifugation
chemical_list: D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D023303:Oxazolidinones; D016264:Dextran Sulfate; C530884:anacetrapib