Anacetrapib
The Friedewald formula underestimates LDL-C by 12 mg/dl after anacetrapib treatment, likely from VLDL-C overestimation (J Lipid Res 2013)
Original title: Measurement of LDL-C after treatment with the CETP inhibitor anacetrapib
Since Friedewald-formula LDL-C estimation is known to be inaccurate when triglycerides are elevated or VLDL particle composition is altered, this study tested whether CETP inhibitor treatment similarly distorts LDL-C measurement. Pre- and post-treatment serum from 280 of the 811 patients treated with anacetrapib in the DEFINE study were assayed by the Friedewald formula, the Roche and Genzyme direct methods, and compared against the beta-quantification reference method. After 24 weeks of anacetrapib, mean LDL-C by the Friedewald formula, Roche direct method, and Genzyme direct method deviated from the reference method by -12.2 plus or minus 7.5, -10.2 plus or minus 6.6, and -10.8 plus or minus 8.8 mg/dl respectively, all underestimating LDL-C. The Friedewald bias appeared driven by overestimation of VLDL cholesterol via the triglyceride-divided-by-5 term, and the clinical significance of these measurement discrepancies awaits comprehensive lipid and cardiovascular outcome data from ongoing phase III anacetrapib trials.
Original 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.
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Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.