Comparison of low-density lipoprotein cholesterol equations in patients with dyslipidaemia receiving cholesterol ester transfer protein inhibition

AIMS: Low-density lipoprotein (LDL-C) lowering is imperative in cardiovascular disease prevention. We aimed to compare accuracy of three clinically-implemented LDL-C equations in a clinical trial of cholesterol ester transfer protein (CETP) inhibition. METHODS AND RESULTS: Men and women aged 18–75 years with dyslipidaemia were recruited from 17 sites in the Netherlands and Denmark. Patients were randomly assigned to one of nine groups using various combinations of the CETP inhibitor TA-8995 (obicetrapib), statin therapy, and placebo. In pooled measurements over 12 weeks, we calculated LDL-C by the Friedewald, Martin/Hopkins, and Sampson equations, and compared values with preparative ultracentrifugation (PUC) LDL-C overall and with a special interest in the low LDL-C/high triglycerides subgroup. There were 242 patients contributing 921 observations. Overall median LDL-C differences between estimates and PUC were small: Friedewald, 0.00 (25(th), 75(th): −0.10, 0.08) mmol/L [0 (−4, 3) mg/dL]; Martin/Hopkins, 0.02 (−0.08, 0.10) mmol/L [1 (−3, 4) mg/dL]; and Sampson, 0.05 (−0.03, 0.15) mmol/L [2 (−1, 6) mg/dL]. In the subgroup with estimated LDL-C <1.8 mmol/L (<70 mg/dL) and triglycerides 1.7–4.5 mmol/L (150−399 mg/dL), the Friedewald equation underestimated LDL-C with a median difference versus PUC of −0.25 (−0.33, −0.10) mmol/L [−10 (−13, −4) mg/dL], whereas the median difference by Martin/Hopkins was 0.00 (−0.08, 0.10) mmol/L [0 (−3, 4) mg/dL] and by Sampson was −0.06 (−0.13, 0.00) mmol/L [−2 (−5, 0) mg/dL]. In this subgroup, the proportion of LDL-C observations <1.8 mmol/L (<70 mg/dL) that were correctly classified compared with PUC was 71.4% by Friedewald vs. 100.0% by Martin/Hopkins and 93.1% by Sampson. CONCLUSION: In European patients with dyslipidaemia receiving a CETP inhibitor, we found improved LDL-C accuracy using contemporary equations vs. the Friedewald equation, and the greatest accuracy was observed with the Martin/Hopkins equation. REGISTRATION: ClinicalTrials.gov, NCT01970215