Martin SS, et al. - In the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk (FOURIER) trial, researchers determined the accuracy of 2 different methods for estimating low-density lipoprotein cholesterol (LDL-C) levels (Martin/Hopkins and Friedewald) vs gold standard preparative ultracentrifugation (PUC) in patients with low LDL-C levels. They observed a more closer approximation of the Martin/Hopkins method vs Friedewald method to gold standard PUC for LDL-C estimation in patients achieving low LDL-C with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition. They also noted that the Martin/Hopkins method could prevent undertreatment because of LDL-C underestimation by the Friedewald method.

Methods

• In the FOURIER trial, which represents a randomized clinical trial, researchers tested evolocumab vs placebo added to statin therapy in 27,564 patients with stable atherosclerotic cardiovascular disease.
• They evaluated LDL-C levels of the patients at baseline, 4 weeks, 12 weeks, 24 weeks, and every 24 weeks thereafter, and measured directly by PUC when the level was less than 40 mg/dL per the Friedewald method (calculated as non–HDL-C level - triglycerides/5).
• The Martin/Hopkins method involved determination of patient-specific ratios of triglycerides to very low-density lipoprotein cholesterol (VLDL-C) ratios and their use to estimate VLDL-C, which was subtracted from the non–HDL-C level to obtain the LDL-C level.
• Main outcomes and measures included low-density lipoprotein cholesterol calculated by the Friedewald and Martin/Hopkins methods, with PUC as the reference method.

Results

• With mean (SD) age 62.7 (9.0) years; 2,885 of the 12,742 patients included in this study were women (22.6%).
• Data showed that a total of 56,624 observations from 12,742 patients had Friedewald, Martin/Hopkins, and PUC LDL-C measurements.
• The median difference from PUC LDL-C levels For Martin/Hopkins LDL-C levels and for Friedewald LDL-C levels, the estimated median difference from PUC LDL-C levels was -2 mg/dL (interquartile range [IQR], -4 to 1 mg/dL) and -4 mg/dL (IQR, -8 to -1 mg/dL; P < .001), respectively.
• Taking PUC values as reference, 22.9% of Martin/Hopkins LDL-C values were more than 5 mg/dL different and 2.6% were more than 10 mg/dL different than PUC levels.
• Due to underestimation by the Friedewald method, these were found to be significantly less than respective proportions with Friedewald estimation (40.1% and 13.3%; P < .001).
• According to findings, the correlation with PUC LDL-C was significantly higher for Martin/Hopkins vs Friedewald (ρ, 0.918 [95% CI 0.916-0.919] vs ρ, 0.867 [0.865-0.869], P < .001).