LDL-C calculated by Friedewald, Martin-Hopkins, or NIH Equation 2 versus beta-quantification: pooled alirocumab trials

J Lipid Res. 2021 Nov 10;100148. doi: 10.1016/j.jlr.2021.100148. Online ahead of print.


Accurate assessment of LDL-C levels is important, as they are often used for treatment recommendations. For many years, plasma LDL-C levels were calculated using the Friedewald equation, but there are limitations to this method compared with direct measurement via beta-quantification (BQ). Here we assessed differences between the Friedewald, Martin-Hopkins, and NIH Equation 2 methods of calculating LDL-C and the "gold standard" BQ method using pooled Phase 3 data with alirocumab (a PCSK9 inhibitor). All randomized patients were included irrespective of treatment arm (n = 6122). We compared pairs of LDL-C values (n=17,077) determined by each equation and BQ. We found that BQ-derived LDL-C values ranged from 1 to 397 mg/dL (mean 90.68 mg/dL). There were strong correlations between Friedewald-, Martin-Hopkins-, and NIH Equation 2-calculated LDL-C with BQ-determined LDL-C values (Pearson's correlation coefficient = 0.985, 0.981, and 0.985, respectively). Importantly, for BQ-derived LDL-C values ≥70 mg/dL, only 3.2%, 1.4%, and 1.8% of Friedewald-, Martin-Hopkins-, and NIH Equation 2-calculated values were <70 mg/dL, respectively. When TG levels were <150 mg/dL, differences between calculated and BQ-derived LDL-C values were minimal, regardless of LDL-C level (<40, <55 or <70 mg/dL). However, when TG levels were >150 mg/dL, NIH Equation 2 provided greater accuracy versus Friedewald or Martin-Hopkins. When TG were >250 mg/dL, inaccuracies were seen with all three methods, although NIH Equation 2 remained the most accurate. In conclusion, LDL-C calculated by any of the three methods can guide treatment decisions in the large majority of patients, including those treated with PCSK9 inhibitors.

Keywords: Alirocumab; Friedewald; LDL; Martin-Hopkins; NIH Equation 2; PCSK9; beta-quantification; calculated LDL-C; cholesterol; drug therapy/hypolipidemic drugs.