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

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. All randomized patients were included irrespective of the treatment arm (n = 6,122). 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-calculated, Martin-Hopkins-calculated, 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-calculated, Martin-Hopkins-calculated, and NIH equation 2-calculated values were <70 mg/dl, respectively. When triglyceride (TG) levels were <150 mg/dl, differences between calculated and BQ-derived LDL-C values were minimal, regardless of the LDL-C level (<40, <55, or <70 mg/dl). However, when TG levels were >150 mg/dl, NIH equation 2 provided greater accuracy than Friedewald or Martin-Hopkins. When TGs 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 for most patients, including those treated with proprotein convertase subtilisin/kexin type 9 inhibitors.
Competing Interests: Conflict of interest H. N. G. has received research grants from Sanofi, Regeneron Pharmaceuticals, Inc., Pfizer, AstraZeneca, and Amgen and modest consultant/advisory board fees from Amarin, Amgen, AstraZeneca, Ionis, Janssen, Kowa, Merck, Novartis, Sanofi, Regeneron Pharmaceuticals, Inc., and Pfizer Inc. R. S. R. has received research grants through his institution from Amgen, Arrowhead, Novartis, and Regeneron Pharmaceuticals, Inc. G. K. H. is a holder of a Vidi Grant (016.156.445) from the Netherlands Organisation for Scientific Research (NWO) and Klinkerpad, has received research support through his institution from Aegerion, Amgen, and Sanofi and speaker fees from Amgen, Aegerion, Sanofi, Regeneron Pharmaceuticals, Inc., and Pfizer. C. P. C. has received research grants from Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Janssen, Merck, and Pfizer and consulting fees from Aegerion, Alnylam, Amarin, Amgen, Applied Therapeutics, Ascendia, Boehringer Ingelheim, Bristol-Myers Squibb, Corvidia, HLS Therapeutics, Innovent, Janssen, Kowa, Merck, Pfizer, and Sanofi. R. S. R. serves on advisory boards from Amgen, Amyrt, C5, CVS Caremark, and Regeneron Pharmaceuticals, Inc., receives honoraria from Amgen, Kowa, and Regeneron Pharmaceuticals, Inc., receives royalties from UpToDate, and has stock ownership in MediMergent. G. K. H. has served as a consultant for Amgen, Aegerion, Sanofi, Regeneron Pharmaceuticals, Inc., and Pfizer and has been employed part-time by Novo Nordisk AS and Copenhagen, Denmark, since April 2019. A. L. is an employee of and stockholder in Sanofi. R. S. is an employee of and stockholder in Regeneron Pharmaceuticals, Inc. Y. P. is employed by a company that is contracted to Sanofi. All other authors declare that they have no conflicts of interest with the contents of this article.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)