Comparing remnant lipoprotein cholesterol measurement methods to evaluate efficacy of ezetimibe/statin vs statin therapy

Peter P. Toth, Harold E. Bays, W. Virgil Brown, Alberico L. Catapano, Michael H. Davidson, Michel Farnier, Joanne E. Tomassini, Erin Jensen, Adam B. Polis, Andrew M. Tershakovec

Research output: Contribution to journalArticle

Abstract

Background: Elevated remnant lipoprotein cholesterol (RLP-C) levels increase cardiovascular disease risk. However, RLP-C measurement methods are not standardized, leading to variations across studies. Objective: To evaluate the effect of ezetimibe (Eze) + statins vs statin monotherapy on RLP-C using immunoseparation (IM), vertical auto profile (VAP) ultracentrifugation, and calculated RLP-C measurement methods. Methods: This post hoc analysis evaluated data pooled from 3 first-line (all-statin [simvastatin 10/20/40/80 mg] vs Eze + statin [Eze 10 mg + simvastatin]) and 2 second-line (statin [atorvastatin uptitrated to 40/80 mg] vs statin + Eze [atorvastatin 20/40 mg + Eze 10 mg]) studies. Similarity of RLP-C methods was evaluated using Pearson correlation coefficients and Bland-Altman plots. RLP-C changes and percent changes from baseline were measured by all 3 methods in first-line and VAP and calculated methods in second-line studies. Results: Correlations between methods were generally moderate to strong for RLP-C levels, changes, and percent changes across treatment groups (r = 0.29–0.79) but with little evidence of agreement by Bland-Altman plots. Baseline RLP-C levels for Eze + statin vs all-statin groups were lower by IM (14.0 vs 14.0) compared with VAP (36.9 vs 35.9) and calculated (32.8 vs 33.3) methods. RLP-C changes (mg/dL) and percent changes from baseline were significantly greater (P < .01) with Eze + statins vs statins by VAP, calculated, and IM methods (between-treatment differences: −5.0 and −12.0, −2.0 and −5.4, and −1.5 and −12.1, respectively) in first-line, and VAP and calculated methods (between-treatment differences: −5.0 and −19.9 and −2.0 and −7.3) in second-line studies. Conclusion: Although the 3 methods showed little agreement, each supported Eze + statins for achieving greater RLP-C reductions vs statin monotherapy; variability of results reinforces urgent need to standardize RLP-C measurements.

Original languageEnglish
Pages (from-to)997-1007.e8
JournalJournal of Clinical Lipidology
Volume13
Issue number6
DOIs
Publication statusPublished - Nov 1 2019

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Keywords

  • Ezetimibe
  • Immunoseparation
  • Remnant lipoprotein cholesterol
  • Statin
  • Vertical auto profile ultracentrifugation

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics
  • Cardiology and Cardiovascular Medicine

Cite this

Toth, P. P., Bays, H. E., Brown, W. V., Catapano, A. L., Davidson, M. H., Farnier, M., Tomassini, J. E., Jensen, E., Polis, A. B., & Tershakovec, A. M. (2019). Comparing remnant lipoprotein cholesterol measurement methods to evaluate efficacy of ezetimibe/statin vs statin therapy. Journal of Clinical Lipidology, 13(6), 997-1007.e8. https://doi.org/10.1016/j.jacl.2019.09.001