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

Abstract

Elevated remnant lipoprotein cholesterol (RLP-C) levels increase cardiovascular disease risk. However, RLP-C measurement methods are not standardized, leading to variations across studies. 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. This post hoc analysis evaluated data pooled from 3 first-line (all-statin [simvastatin 10/20/40/80mg] vs Eze+statin [Eze 10mg+simvastatin]) and 2 second-line (statin [atorvastatin uptitrated to 40/80mg] vs statin+Eze [atorvastatin 20/40mg+Eze 10mg]) 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. 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. 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.