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

•Remnant lipoprotein cholesterol measurement methods showed little agreement. •Correlations between the measurement methods were generally moderate to strong. •Ezetimibe/statin showed greater remnant lipoprotein cholesterol reduction vs statin. •There is a need to standardize remnant lipoprotein cholesterol measurement methods. 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. 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 10/20/40/80 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. 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.