Effects of Evolocumab on the ApoA1 Remnant Ratio: A Pooled Analysis of Phase 3 Studies

Heidi T May, Joseph B Muhlestein, Yuhui Ma, J Antonio G López, Blai Coll, John Nelson, Heidi T May, Joseph B Muhlestein, Yuhui Ma, J Antonio G López, Blai Coll, John Nelson

Abstract

Introduction: The apolipoprotein A1 (apoA1) remnant ratio has been identified as an independent cardiovascular (CV) risk factor. Higher apoA1 remnant ratios may predict lower CV risk in some patients. This analysis aimed to evaluate the effects of evolocumab on the change from baseline in the apoA1 remnant ratio compared with placebo.

Methods: This pooled post hoc analysis included 2464 patients with mixed dyslipidemia treated with evolocumab 140 mg every 2 weeks (Q2W) or 420 mg once monthly (QM) in three phase 3 evolocumab trials. The apoA1 remnant ratio was calculated by dividing apoA1 by the difference between non-high-density lipoprotein cholesterol (non-HDL-C) and low-density lipoprotein cholesterol (LDL-C). ApoA1 remnant ratio strata were generated using previously published tertile (< 4.7, 4.7-6.8, and > 6.8) and partitioning categories (< 3.6, 3.6-6.0, and > 6.0).

Results: The baseline apoA1 remnant ratio in evolocumab and placebo treatment arms was 7.1 and 7.3, respectively. At week 12, evolocumab 140 mg Q2W and 420 mg QM increased the apoA1 remnant ratio by 25.0% and 33.6%, respectively, versus placebo (p < 0.0001 for both groups). When patients were categorized by week 12 apoA1 remnant ratio thresholds (< 3.6 vs. > 3.6, and < 4.7 vs. > 4.7), those with higher week 12 apoA1 remnant ratios were significantly more likely to have also achieved a target non-HDL-C level of < 100 mg/dl. In the subset of women > 50 years of age, the proportion of patients at apoA1 remnant ratio thresholds < 3.6, 3.6-6.0, and > 6.0 at baseline shifted toward or remained at higher thresholds at week 12.

Conclusions: This post hoc analysis suggests that evolocumab increases the apoA1 remnant ratio.

Funding: Amgen Inc. Plain language summary available for this article.

Keywords: Evolocumab; Mixed dyslipidemia; Non-HDL-C; PCSK9; Remnant lipoprotein; Threshold; VLDL.

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