Effect of Evolocumab on Non-High-Density Lipoprotein Cholesterol, Apolipoprotein B, and Lipoprotein(a): A Pooled Analysis of Phase 2 and Phase 3 Studies

Abstract

Background Dyslipidemia guidelines recommend non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (ApoB) as additional targets of therapy and consider lipoprotein(a) a significant cardiovascular risk marker. The current analysis evaluates the effects of evolocumab on these parameters in various patient populations over time. Methods and Results Data from 7690 patients, 4943 of whom received at least 1 dose of evolocumab, in 15 phase 2 and phase 3 studies with a duration ranging from 12 weeks to 5 years were pooled based on study length, patient population, and ezetimibe or placebo comparator groups. Patients could receive intensive statin therapy but not in the statin intolerance and monotherapy studies. The effects of evolocumab on percent change from baseline for non-HDL-C, ApoB, and lipoprotein(a) and achievement of treatment goals for non-HDL-C and ApoB were examined. Compared with placebo, evolocumab at both approved dosing regimens substantially reduced mean non-HDL-C (Q2W dose: -49% to -56%, monthly dose: -48% to -52%), mean ApoB (Q2W dose: -46% to -52%, monthly dose: -40% to -48%), and median lipoprotein(a) (Q2W dose: -22% to -38%, monthly dose: -20% to -33%) at 12 weeks. Effects on all 3 parameters persisted over 5 years. Lipid-lowering effects were consistent among the patient populations examined (hypercholesterolemia/mixed dyslipidemia, statin intolerance, heterozygous familial hypercholesterolemia, and type 2 diabetes mellitus). Conclusions In this pooled analysis, evolocumab substantially reduced non-HDL-C, ApoB, and lipoprotein(a) compared with placebo. The effect was consistent and maintained in various patient populations over 5 years.

Keywords: apolipoprotein; lipids and lipoproteins; low‐density lipoprotein cholesterol.

Figures

Figure 1

Percent change in non‐HDL‐C, ApoB, Lp(a), LDL‐C, VLDL‐C, and TG from baseline. Forest plots highlight the percent change in non‐HDL‐C, ApoB, Lp(a), VLDL‐C, and TG from baseline with evolocumab, placebo, and ezetimibe for all 12‐week studies by patient population. Individual patient data were pooled across studies within each patient population. The dots represent mean values, and the error bars depict the 95% CIs. ApoB indicates apolipoprotein B; HeFH, heterozygous familial hypercholesterolemia; LDL‐C, low‐density lipoprotein cholesterol; Lp(a), lipoprotein(a); non‐HDL‐C, non‐high‐density lipoprotein cholesterol; N, number of patients within each group with a nonmissing percent change from baseline at week 12; Q2W, every‐2‐week, QM, once monthly; TG, triglycerides; VLDL‐C, very‐low‐density lipoprotein cholesterol.

Figure 2

Percent achievement in placebo or ezetimibe‐controlled phase 2 and phase 3 evolocumab studies of (A) Non‐HDL‐C <100 mg/dL (2.6 mmol/L) and (B) ApoB <80 mg/dL. The percentages of patients who achieved non‐HDL‐C <100 mg/dL (A) and ApoB <80 mg/dL (B) with evolocumab, ezetimibe, or placebo are depicted in this plot for all studies with a placebo or ezetimibe comparator. Results are shown separately for each patient population examined (hypercholesterolemia/mixed dyslipidemia, type 2 diabetes mellitus, heterozygous FH, and statin intolerance), all 12 weeks in duration, as well as for the 1‐year study (DESCARTES). ApoB indicates apolipoprotein B; FH, familial hypercholesterolemia; non‐HDL‐C, non‐high‐density lipoprotein cholesterol. *Evolocumab‐treated patients with ezetimibe comparator arm; †Evolocumab‐treated patients with placebo comparator arm.