Dataset Information

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.

SUBMITTER: Toth PP

PROVIDER: S-EPMC7335559 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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

Toth Peter P PP Jones Steven R SR Monsalvo Maria Laura ML Elliott-Davey Mary M López J Antonio G JAG Banach Maciej M

Journal of the American Heart Association 20200302 5

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 rang ...[more]

PMID: 32114889

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Project description:ImportanceLittle is known about the heterogeneity in low-density lipoprotein cholesterol levels (LDL-C) lowering with proprotein convertase subtilisin kexin 9 (PCSK9) inhibitor medications.ObjectiveTo evaluate the interindividual variability in LDL-C reduction with the PCSK9 inhibitor drug evolocumab.Design, setting, and participantsWe examined the percentage change in LDL-C levels from baseline in the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial, a placebo-controlled randomized clinical trial of the PCSK9 inhibitor evolocumab in patients with stable atherosclerotic cardiovascular disease who were taking statin medications. Patients in either treatment arm who had high baseline LDL-C variability during screening and either did not receive the study drug, altered their background lipid-lowering therapy regimen, or had no LDL-C level sample in week 4 were excluded from the primary analysis. Analyses in the patients were stratified by treatment arm. Data was collected from 2013 to 2016, and data were analyzed from January 2018 to November 2018.Main outcomes and measuresInterindividual variation in percent reduction in LDL-C with evolocumab.ResultsThere were 27 564 individuals in the cohort; after exclusions for baseline variability (n = 3524) or alterations in background lipid therapy and other causes (n = 2272), 21 768 patients remained. At week 4, the median percent reduction in LDL-C levels from baseline was 66% (interquartile range, 54%-76%; median [interquartile range] baseline value, 90 [79-105] mg/dL; postchange value, 31 [21-44] mg/dL) with evolocumab. During the first year, a total of 10 325 of 10902 patients in the evolocumab group (94.7%) had a reduction 50% or greater in LDL-C levels, 10 669 of 10 902 (97.9%) had a reduction 30% or more, and 10 849 of 10 902 (99.5%) had any reduction in LDL-C levels. Fifty-three patients (0.5%) had no apparent reduction in LDL-C levels. In the placebo arm, the median LDL-C reduction was 4% (interquartile range, 6% increase to 13% reduction; baseline median [IQR] value, 90 [79-106] mg/dL; postchange value, 87 [74-103] mg/dL) at 4 weeks. Waterfall plots showed notable variability in the top and bottom 5% of patients for both evolocumab and placebo groups, with large changes in LDL-C levels in the placebo group (increases of ≥25%, 531 patients [4.9%]; decreases of ≥25%, 985 patients [9.1%]). At 4 weeks, the placebo-adjusted reductions in LDL-C levels with evolocumab were 50% or greater in 9839 of 10 866 patients (90.5%) and 30% or greater in 10 846 of 10 866 patients (99.8%). Results were consistent across clinically relevant subgroups.Conclusions and relevanceThere appears to be a highly consistent robust reduction in LDL-C levels with evolocumab use.Trial registrationClinicalTrials.gov identifier: NCT01764633.

Dataset Information

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

Publications

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

Similar Datasets

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