Effect of Alirocumab on Specific Lipoprotein Non-high-density Lipoprotein Cholesterol and Subfractions As Measured by the Vertical Auto Profile Method: Analysis of 3 Randomized Trials Versus Placebo

Overview

Journal Lipids Health Dis

Publisher Biomed Central

Specialties Biochemistry
Endocrinology

Date 2016 Feb 14

PMID 26872608

Citations 14

Authors

Peter P Toth

Sara C Hamon

Steven R Jones

Seth S Martin

Parag H Joshi

Krishnaji R Kulkarni

Poulabi Banerjee

Corinne Hanotin

Eli M Roth

James M McKenney

Affiliations

Soon will be listed here.

Abstract

Background: The effect of alirocumab on potentially atherogenic lipoprotein subfractions was assessed in a post hoc analysis using the vertical auto profile (VAP) method.

Methods: Patients from three Phase II studies with low-density lipoprotein cholesterol (LDL-C) ≥ 2.59 mmol/L (100 mg/dL) at baseline on stable statin therapy were randomised to receive subcutaneous alirocumab 50-150 mg every 2 weeks (Q2W) or 150-300 mg every 4 weeks (according to study) or placebo for 8-12 weeks. Samples from patients treated with alirocumab 150 mg Q2W (n = 74; dose common to all three trials) or placebo (n = 71) were analysed by VAP. Percent change in lipoprotein subfractions with alirocumab vs. placebo was analysed at Weeks 6, 8 or 12 using analysis of covariance.

Results: Alirocumab significantly reduced LDL-C and the cholesterol content of subfractions LDL1, LDL2 and LDL3+4. Significant reductions were also observed in triglycerides, apolipoproteins CII and CIII and the cholesterol content of very low-density, intermediate-density, and remnant lipoproteins.

Conclusion: Alirocumab achieved reductions across a spectrum of atherogenic lipoproteins in patients receiving background statin therapy.

Trial Registration: Clinicaltrials.gov identifiers: NCT01288443, NCT01288469, NCT01266876.

Citing Articles

Remnant Cholesterol and Residual Risk of Atherosclerotic Cardiovascular Disease.

Li X, Li Z, Wu N Rev Cardiovasc Med. 2025; 26(2):25985.

PMID: 40026498 PMC: 11868899. DOI: 10.31083/RCM25985.

Efficacy and safety of PCSK9 inhibitors, potent statins, and their combinations for reducing low-density lipoprotein cholesterol in hyperlipidemia patients: a systematic network meta-analysis.

Jiang Y, Wang Y, Ma S, Qian L, Jing Y, Chen X Front Cardiovasc Med. 2025; 11:1415668.

PMID: 39975967 PMC: 11836037. DOI: 10.3389/fcvm.2024.1415668.

Efficacy and Safety of Evolocumab and Alirocumab as PCSK9 Inhibitors in Pediatric Patients with Familial Hypercholesterolemia: A Systematic Review and Meta-Analysis.

Xiao G, Gao S, Xie Y, Wang Z, Shu M Medicina (Kaunas). 2024; 60(10).

PMID: 39459433 PMC: 11509226. DOI: 10.3390/medicina60101646.

A significant presence in atherosclerotic cardiovascular disease: Remnant cholesterol: A review.

Wang L, Zhang Q, Wu Z, Huang X Medicine (Baltimore). 2024; 103(27):e38754.

PMID: 38968507 PMC: 11224847. DOI: 10.1097/MD.0000000000038754.

The residual risk of inflammation and remnant cholesterol in acute coronary syndrome patients on statin treatment undergoing percutaneous coronary intervention.

Liao J, Qiu M, Su X, Qi Z, Xu Y, Liu H Lipids Health Dis. 2024; 23(1):172.

PMID: 38849939 PMC: 11157837. DOI: 10.1186/s12944-024-02156-3.

References

Kei A, Filippatos T, Tsimihodimos V, Elisaf M . A review of the role of apolipoprotein C-II in lipoprotein metabolism and cardiovascular disease. Metabolism. 2012; 61(7):906-21. DOI: 10.1016/j.metabol.2011.12.002. View

Kulkarni K, Garber D, Marcovina S, Segrest J . Quantification of cholesterol in all lipoprotein classes by the VAP-II method. J Lipid Res. 1994; 35(1):159-68. View

Bays H, Jones P, Brown W, Jacobson T . National Lipid Association Annual Summary of Clinical Lipidology 2015. J Clin Lipidol. 2014; 8(6 Suppl):S1-36. DOI: 10.1016/j.jacl.2014.10.002. View

Taskinen M, Boren J . New insights into the pathophysiology of dyslipidemia in type 2 diabetes. Atherosclerosis. 2015; 239(2):483-95. DOI: 10.1016/j.atherosclerosis.2015.01.039. View

Robinson J, Farnier M, Krempf M, Bergeron J, Luc G, Averna M . Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015; 372(16):1489-99. DOI: 10.1056/NEJMoa1501031. View

Cannon C, Cariou B, Blom D, McKenney J, Lorenzato C, Pordy R . Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins: the ODYSSEY COMBO II randomized controlled trial. Eur Heart J. 2015; 36(19):1186-94. PMC: 4430683. DOI: 10.1093/eurheartj/ehv028. View

Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F . Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004; 364(9438):937-52. DOI: 10.1016/S0140-6736(04)17018-9. View

Jong M, Rensen P, Dahlmans V, van der Boom H, Van Berkel T, Havekes L . Apolipoprotein C-III deficiency accelerates triglyceride hydrolysis by lipoprotein lipase in wild-type and apoE knockout mice. J Lipid Res. 2001; 42(10):1578-85. View

Rader D, Hoeg J, BREWER Jr H . Quantitation of plasma apolipoproteins in the primary and secondary prevention of coronary artery disease. Ann Intern Med. 1994; 120(12):1012-25. DOI: 10.7326/0003-4819-120-12-199406150-00008. View

10.

OKeefe Jr J, Captain B, Jones P, Harris W . Atorvastatin reduces remnant lipoproteins and small, dense low-density lipoproteins regardless of the baseline lipid pattern. Prev Cardiol. 2004; 7(4):154-60. DOI: 10.1111/j.1520-037x.2004.03594.x. View

11.

Kulkarni K . Cholesterol profile measurement by vertical auto profile method. Clin Lab Med. 2006; 26(4):787-802. DOI: 10.1016/j.cll.2006.07.004. View

12.

MacArthur J, Bishop J, Stanford K, Wang L, Bensadoun A, Witztum J . Liver heparan sulfate proteoglycans mediate clearance of triglyceride-rich lipoproteins independently of LDL receptor family members. J Clin Invest. 2007; 117(1):153-64. PMC: 1716206. DOI: 10.1172/JCI29154. View

13.

Jones C, Garuti R, Michaely P, Li W, Maeda N, Cohen J . Disruption of LDL but not VLDL clearance in autosomal recessive hypercholesterolemia. J Clin Invest. 2007; 117(1):165-74. PMC: 1716209. DOI: 10.1172/JCI29415. View

14.

Lillis A, Van Duyn L, Murphy-Ullrich J, Strickland D . LDL receptor-related protein 1: unique tissue-specific functions revealed by selective gene knockout studies. Physiol Rev. 2008; 88(3):887-918. PMC: 2744109. DOI: 10.1152/physrev.00033.2007. View

15.

Krauss R . Lipoprotein subfractions and cardiovascular disease risk. Curr Opin Lipidol. 2010; 21(4):305-11. DOI: 10.1097/MOL.0b013e32833b7756. View

16.

Bays H, Conard S, Leiter L, Bird S, Jensen E, Hanson M . Are post-treatment low-density lipoprotein subclass pattern analyses potentially misleading?. Lipids Health Dis. 2010; 9:136. PMC: 3012666. DOI: 10.1186/1476-511X-9-136. View

17.

Reiner Z, Catapano A, De Backer G, Graham I, Taskinen M, Wiklund O . ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J. 2011; 32(14):1769-818. DOI: 10.1093/eurheartj/ehr158. View

18.

McKenney J, Koren M, Kereiakes D, Hanotin C, Ferrand A, Stein E . Safety and efficacy of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease, SAR236553/REGN727, in patients with primary hypercholesterolemia receiving ongoing stable atorvastatin therapy. J Am Coll Cardiol. 2012; 59(25):2344-53. DOI: 10.1016/j.jacc.2012.03.007. View

19.

Stein E, Gipe D, Bergeron J, Gaudet D, Weiss R, Dufour R . Effect of a monoclonal antibody to PCSK9, REGN727/SAR236553, to reduce low-density lipoprotein cholesterol in patients with heterozygous familial hypercholesterolaemia on stable statin dose with or without ezetimibe therapy: a phase 2 randomised.... Lancet. 2012; 380(9836):29-36. DOI: 10.1016/S0140-6736(12)60771-5. View

20.

Roth E, McKenney J, Hanotin C, Asset G, Stein E . Atorvastatin with or without an antibody to PCSK9 in primary hypercholesterolemia. N Engl J Med. 2012; 367(20):1891-900. DOI: 10.1056/NEJMoa1201832. View