Relationship between low-density lipoprotein cholesterol, free proprotein convertase subtilisin/kexin type 9, and alirocumab levels after different lipid-lowering strategies

Journal of the American Heart Association

Volumn 5, Issue 6, 2016, Pages

  Rey, Jacques ^a   Poitiers, Franck ^a   Paehler, Tobias ^b   Brunet, Aurélie ^a   DiCioccio, A Thomas ^c   Cannon, Christopher P ^d   Surks, Howard K ^a   Pinquier, Jean Louis ^a   Hanotin, Corinne ^a   Sasiela, William J ^c  

^a SANOFI   (France)

^b Sanofi   (Germany)

^c REGENERON PHARMACEUTICALS INC   (United States)

^d HARVARD CLINICAL RESEARCH INSTITUTE   (United States)

Author keywords

Cholesterol; Hypercholesterolemia; Lipids; Pharmacokinetics

Indexed keywords

ALIROCUMAB; EZETIMIBE; FENOFIBRATE; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PLACEBO; PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9; SERINE PROTEINASE; UNCLASSIFIED DRUG; ANTILIPEMIC AGENT; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; HYPOCHOLESTEROLEMIC AGENT; MONOCLONAL ANTIBODY; PCSK9 PROTEIN, HUMAN; PROPROTEIN CONVERTASE 9;

ABDOMINAL PAIN; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG CLEARANCE; DRUG EFFECT; DRUG RESPONSE; DRUG SAFETY; FEMALE; FLU LIKE SYNDROME; HEADACHE; HUMAN; HYPERCHOLESTEROLEMIA; INFLUENZA; MALE; MAXIMUM PLASMA CONCENTRATION; MULTICENTER STUDY; PHARMACODYNAMICS; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RHINOPHARYNGITIS; TREATMENT OUTCOME; VIRAL GASTROENTERITIS; ADOLESCENT; ADULT; AGED; BLOOD; CLINICAL TRIAL; COMBINATION DRUG THERAPY; DOUBLE BLIND PROCEDURE; DRUG EFFECTS; METABOLISM; MIDDLE AGED; ORAL DRUG ADMINISTRATION; YOUNG ADULT;

ADMINISTRATION, ORAL; ADOLESCENT; ADULT; AGED; ANTIBODIES, MONOCLONAL; ANTICHOLESTEREMIC AGENTS; CHOLESTEROL, LDL; DOUBLE-BLIND METHOD; DRUG THERAPY, COMBINATION; EZETIMIBE; FEMALE; FENOFIBRATE; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; HYPERCHOLESTEROLEMIA; HYPOLIPIDEMIC AGENTS; MALE; MIDDLE AGED; PROPROTEIN CONVERTASE 9; YOUNG ADULT;

EID: 84996467559     PISSN: None     EISSN: 20479980     Source Type: Journal    
DOI: 10.1161/JAHA.116.003323     Document Type: Article

References (18)

1. Seidah NG, Awan Z, Chretien M, Mbikay M. PCSK9: a key modulator of cardiovascular health. Circ Res. 2014;114:1022-1036.
2. Guo YL, Zhang W, Li JJ. PCSK9 and lipid lowering drugs. Clin Chim Acta. 2014;437:66-71.
3. Cannon CP, Cariou B, Blom D, McKenney JM, Lorenzato C, Pordy R, Chaudhari U, Colhoun HM; ODYSSEY COMBO II Investigators. 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;36:1186-1194.
4. McKenney JM, Koren MJ, Kereiakes DJ, Hanotin C, Ferrand AC, Stein EA. 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;59:2344-2353.
5. Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M, Stroes ES, Langslet G, Raal FJ, El Shahawy M, Koren MJ, Lepor NE, Lorenzato C, Pordy R, Chaudhari U, Kastelein JJ; Investigators OLT. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372:1489-1499.
6. Stein EA, Gipe D, Bergeron J, Gaudet D, Weiss R, Dufour R, Wu R, Pordy 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 controlled trial. Lancet. 2012;380:29-36.
7. Stein EA, Mellis S, Yancopoulos GD, Stahl N, Logan D, Smith WB, Lisbon E, Gutierrez M, Webb C, Wu R, Du Y, Kranz T, Gasparino E, Swergold GD. Effect of a monoclonal antibody to PCSK9 on LDL cholesterol. N Engl J Med. 2012;366:1108-1118.
8. Merck Sharp & Dohme Limited. Ezetrol 10 mg tablets. Available at: https://www.medicines.org.uk/emc/medicine/12091/SPC/Ezetrol+10mg+Tablets/. Accessed January 4, 2016.
9. Genus Pharmaceuticals. Fenofibrate 160 mg tablets. Available at: https://www.medicines.org.uk/emc/medicine/28612. Accessed January 4, 2016.
10. Ason B, Tep S, Davis HR Jr, Xu Y, TetzloffG, Galinski B, Soriano F, Dubinina N, Zhu L, Stefanni A, Wong KK, Tadin-Strapps M, Bartz SR, Hubbard B, Ranalletta M, Sachs AB, Flanagan WM, Strack A, Kuklin NA. Improved efficacy for ezetimibe and rosuvastatin by attenuating the induction of PCSK9. J Lipid Res. 2011;52:679-687.
11. Zhang Y, Liu J, Li S, Xu RX, Sun J, Li JJ. Impact of currently prescribed lipidlowering drugs on plasma PCSK9 concentration: single or in combination study in rats. Lipids Health Dis. 2014;13:35.
12. Berthold HK, Seidah NG, Benjannet S, Gouni-Berthold I. Evidence from a randomized trial that simvastatin, but not ezetimibe, upregulates circulating PCSK9 levels. PLoS One. 2013;8:e60095.
13. Sahebkar A. Circulating levels of proprotein convertase subtilisin kexin type 9 are elevated by fibrate therapy: a systematic review and meta-analysis of clinical trials. Cardiol Rev. 2014;22:306-312.
14. Gustavson LE, Schweitzer SM, Burt DA, Achari R, Rieser MJ, Edeki T, Chira T, Yannicelli HD, Kelly MT. Evaluation of the potential for pharmacokinetic interaction between fenofibrate and ezetimibe: a phase I, open-label, multipledose, three-period crossover study in healthy subjects. Clin Ther. 2006;28:373-387.
15. Khera AV, Qamar A, Reilly MP, Dunbar RL, Rader DJ. Effects of niacin, statin, and fenofibrate on circulating proprotein convertase subtilisin/kexin type 9 levels in patients with dyslipidemia. Am J Cardiol. 2015;115:178-182.
16. Chaparro-Riggers J, Liang H, DeVay RM, Bai L, Sutton JE, Chen W, Geng T, Lindquist K, Casas MG, Boustany LM, Brown CL, Chabot J, Gomes B, Garzone P, Rossi A, Strop P, Shelton D, Pons J, Rajpal A. Increasing serum half-life and extending cholesterol lowering in vivo by engineering antibody with pHsensitive binding to PCSK9. J Biol Chem. 2012;287:11090-11097.
17. Schwartz GG, Bessac L, Berdan LG, Bhatt DL, Bittner V, Diaz R, Goodman SG, Hanotin C, Harrington RA, Jukema JW, Mahaffey KW, Moryusef A, Pordy R, Roe MT, Rorick T, Sasiela WJ, Shirodaria C, Szarek M, Tamby JF, Tricoci P, White H, Zeiher A, Steg PG. Effect of alirocumab, a monoclonal antibody to PCSK9, on long-term cardiovascular outcomes following acute coronary syndromes: rationale and design of the ODYSSEY outcomes trial. Am Heart J. 2014;168:682-689.
18. Bruckert E, Hayem G, Dejager S, Yau C, Begaud B. Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients-the PRIMO study. Cardiovasc Drugs Ther. 2005;19:403-414.