1887
Volume 2015, Issue 2
  • ISSN: 2305-7823
  • EISSN:

Abstract

Proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors have emerged as a novel treatment option in patients with hypercholesterolemia. Evolocumab and alirocumab have achieved consistent and significant (around 60%) reduction in low-density lipoprotein cholesterol (LDL-C) levels when added to statin therapy in short term studies. The Open-Label Study of Long-term Evaluation Against LDL-C (OSLER), and The Long-term Safety and Tolerability of Alirocumab in High Cardiovascular Risk Patients with Hypercholesterolemia Not Adequately Controlled with Their Lipid Modifying Therapy (ODYSSEY LONG TERM) studies are two phase 3, multicentre, randomized, placebo controlled studies that were conducted to evaluate the long term efficacy and safety of evolocumab and alirocumab respectively in reducing lipids and cardiovascular (CV) events. Both studies demonstrated additional 48–53% reduction of CV events when added to statin therapy. Most adverse events occurred with similar frequency in the two groups; however the rate of neurocognitive adverse events was higher with evolocumab and alirocumab than with placebo. These data provide strong support for the notion that lower LDL-C goal is better, and may confirm the role of PCSK9 inhibitors as a new frontier in lipid management. The results of larger long-term outcome studies are still awaited.

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2015-06-26
2020-09-22
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References

  1. Hassan M, Yacoub M. GAUSS-2, RUTHERFORD-2, LAPLACE-2, DESCARTES, and TESLA Part B: PCSK9 inhibitors gain momentum. Glob. Cardiol. Sci. Pract. 2014; 4::3606.
    [Google Scholar]
  2. Elguindy A, Yacoub MH. The discovery of PCSK9 inhibitors: A tale of creativity and multifaceted translational research. Glob. Cardiol. Sci. Pract. 2013; 4::343347.
    [Google Scholar]
  3. Stroes E, Colquhoun D, Sullivan D, Civeira F, Rosenson RS, Watts GF, Bruckert E, Cho L, Dent R, Knusel B, Xue A, Scott R, Wasserman SM, Rocco M. Anti-PCSK9 Antibody Effectively Lowers Cholesterol in Patients With Statin Intolerance. J Am Coll Cardiol. 2014; 63:23:25412548.
    [Google Scholar]
  4. Raal FJ, Stein EA, Dufour R, Turner T, Civeira F, Burgess L, Langslet G, Scott R, Olsson AG, Sullivan D, Hovingh GK, Cariou B, Gouni-Berthold I, Somaratne R, Bridges I, Scott R, Wasserman SM, Gaudet D. PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial. Lancet. 2015; 385:9965:331340.
    [Google Scholar]
  5. Raal FJ, Honarpour N, Blom DJ, Hovingh GK, Xu F, Scott R, Wasserman SM, Stein EA. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial. Lancet. 2015; 385:9965:341350.
    [Google Scholar]
  6. Robinson JG, Nedergaard BS, Rogers WJ, Fialkow J, Neutel JM, Ramstad D, Somaratne R, Legg JC, Nelson P, Scott R, Wasserman SM, Weiss R. Effect of Evolocumab or Ezetimibe Added to Moderate- or High-Intensity Statin Therapy on LDL-C Lowering in Patients With Hypercholesterolemia The LAPLACE-2 Randomized Clinical Trial. JAMA. 2014; 311:18:18701882.
    [Google Scholar]
  7. Lillestol MJ, Toth PD, Burgess L, Ceska R, Roth E, Koren MJ, Ballantyne CM, Monsalvo ML, Tsirtsonis K, Kim JB, Scott R, Wasserman SM, Stein EA. A 52-Week. Placebo-Controlled Trial of Evolocumab in Hyperlipidemia. NEJM. 2014; 370:19:18091819.
    [Google Scholar]
  8. McKenney JM, Koren MJ, Kereiakes DJ, Hanotin C, Ferrand A-C, 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; 59:25:23442353.
    [Google Scholar]
  9. Roth EM, McKenney JM, Hanotin C, Asset G, Stein EA. Atorvastatin with or without an antibody to PCSK9 in primary hypercholesterolemia. N. Engl. J. Med. 2012; 367:20:18911900.
    [Google Scholar]
  10. 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 controlle. Lancet. 2012; 380:9836:2936.
    [Google Scholar]
  11. Sabatine MS, Giugliano RP, Wiviott SD, Raal FJ, Blom DJ, Robinson J, Ballantyne CM, Somaratne R, Legg J, Wasserman SM, Scott R, Koren MJ, Stein EA. Efficacy and Safety of Evolocumab in Reducing Lipids and Cardiovascular Events. N. Engl. J. Med. 2015;, doi:10.1056/NEJMoa1500858.
    [Google Scholar]
  12. Gencer B, Mach F. Sweetless'n low LDL-C targets for PCSK9 treatment. Eur. Heart J. 2015;, doi:10.1093/eurheartj/ehv056.
    [Google Scholar]
  13. Dadu RT, Ballantyne CM. Lipid lowering with PCSK9 inhibitors. Nat. Rev. Cardiol. 2014; 11:10:563575.
    [Google Scholar]
  14. Postmus I, Trompet S, de Craen AJ, Buckley BM, Ford I, Stott DJ, Sattar N, Slagboom PE, Westendorp RG, Jukema JW. PCSK9 SNP  rs11591147 is associated with low cholesterol levels but not with cognitive performance or noncardiovascular clinical events in an elderly population. J. Lipid Res. 2013; 54:2:561566.
    [Google Scholar]
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