Review ArticleClinical Review

Hyperlipidemia: Management with Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors

Muhammed Shahreyar, Salem A. Salem, Mannu Nayyar, Lekha K. George, Nadish Garg and Santhosh K.G. Koshy
The Journal of the American Board of Family Medicine July 2018, 31 (4) 628-634; DOI: https://doi.org/10.3122/jabfm.2018.04.170447

References

  1. 1.↵
    1. Catapano AL,
    2. Graham I,
    3. De Backer G,
    4. et al
    . 2016 ESC/EAS guidelines for the management of dyslipidaemias: the Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Atherosclerosis 2016;253:281–344.
    OpenUrlCrossRefPubMed
  2. 2.↵
    1. Baigent C,
    2. Blackwell L,
    3. Emberson J,
    4. et al
    . Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010;376:1670–81.
    OpenUrlCrossRefPubMedWeb of Science
  3. 3.↵
    1. Stancu C,
    2. Sima A
    . Statins: mechanism of action and effects. J Cell Mol Med 2001;5:378–87.
    OpenUrlCrossRefPubMedWeb of Science
  4. 4.↵
    1. Robinson JG
    . Management of familial hypercholesterolemia: a review of the recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Manag Care Pharm 2013;19:139–49.
    OpenUrlPubMed
  5. 5.↵
    1. Stone NJ,
    2. Robinson JG,
    3. Lichtenstein AH,
    4. et al
    . 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2889–934.
    OpenUrlFREE Full Text
  6. 6.↵
    1. Seidah NG,
    2. Awan Z,
    3. Chretien M,
    4. Mbikay M
    . PCSK9: a key modulator of cardiovascular health. Circ Res 2014;114:1022–36.
    OpenUrlAbstract/FREE Full Text
  7. 7.↵
    1. Lagace TA,
    2. Curtis DE,
    3. Garuti R,
    4. et al
    . Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice. J Clin Invest 2006;116:2995–3005.
    OpenUrlCrossRefPubMedWeb of Science
  8. 8.↵
    1. Seidah NG,
    2. Benjannet S,
    3. Wickham L,
    4. et al
    . The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Proc Natl Acad Sci U S A 2003;100:928–33.
    OpenUrlAbstract/FREE Full Text
  9. 9.↵
    1. Abifadel M,
    2. Varret M,
    3. Rabes JP,
    4. et al
    . Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 2003;34:154–6.
    OpenUrlCrossRefPubMedWeb of Science
  10. 10.↵
    1. Cohen JC,
    2. Boerwinkle E,
    3. Mosley TH Jr..,
    4. Hobbs HH
    . Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 2006;354:1264–72.
    OpenUrlCrossRefPubMedWeb of Science
  11. 11.↵
    1. Preiss D,
    2. Mafham M
    . PCSK9 inhibition: the dawn of a new age in cholesterol lowering? Diabetologia 2017;60:381–9.
    OpenUrl
  12. 12.↵
    1. Zhang XL,
    2. Zhu QQ,
    3. Zhu L,
    4. et al
    . Safety and efficacy of anti-PCSK9 antibodies: a meta-analysis of 25 randomized, controlled trials. BMC Med 2015;13:123.
    OpenUrlCrossRefPubMed
  13. 13.↵
    1. Sattar N,
    2. Preiss D,
    3. Robinson JG,
    4. et al
    . Lipid-lowering efficacy of the PCSK9 inhibitor evolocumab (AMG 145) in patients with type 2 diabetes: a meta-analysis of individual patient data. Lancet Diabetes Endocrinol 2016;4:403–10.
    OpenUrl
  14. 14.↵
    1. Raal FJ,
    2. Giugliano RP,
    3. Sabatine MS,
    4. et al
    . Reduction in lipoprotein(a) with PCSK9 monoclonal antibody evolocumab (AMG 145): a pooled analysis of more than 1,300 patients in 4 phase II trials. J Am Coll Cardiol 2014;63:1278–88.
    OpenUrlFREE Full Text
  15. 15.↵
    1. Clarke R,
    2. Peden JF,
    3. Hopewell JC,
    4. et al
    . Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med 2009;361:2518–28.
    OpenUrlCrossRefPubMedWeb of Science
  16. 16.↵
    1. Robinson JG,
    2. Farnier M,
    3. Krempf M,
    4. et al
    . Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med 2015;372:1489–99.
    OpenUrlCrossRefPubMed
  17. 17.↵
    1. Sabatine MS,
    2. Giugliano RP,
    3. Wiviott SD,
    4. et al
    . Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med 2015;372:1500–9.
    OpenUrlCrossRefPubMed
  18. 18.↵
    1. Sabatine MS,
    2. Giugliano RP,
    3. Keech AC,
    4. et al
    . Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017;376:1713–22.
    OpenUrlCrossRefPubMed
  19. 19.↵
    1. Nicholls SJ,
    2. Puri R,
    3. Anderson T,
    4. et al
    . Effect of evolocumab on progression of coronary disease in statin-treated patients: the GLAGOV randomized clinical trial. JAMA 2016;316:2373–84.
    OpenUrl
  20. 20.↵
    1. Schwartz GG,
    2. Bessac L,
    3. Berdan LG,
    4. et al
    . 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;168:682–9.
    OpenUrlCrossRefPubMedWeb of Science
  21. 21.↵
    1. Sabatine MS,
    2. Giugliano RP,
    3. Keech AC,
    4. et al
    . Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017;376:1713–1722.
    OpenUrlCrossRefPubMed
  22. 22.↵
    1. Giugliano RP,
    2. Mach F,
    3. Zavitz K,
    4. et al
    . Design and rationale of the EBBINGHAUS trial: a phase 3, double-blind, placebo-controlled, multicenter study to assess the effect of evolocumab on cognitive function in patients with clinically evident cardiovascular disease and receiving statin background lipid-lowering therapy-A cognitive study of patients enrolled in the FOURIER trial. Clin Cardiol 2017;40:59–65.
    OpenUrl
  23. 23.↵
    National Clinical Guideline Centre. Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. London: National Institute for Health and Clinical Excellence; 2014.
  24. 24.↵
    1. Naci H,
    2. Brugts J,
    3. Ades T
    . Comparative tolerability and harms of individual statins: a study-level network meta-analysis of 246 955 participants from 135 randomized, controlled trials. Circ Cardiovasc Qual Outcomes 2013;6:390–9.
    OpenUrlAbstract/FREE Full Text
  25. 25.↵
    1. Arrieta A,
    2. Page TF,
    3. Veledar E,
    4. Nasir K
    . Economic evaluation of PCSK9 inhibitors in reducing cardiovascular risk from health system and private payer perspectives. PLoS One. 2017;12:e0169761.
    OpenUrl
  26. 26.↵
    1. Raal FJ,
    2. Stein EA,
    3. Dufour R,
    4. et al
    . PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial. Lancet 2015;385:331–40.
    OpenUrlCrossRefPubMed
  27. 27.↵
    1. Mazhar F,
    2. Haider N
    . Proprotein convertase subtilisin/kexin type 9 enzyme inhibitors: An emerging new therapeutic option for the treatment of dyslipidemia. J Pharmacol Pharmacother 2016;7:190–3.
    OpenUrl
  28. 28.↵
    1. Orringer CE,
    2. Jacobson TA,
    3. Saseen JJ,
    4. et al
    . Update on the use of PCSK9 inhibitors in adults: recommendations from an expert panel of the National Lipid Association. J Clin Lipidol 2017;11:880–90.
    OpenUrl
Back to top

In this issue

Print
Download PDF
Article Alerts
Email Article
Citation Tools

Jump to section

Keywords