Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors
Authors:
Ján Murín
Authors place of work:
I. interná klinika LF UK a UN Bratislava, nemocnica Staré mesto
Published in the journal:
AtheroRev 2016; 1(3): 151-154
Category:
Reviews
Summary
Cardiovascular diseases contribute in Slovakia with 53 % to all-cause mortality. These diseases have usually an atherogenic background and the development of these diseases is impossible without an increase in serum LDL-cholesterol. For prevention and treatment of these diseases we use a change of life style and statins, but now a new group of drug will enter this arena – PCSK9 inhibitors. Author presents essential data about mechanisms of effects of these new drugs, about short history of these drugs development and presents important clinical studies with these drugs. He tries to focus on patients who will benefit mostly from this treatment.
Key words:
atherosclerosis – cardiovascular diseases – LDL-cholesterol – PCSK9 inhibitors
Zdroje
1. Agarwal SK, Avery CL, Ballantyne CM et al. Sources of variability in measurements of cardiac troponin T in a community-based sample: the atherosclerosis risk in communities study. Clin Chem 2011; 57(6): 891–897.Dostupné z DOI: <http://dx.doi.org/10.1373/clinchem.2010.159350>.
2. Boekholdt SM, Arsenault BJ, Mora S et al. Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: a meta-analysis. JAMA 2012; 307(12): 1302–1309. Dostupné z DOI: <http://dx.doi.org/10.1001/jama.2012.366>. Erratum in JAMA 2012; 307(18): 1915. JAMA 2012; 307(16): 1694.
3. Sniderman AD, Wiliams K, Contois JH et al. A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk. Circ Cardiovasc Qual Outcomes 2011; 4(3): 337–345. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCOUTCOMES.110.959247>.
4. Baigent C, Keech A, Kearney PM et al. Efficacy and safety of cholesterol-lowering tretment: prospective meta-analysis of data from 90.056 participants in 14 randomised trials of statins. Lancet 2005: 366(9493): 1267–1278. Erratum in Lancet 2005; 366(9494): 1358. Lancet 2008; 371(9630): 2084.
5. Genser B, Marz W. Low density lipoprotein cholesterol, statins and cardiovascular events: a meta-analysis. Clin Res Cardiol 2006; 95(8): 393–404. Erratum in Clin Res Cardiol 2007; 96(7): 526.
6. Avis HJ, Hutten BA, Gagne C et al. Efficacy and safety of rosuvastatin therapy for children with familial hypercholesterolemia. J Am Coll Cardiol 2010; 55(11): 1121–1126. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2009.10.042>.
7. Seidah NG, Prat A. Precursor convertases in the secretory pathway, cytosol and extracellular milieu. Essays Biochem 2002; 38: 79–94.
8. Seidah NG, Benjannet S, Wickham L et al. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Proc Natl Acad Sci USA 2003; 100(3): 928–933.
9. Naureckiene S, Ma L, Sreekumar K et al. Funtional characterization of NARC-1, a novel proteinase related to proteinase K. Arch Biochem Biophys 2003; 420(1): 55–67.
10. Abifadel M, Varret M, Rabes JP et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 2003; 34(2): 154–156.
11. Allard D, Amsellem S, Abifadel M et al. Novel mutations of the PCSK9 gene cause variable phenotype of autosomal dominant hypercholesterolemia. Hum Mutat 2005; 26(5): 497. Erratum in Hum Mutat 2005; 26(6): 592.
12. Humphries SE, Cranston T, Allen M et al. Mutational analysis in UK patients with a clinical diagnosis of familial hypercholesterolemia: relationship with plasma lipid traits, heart disease risk and utility in relative tracing. J Mol Med (Berl) 2006; 84(2): 203–214.
13. Maxwell KN, Breslow JL. Proprotein convertase subtilisin kexin 9: the third locus implicated in autosomal dominant hypercholesterolemia. Curr Opin Lipidol 2005; 16(2): 167–172.
14. Humphries SE, Whittall RA, Hubbart CS et al. Simon Broome Familial Hyperlipidaemia Register Group and Scientific Steering Committee. Genetic causes of familial hypercholesterolaemia in patients in the UK: relation to plasma lipid levels and coronary heart disease risk. J Med Genet 2006 ;43(12): 943–949. Erratum in J Med Genet 2009; 46(12): 861. J Med Genet 2010; 47(12): 862.
15. Cohen J. Pertsemlidis A, Kotowski IK et al. Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat Genet 2005; 37(2): 161–165. Erratum in Nat Genet 2005; 37(3):328.
16. Cohen JC, Boerwinkle E, Mosley TH Jr et al. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 2006; 354(12): 1264–1272.
17. Benn M, Nordestgaard BG, Grande P et al. PCSK9 R46L, low-density lipoprotein cholesterol levels, and risk of ischmiec heart disease: 3 independent studies and meta-analyses. J Am Coll Cardiol 2010; 55(25): 2833–2842. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2010.02.044>.
18. Chan JC, Piper DE, Cao Q et al. A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates. Proc Natl Acad Sci USA 2009; 106(24): 9820–9825. Dostupné z DOI: <http://dx.doi.org/10.1073/pnas.0903849106>.
19. Zhang L, McCabe T, Condra JH et al. An anti-PCSK9 antibody reduces LDL-cholesterol on top of a statin and suppresses hepatocyte SREBP-regulated genes. Int J Biol Sci 2012; 8(3):310–327. Dostupné z DOI: <http://dx.doi.org/10.7150/ijbs.3524>.
20. Ni YG, Di Marco S, Condra JH et al. A PCSK9-binding antibody that structurally mimics the EGF(A) domain of LDL-receptor reduces LDL cholesterol in vivo. J Lipid Res 2011; 52(1): 78–86. Dostupné z DOI: <http://dx.doi.org/10.1194/jlr.M011445>.
21. Frank-Kamenetsky M, Grefhors A, Anderson NN et al. Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates. Proc Natl Acad Dci USA 2008; 105(33): 11915–11920. Dostupné z DOI: <http://dx.doi.org/10.1073/pnas.0805434105>.
22. Gupta N, Fisker N, Asselin MC et al. A locked nucleic acid antisense oligonucleotide (LNA) silences PCSK9 and enhances LDLR expression in vitro and in vivo. PloS ONE 2010; 5(5): e10682. Dostupné z DOI: <http://dx.doi.org/10.1371/journal.pone.0010682>.
23. Zhang DW, Lagace TA, Garuti R et al. Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation. J Biol Chem 2008; 282(25):18602–18612.
24. Poirier S, Mayer G, Benjannet S et al. The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family members VLDLR and ApoER2. J Biol Chem 2008; 283(4): 2363–2372.
25. McKenney J, Koren MJ, Kereiakes DJ et al. 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): 2344–2353. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2012.03.007>.
26. Giugliano RP, Desai NR, Kohli P et al. [LAPLACE-TIMI 57 Investigators]. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 study. Lancet 2012; 380(9858): 2007–2017. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(12)61770-X>.
27. Blom DJ, Hala T, Bolognese M et al. [DESCARTES Investigators]. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. N Engl J Med 2014; 370(19): 1809–1819. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1316222>.
28. Roth EM, Taskinen MR, Ginsberg HN et al. Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: results of a 24 week, double-blind, randomized Phase 3 trial. Int J Cardiol 2014; 176(1): 55–61. Dostupné z DOI: <http://dx.doi.org/10.1016/j.ijcard.2014.06.049>.
29. Nordestgaard BG, Cahpman MJ, Humphries SE et al. [European Atherosclerosis Society Consensus Panel]. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J 2013; 34(45): 3478–3490a. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/eht273>.
30. Alonso R, Mata N, Castillo S et al. [Spanish Familial Hypercholesterolaemia Group]. Cardiovascular disease in familial hypercholesterolaemia: influence of low-density lipoprotein receptor mutation type and classic risk factors. Atherosclerosis 2008; 200(2): 315–321. Dostupné z DOI: <http://dx.doi.org/10.1016/j.atherosclerosis.2007.12.024>.
31. Kolansky DM, Cuchel M, Clark BJ et al. Longitudinal evaluation and assessment of cardiovascular diseasse in patients with homozygous familial hypercholesterolemia. Am J Cardiol 2008; 102(11): 1438–1443. Dostupné z DOI: <http://dx.doi.org/10.1016/j.amjcard.2008.07.035>.
32. Pijlman AH, Huijgen R, Verhagen SN et al. Evaluation of cholesterol lowering treatment of patients with familial hypercholesterolemia: a large cross-sectional study in The Netherlands. Atherosclerosis 2010; 209(1): 189–194. Dostupné z DOI: <http://dx.doi.org/10.1016/j.atherosclerosis.2009.09.014>.
33. O´Keefe JH Jr, Cordain L, Harris WH et al. Optimal low-density lipoprotein is 50 to 70 mg/dl: lower is better and physiologically normal. J Am Coll Cardiol 2004; 43(11): 2142–2146.
34. Murín J, Pernický M, Wawruch M. Intolerancia statínov. Cardiol Lett 2015; 24(6): 451–457.
35. Toth PP, Harper CR, Jakobson TA. Clinical characterization and molecular mechanisms of statin myopathy. Expert Rev Cardiovasc Ther 2008; 6(7): 955–969. Dostupné z DOI: <http://dx.doi.org/10.1586/14779072.6.7.955>.
Štítky
Angiology Diabetology Internal medicine Cardiology General practitioner for adultsČlánok vyšiel v časopise
Athero Review
2016 Číslo 3
- Memantine Eases Daily Life for Patients and Caregivers
- Metamizole at a Glance and in Practice – Effective Non-Opioid Analgesic for All Ages
- Metamizole vs. Tramadol in Postoperative Analgesia
- Advances in the Treatment of Myasthenia Gravis on the Horizon
- Spasmolytic Effect of Metamizole
Najčítanejšie v tomto čísle
- Arterin® – doplněk stravy v léčbě dyslipidemie: výsledky krátkodobého klinického sledování
- Atherogenic dyslipidemia – a new target in cardiovascular prevention
- Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors
- Peripheral arterial disease (PAD) of lower extremity and dyslipidemia