메뉴 건너뛰기




Volumn 57, Issue 2, 2016, Pages 86-91

PCSK9 inhibition as an emerging lipid lowering therapy: Unanswered questions

Author keywords

Cardiovascular events; Familial hypercholesterolemia; PCSK9 inhibitors

Indexed keywords

ALIROCUMAB; BOCOCIZUMAB; EVOLOCUMAB; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 INHIBITOR; PROTEIN INHIBITOR; UNCLASSIFIED DRUG; ENZYME INHIBITOR; MONOCLONAL ANTIBODY; PCSK9 PROTEIN, HUMAN; PROPROTEIN CONVERTASE 9;

EID: 84981341424     PISSN: 11099666     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.hjc.2016.03.002     Document Type: Review
Times cited : (19)

References (42)
  • 2
    • 84981307110 scopus 로고    scopus 로고
    • updated May
    • WHO Fact sheet N0 310, updated May 2014, http://www.who.int/mediacentre/factsheets/fs310/en/.
    • (2014) WHO Fact Sheet N0 310
  • 3
    • 0026681128 scopus 로고
    • Serum cholesterol level and mortality findings for men screened in the Multiple Risk Factor Intervention Trial. Multiple Risk Factor Intervention Trial Research Group
    • Neaton JD, Blackburn H, Jacobs D, et al. Serum cholesterol level and mortality findings for men screened in the Multiple Risk Factor Intervention Trial. Multiple Risk Factor Intervention Trial Research Group. Arch Intern Med. 1992;152:1490-1500.
    • (1992) Arch Intern Med , vol.152 , pp. 1490-1500
    • Neaton, J.D.1    Blackburn, H.2    Jacobs, D.3
  • 4
    • 34548329882 scopus 로고    scopus 로고
    • European guidelines on cardiovascular disease prevention in clinical practice: Full text. Fourth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts)
    • Graham I, Atar D, Borch-Johnsen K, et al. European guidelines on cardiovascular disease prevention in clinical practice: full text. Fourth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts). Eur J Cardiovasc Prev Rehabil. 2007;14(suppl 2):S1-S113.
    • (2007) Eur J Cardiovasc Prev Rehabil , vol.14 , pp. SS1-S113
    • Graham, I.1    Atar, D.2    Borch-Johnsen, K.3
  • 5
    • 56349154187 scopus 로고    scopus 로고
    • The residual risk Reduction initiative: A call to action to reduce residual vascular risk in patients with dyslipidemia
    • Fruchart J-C, Sacks F, Hermans MP, et al. The residual risk Reduction initiative: a call to action to reduce residual vascular risk in patients with dyslipidemia. Am J Cardiol. 2008;102: 1K-34K.
    • (2008) Am J Cardiol , vol.102 , pp. 1K-34K
    • Fruchart, J.-C.1    Sacks, F.2    Hermans, M.P.3
  • 6
    • 3242823479 scopus 로고
    • Receptor-mediated endocytosis: Insights from the lipoprotein receptor system
    • Brown MS, Goldstein JL. Receptor-mediated endocytosis: insights from the lipoprotein receptor system. Proc Natl Acad Sci USA. 1979;76:3330-3337.
    • (1979) Proc Natl Acad Sci USA , vol.76 , pp. 3330-3337
    • Brown, M.S.1    Goldstein, J.L.2
  • 7
    • 0037603589 scopus 로고    scopus 로고
    • Mutations in PCSK9 cause autosomal dominant hypercholesterolemia
    • Abifadel M, Varret M, Rabes J-P, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003;34:154-156.
    • (2003) Nat Genet , vol.34 , pp. 154-156
    • Abifadel, M.1    Varret, M.2    Rabes, J.-P.3
  • 8
    • 77952684555 scopus 로고    scopus 로고
    • Strong induction of PCSK9 gene expression through HNF1alpha and SREBP2: Mechanism for the resistance to LDL-cholesterol lowering effect of statins in dyslipidemic hamsters
    • Dong B, Wu M, Li H, et al. Strong induction of PCSK9 gene expression through HNF1alpha and SREBP2: mechanism for the resistance to LDL-cholesterol lowering effect of statins in dyslipidemic hamsters. J Lipid Res. 2010;51:1486-1495.
    • (2010) J Lipid Res , vol.51 , pp. 1486-1495
    • Dong, B.1    Wu, M.2    Li, H.3
  • 9
    • 33748661502 scopus 로고    scopus 로고
    • Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote
    • Zhao Z, Tuakli-Wosornu Y, Lagace TA, et al. Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote. Am J Hum Genet. 2006; 79:514-523.
    • (2006) Am J Hum Genet , vol.79 , pp. 514-523
    • Zhao, Z.1    Tuakli-Wosornu, Y.2    Lagace, T.A.3
  • 10
    • 84860383419 scopus 로고    scopus 로고
    • The biology and therapeutic targeting of the proprotein convertases
    • Seidah NG, Prat A. The biology and therapeutic targeting of the proprotein convertases. Nat Rev Drug Discov. 2012;11: 367-383.
    • (2012) Nat Rev Drug Discov , vol.11 , pp. 367-383
    • Seidah, N.G.1    Prat, A.2
  • 11
    • 34247605063 scopus 로고    scopus 로고
    • Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia
    • Cunningham D, Danley DE, Geoghegan KF, et al. Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia. Nat Struct Mol Biol. 2007;14:413-419.
    • (2007) Nat Struct Mol Biol , vol.14 , pp. 413-419
    • Cunningham, D.1    Danley, D.E.2    Geoghegan, K.F.3
  • 12
    • 84926191670 scopus 로고    scopus 로고
    • ODYSSEY LONG TERM Investigators. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events
    • Robinson JG, Farnier M, Krempf M, et al, ODYSSEY LONG TERM Investigators. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372: 1489-1499.
    • (2015) N Engl J Med , vol.372 , pp. 1489-1499
    • Robinson, J.G.1    Farnier, M.2    Krempf, M.3
  • 13
    • 84926206074 scopus 로고    scopus 로고
    • Efficacy and safety of evolocumab in reducing lipids and cardiovascular events
    • Sabatine MS, Giugliano RP, Wiviott SD, et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372:1500-1509.
    • (2015) N Engl J Med , vol.372 , pp. 1500-1509
    • Sabatine, M.S.1    Giugliano, R.P.2    Wiviott, S.D.3
  • 14
    • 84876801739 scopus 로고    scopus 로고
    • The safety of therapeutic monoclonal antibodies: Implications for cardiovascular disease and targeting the PCSK9 pathway
    • Catapano AL, Papadopoulos N. The safety of therapeutic monoclonal antibodies: implications for cardiovascular disease and targeting the PCSK9 pathway. Atherosclerosis. 2013;228: 18-28.
    • (2013) Atherosclerosis , vol.228 , pp. 18-28
    • Catapano, A.L.1    Papadopoulos, N.2
  • 15
    • 33744479185 scopus 로고    scopus 로고
    • Long term efficacy and safety of adalimumab plus methotrexate in patients with rheumatoid arthritis: ARMADA 4 year extended study
    • Weinblatt ME, Keystone EC, Furst DE, Kavanaugh AF, Chartash EK, Segurado OG. Long term efficacy and safety of adalimumab plus methotrexate in patients with rheumatoid arthritis: ARMADA 4 year extended study. Ann Rheum Dis. 2006; 65:753-759.
    • (2006) Ann Rheum Dis , vol.65 , pp. 753-759
    • Weinblatt, M.E.1    Keystone, E.C.2    Furst, D.E.3    Kavanaugh, A.F.4    Chartash, E.K.5    Segurado, O.G.6
  • 16
    • 11144355354 scopus 로고    scopus 로고
    • Intensive versus moderate lipid lowering with statins after acute coronary syndromes
    • Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350:1495-1504.
    • (2004) N Engl J Med , vol.350 , pp. 1495-1504
    • Cannon, C.P.1    Braunwald, E.2    McCabe, C.H.3
  • 17
    • 15944410609 scopus 로고    scopus 로고
    • Intensive lipid lowering with atorvastatin in patients with stable coronary disease
    • LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352:1425-1435.
    • (2005) N Engl J Med , vol.352 , pp. 1425-1435
    • Larosa, J.C.1    Grundy, S.M.2    Waters, D.D.3
  • 18
    • 84865813739 scopus 로고    scopus 로고
    • Effects of huntergatherer subsistence mode on arterial distensibility in Cameroonian pygmies
    • Lemogoum D, Ngatchou W, Janssen C, et al. Effects of huntergatherer subsistence mode on arterial distensibility in Cameroonian pygmies. Hypertension. 2012;60:123-128.
    • (2012) Hypertension , vol.60 , pp. 123-128
    • Lemogoum, D.1    Ngatchou, W.2    Janssen, C.3
  • 19
    • 26844468578 scopus 로고    scopus 로고
    • Can low-density lipoprotein be too low? The safety and efficacy of achieving very low low-density lipoprotein with intensive statin therapy: A PROVE IT-TIMI 22 substudy
    • Wiviott SD, Cannon CP, Morrow DA, Ray KK, Pfeffer MA, Braunwald E. Can low-density lipoprotein be too low? The safety and efficacy of achieving very low low-density lipoprotein with intensive statin therapy: a PROVE IT-TIMI 22 substudy. J Am Coll Cardiol. 2005;46:1411-1416.
    • (2005) J am Coll Cardiol , vol.46 , pp. 1411-1416
    • Wiviott, S.D.1    Cannon, C.P.2    Morrow, D.A.3    Ray, K.K.4    Pfeffer, M.A.5    Braunwald, E.6
  • 20
    • 84912127068 scopus 로고    scopus 로고
    • Safety profile of subjects treated to very low low-density lipoprotein cholesterol levels (<30 mg/dl) with rosuvastatin 20 mg daily (from JUPITER)
    • Everett BM, Mora S, Glynn RJ, MacFadyen J, Ridker PM. Safety profile of subjects treated to very low low-density lipoprotein cholesterol levels (<30 mg/dl) with rosuvastatin 20 mg daily (from JUPITER). Am J Cardiol. 2014;114:1682-1689.
    • (2014) Am J Cardiol , vol.114 , pp. 1682-1689
    • Everett, B.M.1    Mora, S.2    Glynn, R.J.3    Macfadyen, J.4    Ridker, P.M.5
  • 21
    • 84900303213 scopus 로고    scopus 로고
    • 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
    • Robinson JG, Nedergaard BS, Rogers WJ, et al. 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;311:1870-1882.
    • (2014) JAMA , vol.311 , pp. 1870-1882
    • Robinson, J.G.1    Nedergaard, B.S.2    Rogers, W.J.3
  • 22
    • 84929322473 scopus 로고    scopus 로고
    • 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
    • Cannon CP, Cariou B, Blom D, et al, 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.
    • (2015) Eur Heart J , vol.36 , pp. 1186-1194
    • Cannon, C.P.1    Cariou, B.2    Blom, D.3
  • 23
    • 79956315187 scopus 로고    scopus 로고
    • Pleiotropic effects of statins: Evidence for benefits beyond LDL-cholesterol lowering
    • Marzilli M. Pleiotropic effects of statins: evidence for benefits beyond LDL-cholesterol lowering. Am J Cardiovasc Drugs. 2010;10(suppl 1):3-9.
    • (2010) Am J Cardiovasc Drugs , vol.10 , pp. 3-9
    • Marzilli, M.1
  • 24
    • 84897471477 scopus 로고    scopus 로고
    • 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
    • Raal FJ, Giugliano RP, Sabatine MS, 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;63:1278-1288.
    • (2014) J am Coll Cardiol , vol.63 , pp. 1278-1288
    • Raal, F.J.1    Giugliano, R.P.2    Sabatine, M.S.3
  • 25
    • 84908363070 scopus 로고    scopus 로고
    • Effect of alirocumab, a monoclonal proprotein convertase subtilisin/kexin 9 antibody, on lipoprotein(A) concentrations (a pooled analysis of 150 mg every two weeks dosing from phase 2 trials)
    • Gaudet D, Kereiakes DJ, McKenney JM, et al. Effect of alirocumab, a monoclonal proprotein convertase subtilisin/kexin 9 antibody, on lipoprotein(a) concentrations (a pooled analysis of 150 mg every two weeks dosing from phase 2 trials). Am J Cardiol. 2014;114:711-715.
    • (2014) Am J Cardiol , vol.114 , pp. 711-715
    • Gaudet, D.1    Kereiakes, D.J.2    McKenney, J.M.3
  • 26
    • 84897889156 scopus 로고    scopus 로고
    • PCSK9: A key modulator of cardiovascular health
    • Seidah NG, Awan Z, Chrétien M, Mbikay M. PCSK9: a key modulator of cardiovascular health. Circ Res. 2014;114: 1022-1036.
    • (2014) Circ Res , vol.114 , pp. 1022-1036
    • Seidah, N.G.1    Awan, Z.2    Chrétien, M.3    Mbikay, M.4
  • 27
    • 84864206454 scopus 로고    scopus 로고
    • Antibodies to PCSK9: A superior way to lower LDL cholesterol?
    • Maxwell KN, Breslow JL. Antibodies to PCSK9: a superior way to lower LDL cholesterol? Circ Res. 2012;111:274-277.
    • (2012) Circ Res , vol.111 , pp. 274-277
    • Maxwell, K.N.1    Breslow, J.L.2
  • 28
    • 84949009255 scopus 로고    scopus 로고
    • The central role of PCSK9 in septic pathogen lipid transport and clearance
    • Walley KR, Francis GA, Opal SM, et al. The central role of PCSK9 in septic pathogen lipid transport and clearance. Am J Respir Crit Care Med. 2015;1(192):1275-1286.
    • (2015) Am J Respir Crit Care Med , vol.1 , Issue.192 , pp. 1275-1286
    • Walley, K.R.1    Francis, G.A.2    Opal, S.M.3
  • 30
    • 26244432388 scopus 로고    scopus 로고
    • Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: Prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins
    • Baigent C, Keech A, Kearney PM, et al. Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366:1267-1278.
    • (2005) Lancet , vol.366 , pp. 1267-1278
    • Baigent, C.1    Keech, A.2    Kearney, P.M.3
  • 31
    • 84906675153 scopus 로고    scopus 로고
    • Understanding IMPROVE-IT and the cardinal role of LDL-C lowering in CVD prevention
    • Laufs U, Descamps OS, Catapano AL, Packard CJ. Understanding IMPROVE-IT and the cardinal role of LDL-C lowering in CVD prevention. Eur Heart J. 2014;35:1996-2000.
    • (2014) Eur Heart J , vol.35 , pp. 1996-2000
    • Laufs, U.1    Descamps, O.S.2    Catapano, A.L.3    Packard, C.J.4
  • 32
    • 84905189482 scopus 로고    scopus 로고
    • Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: A meta-analysis of statin trials
    • Boekholdt SM, Hovingh GK, Mora S, et al. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials. J Am Coll Cardiol. 2014;64: 485-494.
    • (2014) J am Coll Cardiol , vol.64 , pp. 485-494
    • Boekholdt, S.M.1    Hovingh, G.K.2    Mora, S.3
  • 33
    • 84931411520 scopus 로고    scopus 로고
    • IMPROVE-IT Investigators. Ezetimibe added to statin therapy after acute coronary syndromes
    • Cannon CP, Blazing MA, Giugliano RP, et al. IMPROVE-IT Investigators. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387-2397.
    • (2015) N Engl J Med , vol.372 , pp. 2387-2397
    • Cannon, C.P.1    Blazing, M.A.2    Giugliano, R.P.3
  • 34
    • 84923169850 scopus 로고    scopus 로고
    • Are lower levels of LDL-cholesterol really better? Looking at the results of IMPROVE-IT: Opinions of three experts e II
    • Rallidis LS. Are lower levels of LDL-cholesterol really better? Looking at the results of IMPROVE-IT: opinions of three experts e II. Hellenic J Cardiol. 2015;56:4-6.
    • (2015) Hellenic J Cardiol , vol.56 , pp. 4-6
    • Rallidis, L.S.1
  • 35
    • 84923196210 scopus 로고    scopus 로고
    • Are lower levels of LDL-cholesterol really better? Looking at the results of IMPROVE-IT: Opinions of three experts e III
    • Filippatos TD, Elisaf MS. Are lower levels of LDL-cholesterol really better? Looking at the results of IMPROVE-IT: opinions of three experts e III. Hellenic J Cardiol. 2015;56:7-9.
    • (2015) Hellenic J Cardiol , vol.56 , pp. 7-9
    • Filippatos, T.D.1    Elisaf, M.S.2
  • 36
    • 35549012363 scopus 로고    scopus 로고
    • Current questions regarding the use of statins in patients with coronary heart disease
    • Rallidis LS, Lekakis J, Kremastinos DT. Current questions regarding the use of statins in patients with coronary heart disease. Int J Cardiol. 2007;122:188-194.
    • (2007) Int J Cardiol , vol.122 , pp. 188-194
    • Rallidis, L.S.1    Lekakis, J.2    Kremastinos, D.T.3
  • 37
    • 84959880392 scopus 로고    scopus 로고
    • EUROASPIRE IV: A European Society of Cardiology survey on the lifestyle, risk factor and therapeutic management of coronary patients from 24 European countries
    • Kotseva K, Wood D, De Bacquer D, et al. EUROASPIRE IV: A European Society of Cardiology survey on the lifestyle, risk factor and therapeutic management of coronary patients from 24 European countries. Eur J Prev Cardiol. 2016;23:636-648.
    • (2016) Eur J Prev Cardiol , vol.23 , pp. 636-648
    • Kotseva, K.1    Wood, D.2    De Bacquer, D.3
  • 38
    • 84927742065 scopus 로고    scopus 로고
    • Statin-associated muscle symptoms: Impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management
    • Stroes ES, Thompson PD, Corsini A, et al. Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur Heart J. 2015;36:1012-1022.
    • (2015) Eur Heart J , vol.36 , pp. 1012-1022
    • Stroes, E.S.1    Thompson, P.D.2    Corsini, A.3
  • 39
    • 84865499009 scopus 로고    scopus 로고
    • Managing the underestimated risk of statin-associated myopathy
    • Rallidis LS, Fountoulaki K, Anastasiou-Nana M. Managing the underestimated risk of statin-associated myopathy. Int J Cardiol. 2012;159:169-176.
    • (2012) Int J Cardiol , vol.159 , pp. 169-176
    • Rallidis, L.S.1    Fountoulaki, K.2    Anastasiou-Nana, M.3
  • 40
    • 32444444724 scopus 로고    scopus 로고
    • Be´gaud B. Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patientsethe PRIMO study
    • Bruckert E, Hayem G, Dejager S, Yau C, Be´gaud B. Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patientsethe PRIMO study. Cardiovasc Drugs Ther. 2005;19:403-414.
    • (2005) Cardiovasc Drugs Ther , vol.19 , pp. 403-414
    • Bruckert, E.1    Hayem, G.2    Dejager, S.3    Yau, C.4
  • 41
    • 84902157271 scopus 로고    scopus 로고
    • GAUSS-2 Investigators. Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: The GAUSS-2 randomized, placebocontrolled phase 3 clinical trial of evolocumab
    • Stroes E, Colquhoun D, Sullivan D, et alGAUSS-2 Investigators. Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebocontrolled phase 3 clinical trial of evolocumab. J Am Coll Cardiol. 2014;63:2541-2548.
    • (2014) J am Coll Cardiol , vol.63 , pp. 2541-2548
    • Stroes, E.1    Colquhoun, D.2    Sullivan, D.3
  • 42
    • 84957953328 scopus 로고    scopus 로고
    • National lipid association recommendations for patient-centered management of dyslipidemia: Part 2
    • Jacobson TA, Ito MK, Maki KC, Orringer C, et al. National lipid association recommendations for patient-centered management of dyslipidemia: Part 2. J Clin Lipidol. 2015;9(6 suppl): S1-S122.
    • (2015) J Clin Lipidol , vol.9 , Issue.6 , pp. SS1-S122
    • Jacobson, T.A.1    Ito, M.K.2    Maki, K.C.3    Orringer, C.4


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.