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Journal of Thrombosis and Thrombolysis
Published in: Journal of Thrombosis and Thrombolysis 3/2016

Open Access 01-10-2016

PCSK9 inhibitors in the prevention of cardiovascular disease

Authors: James Latimer, Jonathan A. Batty, R. Dermot G. Neely, Vijay Kunadian

Published in: Journal of Thrombosis and Thrombolysis | Issue 3/2016

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Abstract

Reducing plasma levels of low-density lipoprotein cholesterol (LDL-C) remains the cornerstone in the primary and secondary prevention of cardiovascular disease. However, lack of efficacy and adverse effects mean that a substantial proportion of patients fail to achieve acceptable LDL-C levels with currently available lipid-lowering drugs. Over the last decade, inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic strategy to reduce residual cardiovascular disease risk. Binding of PCSK9 to the LDL receptor targets the receptor for lysosomal degradation. The recognition that inhibition of PCSK9 increases LDL receptor activity has led to the development of a number of approaches to directly target PCSK9. Numerous monoclonal antibodies against PCSK9 are currently being evaluated in phase 3 trials, involving various patient categories on different background lipid-lowering therapies. Current evidence shows reductions in LDL-C levels of up to 70 % may be achieved with PCSK9 inhibition, independent of background statin therapy. This review examines the most recent evidence and future prospects for the use of PCSK9 inhibitors in the prevention of cardiovascular disease.
Literature
1.
Mendis S, Puska P, Norrving B (2011) Global atlas on cardiovascular disease prevention and control. World Health Organization, Geneva
2.
Cholesterol Treatment Trialists C, Baigent C, Blackwell L, Emberson J, Holland LE, Reith C et al (2010) Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 376(9753):1670–1681CrossRef
3.
Cholesterol Treatment Trialists C, Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J et al (2012) The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet 380(9841):581–590CrossRef
4.
5.
Corrao G, Conti V, Merlino L, Catapano AL, Mancia G (2010) Results of a retrospective database analysis of adherence to statin therapy and risk of nonfatal ischemic heart disease in daily clinical practice in Italy. Clin Ther 32(2):300–310PubMedCrossRef
6.
Abifadel M, Varret M, Rabès J-P, Allard D, Ouguerram K, Devillers M et al (2003) Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 34(2):154–156PubMedCrossRef
7.
Graham CA, McIlhatton BP, Kirk CW, Beattie ED, Lyttle K, Hart P et al (2005) Genetic screening protocol for familial hypercholesterolemia which includes splicing defects gives an improved mutation detection rate. Atherosclerosis 182(2):331–340PubMedCrossRef
8.
Seidah NG, Benjannet S, Wickham L, Marcinkiewicz J, Jasmin SB, Stifani S et al (2003) The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Proc Natl Acad Sci 100(3):928–933PubMedPubMedCentralCrossRef
9.
Lambert G, Sjouke B, Choque B, Kastelein JJP, Hovingh GK (2012) The PCSK9 decade thematic review series: new lipid and lipoprotein targets for the treatment of cardiometabolic diseases. J Lipid Res 53(12):2515–2524PubMedPubMedCentralCrossRef
10.
11.
Artenstein AW, Opal SM (2011) Proprotein convertases in health and disease. N Engl J Med 365(26):2507–2518PubMedCrossRef
12.
Maxwell KN, Breslow JL (2004) Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype. Proc Natl Acad Sci USA 101(18):7100–7105PubMedPubMedCentralCrossRef
13.
Seidah NG, Prat A (2012) The biology and therapeutic targeting of the proprotein convertases. Nat Rev Drug Discovery 11(5):367–383PubMedCrossRef
14.
Jeong HJ, Lee H-S, Kim K-S, Kim Y-K, Yoon D, Park SW (2008) Sterol-dependent regulation of proprotein convertase subtilisin/kexin type 9 expression by sterol-regulatory element binding protein-2. J Lipid Res 49(2):399–409PubMedCrossRef
15.
16.
Kosenko T, Golder M, Leblond G, Weng W, Lagace TA (2013) Low density lipoprotein binds to proprotein convertase subtilisin/kexin type-9 (PCSK9) in human plasma and inhibits PCSK9-mediated low density lipoprotein receptor degradation. J Biol Chem 288(12):8279–8288PubMedPubMedCentralCrossRef
17.
Browning JD, Horton JD (2010) Fasting reduces plasma proprotein convertase, subtilisin/kexin type 9 and cholesterol biosynthesis in humans. J Lipid Res 51(11):3359–3363PubMedPubMedCentralCrossRef
18.
Costet P, Cariou B, Lambert G, Lalanne F, Lardeux B, Jarnoux A-L et al (2006) Hepatic PCSK9 expression is regulated by nutritional status via insulin and sterol regulatory element-binding protein 1c. J Biol Chem 281(10):6211–6218PubMedCrossRef
19.
Benjannet S, Rhainds D, Essalmani R, Mayne J, Wickham L, Jin W et al (2004) NARC-1/PCSK9 and its natural mutants zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol. J Biol Chem 279(47):48865–48875CrossRefPubMed
20.
Park SW, Moon Y-A, Horton JD (2004) Post-transcriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin/kexin type 9a in mouse liver. J Biol Chem 279(48):50630–50638PubMedCrossRef
21.
Nassoury N, Blasiole DA, Tebon Oler A, Benjannet S, Hamelin J, Poupon V et al (2007) The cellular trafficking of the secretory proprotein convertase PCSK9 and its dependence on the LDLR. Traffic 8(6):718–732PubMedCrossRef
22.
Lambert G (2007) Unravelling the functional significance of PCSK9. Current opinion in lipidology 18(3):304–309PubMedCrossRef
23.
24.
Desai NR, Kohli P, Giugliano RP, O’Donoghue ML, Somaratne R, Zhou J et al (2013) AMG145, a monoclonal antibody against proprotein convertase subtilisin kexin type 9, significantly reduces lipoprotein(a) in hypercholesterolemic patients receiving statin therapy: an analysis from the LDL-C Assessment with Proprotein Convertase Subtilisin Kexin Type 9 Monoclonal Antibody Inhibition Combined with Statin Therapy (LAPLACE)-Thrombolysis in Myocardial Infarction (TIMI) 57 trial. Circulation 128(9):962–969PubMedCrossRef
25.
Couture F, D’Anjou F, Day R (2011) On the cutting edge of proprotein convertase pharmacology: from molecular concepts to clinical applications. Biomol Concepts 2(5):421–438PubMedPubMedCentralCrossRef
26.
27.
Levy E, Ouadda ABD, Spahis S, Sane AT, Garofalo C, Grenier É et al (2013) PCSK9 plays a significant role in cholesterol homeostasis and lipid transport in intestinal epithelial cells. Atherosclerosis 227(2):297–306PubMedCrossRef
28.
Farnier M (2014) PCSK9: from discovery to therapeutic applications. Archives of cardiovascular diseases 107(1):58–66PubMedCrossRef
29.
30.
Bridge SH, Sheridan DA, Felmlee DJ, Crossey MM, Fenwick FI, Lanyon CV et al (2015) PCSK9, apolipoprotein E and lipoviral particles in chronic hepatitis C genotype 3: evidence for genotype-specific regulation of lipoprotein metabolism. J Hepatol 62(4):763–770PubMedCrossRef
31.
Denis M, Marcinkiewicz J, Zaid A, Gauthier D, Poirier S, Lazure C et al (2012) Gene inactivation of proprotein convertase subtilisin/kexin type 9 reduces atherosclerosis in mice. Circulation 125(7):894–901PubMedCrossRef
32.
Cohen JC, Boerwinkle E, Mosley TH Jr, Hobbs HH (2006) Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 354(12):1264–1272PubMedCrossRef
33.
Persson L, Cao G, Ståhle L, Sjöberg BG, Troutt JS, Konrad RJ et al (2010) Circulating proprotein convertase subtilisin kexin type 9 has a diurnal rhythm synchronous with cholesterol synthesis and is reduced by fasting in humans. Arterioscler Thromb Vasc Biol 30(12):2666–2672PubMedCrossRef
34.
Browning JD, Horton JD (2010) Fasting reduces plasma proprotein convertase, subtilisin/kexin type 9 and cholesterol biosynthesis in humans. J Lipid Res 51(11):3359–3363PubMedPubMedCentralCrossRef
35.
Persson L, Cao G, Stahle L, Sjoberg BG, Troutt JS, Konrad RJ et al (2010) Circulating proprotein convertase subtilisin kexin type 9 has a diurnal rhythm synchronous with cholesterol synthesis and is reduced by fasting in humans. Arterioscler Thromb Vasc Biol 30(12):2666–2672PubMedCrossRef
36.
Maxwell KN, Soccio RE, Duncan EM, Sehayek E, Breslow JL (2003) Novel putative SREBP and LXR target genes identified by microarray analysis in liver of cholesterol-fed mice. J Lipid Res 44(11):2109–2119PubMedCrossRef
37.
Tavori H, Giunzioni I, Linton MF, Fazio S (2013) Loss of plasma proprotein convertase subtilisin/kexin 9 (PCSK9) after lipoprotein apheresis. Circ Res 113(12):1290–1295PubMedPubMedCentralCrossRef
38.
Fan D, Yancey PG, Qiu S, Ding L, Weeber EJ, Linton MF et al (2008) Self-association of human PCSK9 correlates with its LDLR-degrading activity. Biochemistry 47(6):1631–1639PubMedPubMedCentralCrossRef
39.
40.
Leren TP (2014) Sorting an LDL receptor with bound PCSK9 to intracellular degradation. Atherosclerosis 237(1):76–81PubMedCrossRef
41.
Graham MJ, Lemonidis KM, Whipple CP, Subramaniam A, Monia BP, Crooke ST et al (2007) Antisense inhibition of proprotein convertase subtilisin/kexin type 9 reduces serum LDL in hyperlipidemic mice. J Lipid Res 48(4):763–767PubMedCrossRef
42.
Lindholm MW, Elmen J, Fisker N, Hansen HF, Persson R, Moller MR et al (2012) PCSK9 LNA antisense oligonucleotides induce sustained reduction of LDL cholesterol in nonhuman primates. Mol Ther 20(2):376–381PubMedCrossRef
43.
Frank-Kamenetsky M, Grefhorst A, Anderson NN, Racie TS, Bramlage B, Akinc A et al (2008) Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates. Proc Natl Acad Sci USA 105(33):11915–11920PubMedPubMedCentralCrossRef
44.
Duff CJ, Scott MJ, Kirby IT, Hutchinson SE, Martin SL, Hooper NM (2009) Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor. Biochem J 419(3):577–584PubMedPubMedCentralCrossRef
45.
Chan JC, Piper DE, Cao Q, Liu D, King C, Wang W et al (2009) A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates. Proc Natl Acad Sci USA 106(24):9820–9825PubMedPubMedCentralCrossRef
46.
Khera AV, Everett BM, Caulfield MP, Hantash FM, Wohlgemuth J, Ridker PM et al (2014) Lipoprotein(a) concentrations, rosuvastatin therapy, and residual vascular risk: an analysis from the JUPITER trial (justification for the use of statins in prevention: an intervention trial evaluating rosuvastatin). Circulation 129(6):635–642PubMedCrossRef
47.
Rader DJ, Cain W, Ikewaki K, Talley G, Zech LA, Usher D et al (1994) The inverse association of plasma lipoprotein(a) concentrations with apolipoprotein(a) isoform size is not due to differences in Lp(a) catabolism but to differences in production rate. J Clin Invest 93(6):2758–2763PubMedPubMedCentralCrossRef
48.
Koren MJ, Scott R, Kim JB, Knusel B, Liu T, Lei L et al (2012) Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 as monotherapy in patients with hypercholesterolaemia (MENDEL): a randomised, double-blind, placebo-controlled, phase 2 study. Lancet 380(9858):1995–2006PubMedCrossRef
49.
Koren MJ, Lundqvist P, Bolognese M, Neutel JM, Monsalvo ML, Yang J et al (2014) Anti-PCSK9 monotherapy for hypercholesterolemia: the MENDEL-2 randomized, controlled phase III clinical trial of evolocumab. J Am Coll Cardiol 63(23):2531–2540PubMedCrossRef
50.
Giugliano RP, Desai NR, Kohli P, Rogers WJ, Somaratne R, Huang F et al (2012) 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 380(9858):2007–2017PubMedPubMedCentralCrossRef
51.
Giugliano RP, Desai NR, Kohli P, Rogers WJ, Somaratne R, Huang F et al (2012) 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 380(9858):2007–2017PubMedPubMedCentralCrossRef
52.
Robinson JG, Nedergaard BS, Rogers WJ, Fialkow J, Neutel JM, Ramstad D et al (2014) 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 311(18):1870–1882PubMedCrossRef
53.
Blom DJ, Hala T, Bolognese M, Lillestol MJ, Toth PD, Burgess L et al (2014) A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. The New England journal of medicine 370(19):1809–1819PubMedCrossRef
54.
Raal F, Scott R, Somaratne R, Bridges I, Li G, Wasserman SM et al (2012) Low-density lipoprotein cholesterol-lowering effects of AMG 145, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease in patients with heterozygous familial hypercholesterolemia: the reduction of LDL-C with PCSK9 inhibition in heterozygous familial hypercholesterolemia disorder (RUTHERFORD) randomized trial. Circulation 126(20):2408–2417PubMedCrossRef
55.
Raal FJ, Stein EA, Dufour R, Turner T, Civeira F, Burgess L et al (2015) PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial. Lancet 385(9965):331–340PubMedCrossRef
56.
Hobbs HH, Brown MS, Goldstein JL (1992) Molecular genetics of the LDL receptor gene in familial hypercholesterolemia. Hum Mutat 1(6):445–466PubMedCrossRef
57.
Raal FJ, Honarpour N, Blom DJ, Hovingh GK, Xu F, Scott R et al (2015) Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial. Lancet 385(9965):341–350PubMedCrossRef
58.
Alfirevic A, Neely D, Armitage J, Chinoy H, Cooper RG, Laaksonen R et al (2014) Phenotype standardization for statin-induced myotoxicity. Clin Pharmacol Ther 96(4):470–476PubMedPubMedCentralCrossRef
59.
Bruckert E, Hayem G, Dejager S, Yau C, Bégaud B (2005) Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients—the PRIMO study. Cardiovasc Drugs Ther 19(6):403–414PubMedCrossRef
60.
Zhang H, Plutzky J, Skentzos S, Morrison F, Mar P, Shubina M et al (2013) Discontinuation of statins in routine care settings: a cohort study. Ann Intern Med 158(7):526–534PubMedPubMedCentralCrossRef
61.
Sullivan D, Olsson AG, Scott R, Kim JB, Xue A, Gebski V et al (2012) Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: the GAUSS randomized trial. JAMA 308(23):2497–2506PubMedCrossRef
62.
Stroes E, Colquhoun D, Sullivan D, Civeira F, Rosenson RS, Watts GF et al (2014) Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab. J Am Coll Cardiol 63(23):2541–2548PubMedCrossRef
63.
Cho L, Rocco M, Colquhoun D, Sullivan D, Rosenson RS, Dent R et al (2014) Design and rationale of the GAUSS-2 study trial: a double-blind, ezetimibe-controlled phase 3 study of the efficacy and tolerability of evolocumab (AMG 145) in subjects with hypercholesterolemia who are intolerant of statin therapy. Clin Cardiol 37(3):131–139PubMedCrossRef
64.
Stein EA, Gipe D, Bergeron J, Gaudet D, Weiss R, Dufour R et al (2012) 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 380(9836):29–36PubMedCrossRef
65.
Farnier M, Kastelein JJP, Roth E, Taskinen MR, Ginsberg HN, Colhoun HM et al (2014) Relationship between alirocumab, PCSK9 and LDL-C levels: results from the odyssey mono phase 3 trial of alirocumab 75 mg every 2 weeks. Atherosclerosis 235(2):e34–e35CrossRef
66.
Kereiakes DJ, Robinson JG, Cannon CP, Lorenzato C, Pordy R, Chaudhari U, et al. (2015) Efficacy and safety of the PCSK9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: the ODYSSEY COMBO I study. Am Heart J
67.
Colhoun HM, Robinson JG, Farnier M, Cariou B, Blom D, Kereiakes DJ et al (2014) Efficacy and safety of alirocumab, a fully human PCSK9 monoclonal antibody, in high cardiovascular risk patients with poorly controlled hypercholesterolemia on maximally tolerated doses of statins: rationale and design of the ODYSSEY COMBO I and II trials. BMC Cardiovasc Disord 14(1):121PubMedPubMedCentralCrossRef
68.
Schwartz GG, Bessac L, Berdan LG, Bhatt DL, Bittner V, Diaz R et al (2014) 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 168(5):682–689PubMedCrossRef
69.
Bays H, Gaudet D, Weiss R, Ruiz JL, Watts GF, Gouni-Berthold I et al (2015) Alirocumab as add-on to atorvastatin versus other lipid treatment strategies: ODYSSEY OPTIONS I randomized trial. J Clin Endocrinol Metabol 100(8):3140–3148CrossRef
70.
Kastelein JJP, Robinson JG, Farnier M, Krempf M, Langslet G, Lorenzato C et al (2014) Efficacy and safety of alirocumab in patients with heterozygous familial hypercholesterolemia not adequately controlled with current lipid-lowering therapy: design and rationale of the ODYSSEY FH studies. Cardiovasc Drugs Ther 28(3):281–289PubMedPubMedCentralCrossRef
71.
Roth EM, Diller P (2014) Alirocumab for hyperlipidemia: physiology of PCSK9 inhibition, pharmacodynamics and Phase I and II clinical trial results of a PCSK9 monoclonal antibody. Future Cardiol 10(2):183–199PubMedCrossRef
72.
Ginsberg HN, Rader D, Raal FJ, Guyton J, Lorenzato C, Pordy R et al (2014) ODYSSEY high FH: efficacy and safety of alirocumab in patients with severe heterozygous familial hypercholesterolemia. Circulation 130(23):2119
73.
Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M et al (2015) Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med 372(16):1489–1499PubMedCrossRef
74.
Kastelein JJP, Ginsberg HN, Langslet G, Hovingh GK, Ceska R, Dufour R et al (2015) ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur Heart J 36(43):2996–3003PubMedPubMedCentral
75.
Cicero AF, Tartagni E, Ertek S (2014) Safety and tolerability of injectable lipid-lowering drugs: a review of available clinical data. Exp Opin Drug Saf 13(8):1023–1030CrossRef
76.
Roth EM, Taskinen MR, Ginsberg HN, Kastelein JJ, Colhoun HM, Robinson JG et al (2014) 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 176(1):55–61PubMedCrossRef
77.
Roth EM, McKenney JM, Hanotin C, Asset G, Stein EA (2012) Atorvastatin with or without an antibody to PCSK9 in primary hypercholesterolemia. N Engl J Med 367(20):1891–1900PubMedCrossRef
78.
McKenney JM, Koren MJ, Kereiakes DJ, Hanotin C, Ferrand AC, Stein EA (2012) 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 59(25):2344–2353PubMedCrossRef
79.
Sabatine MS, Giugliano RP, Wiviott SD, Raal FJ, Blom DJ, Robinson J et al (2015) Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med 372(16):1500–1509PubMedCrossRef
80.
Prospective Studies C (2007) Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55 000 vascular deaths. Lancet 370(9602):1829–1839CrossRef
81.
Zhao Z, Tuakli-Wosornu Y, Lagace TA, Kinch L, Grishin NV, Horton JD et al (2006) Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote. Am J Hum Genet 79(3):514–523PubMedPubMedCentralCrossRef
82.
The Institute for Clinical and Economic Review (ICER) (2015) PCSK9 inhibitor therapies for high cholesterol: effectiveness, value, and value-based price benchmarks (draft). The Institute for Clinical and Economic Review (ICER), Boston
83.
Schulman KA, Balu S, Reed SD (2015) Specialty pharmaceuticals for hyperlipidemia—impact on insurance premiums. N Engl J Med 373(17):1591–1593PubMedCrossRef
84.
Preiss D, Seshasai SR, Welsh P, Murphy SA, Ho JE, Waters DD et al (2011) Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA 305(24):2556–2564PubMedCrossRef
85.
Hirayama A, Honarpour N, Yoshida M, Yamashita S, Huang F, Wasserman SM et al (2014) Effects of evolocumab (AMG 145), a monoclonal antibody to PCSK9, in hypercholesterolemic, statin-treated Japanese patients at high cardiovascular risk–primary results from the phase 2 YUKAWA study. Circ J 78(5):1073–1082PubMedCrossRef
Metadata
Title
PCSK9 inhibitors in the prevention of cardiovascular disease
Authors
James Latimer
Jonathan A. Batty
R. Dermot G. Neely
Vijay Kunadian
Publication date
01-10-2016
Publisher
Springer US
Published in
Journal of Thrombosis and Thrombolysis / Issue 3/2016
Print ISSN: 0929-5305
Electronic ISSN: 1573-742X
DOI
https://doi.org/10.1007/s11239-016-1364-1

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