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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Review Article

PCSK9 Inhibition in Atherosclerotic Cardiovascular Disease

Author(s): Dimitrios Delialis, Maria-Angeliki Dimopoulou, Maria Papaioannou, Georgia Kotsira, Eleni Maneta, Georgios Mavraganis, Christos Loutos, Georgios Georgiopoulos and Kimon Stamatelopoulos*

Volume 29, Issue 23, 2023

Published on: 20 April, 2023

Page: [1802 - 1824] Pages: 23

DOI: 10.2174/1381612829666230412105238

Price: $65

Abstract

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) represent a novel class of hypolipidemic drugs, providing an additional therapeutic option over conventional hypolipidemic treatments. Given the constantly lowering recommended LDL-C goals, low goal achievement rate and low compliance with treatment, new hypolipidemic drug classes may substantially contribute to residual risk reduction for atherosclerotic cardiovascular disease (ASCVD). This review aims to summarize contemporary evidence on the clinical role of PCSK9i in ASCVD prevention. PubMed and MEDLINE databases were searched for keywords in studies on PCSK9i and ASCVD. Approved PCSK9i are the monoclonal antibodies (Mabs), evolocumab and alirocumab, targeting PCSK9, and inclisiran, a small interfering RNA inhibiting PSCK9 synthesis. Overall, PCSK9i effectively reduced LDL-C and other atherogenic lipoproteins, including apolipoprotein B and lipoprotein( a) primarily. PSCK9i Mabs improved imaging markers reflecting coronary atherosclerotic plaque vulnerability and reduced ASCVD events in high-risk patients after short-term treatment (< 3 years follow-up). They are currently indicated as a third-line treatment for secondary prevention and primary prevention in patients with familial hypercholesterolemia at high risk of not achieving their LDL-C goals. Patients with higher baseline ASCVD risk receive greater benefits from PCSK9i. Recent evidence suggests that evolocumab was effective and safe after long-term treatment. Ongoing trials investigate new therapeutic indications for PCSK9i while their cost-effectiveness is still being considered. PCSK9i is a novel hypolipidemic drug class currently indicated for reducing residual risk in secondary ASCVD prevention and high-risk patients.

« Previous Next »
[1]
Roth GA, Mensah GA, Johnson CO, et al. Global burden of cardiovascular diseases and risk factors, 1990-2019. J Am Coll Cardiol 2020; 76(25): 2982-3021.
[http://dx.doi.org/10.1016/j.jacc.2020.11.010] [PMID: 33309175]
[2]
Greaves O, Harrison SL, Lane DA, Banach M, Mastej M, Jozwiak JJ. Cardiovascular primary prevention risk factors in a nationwide survey, ABC (atrial fibrillation, high blood pressure and high cholesterol) risk factors in the LIPIDOGRAM2015 study. Eur Heart J 2021; 42(S1): ehab 724-2471.
[3]
Kavousi M, Leening MJG, Nanchen D, et al. Comparison of application of the ACC/AHA guidelines, Adult Treatment Panel III guidelines, and European Society of Cardiology guidelines for cardiovascular disease prevention in a European cohort. JAMA 2014; 311(14): 1416-23.
[http://dx.doi.org/10.1001/jama.2014.2632] [PMID: 24681960]
[4]
Wong ND, Zhao Y, Quek RGW, et al. Residual atherosclerotic cardiovascular disease risk in statin-treated adults: The multi-ethnic study of atherosclerosis. J Clin Lipidol 2017; 11(5): 1223-33.
[http://dx.doi.org/10.1016/j.jacl.2017.06.015] [PMID: 28754224]
[5]
Visseren FLJ, Mach F, Smulders YM, et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J 2021; 42(34): 3227-337.
[http://dx.doi.org/10.1093/eurheartj/ehab484] [PMID: 34458905]
[6]
Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: Executive Summary. J Am Coll Cardiol 2019; 74(10): 1376-414.
[http://dx.doi.org/10.1016/j.jacc.2019.03.009] [PMID: 30894319]
[7]
Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020; 41(1): 111-88.
[http://dx.doi.org/10.1093/eurheartj/ehz455] [PMID: 31504418]
[8]
Abifadel M, Varret M, Rabès JP, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 2003; 34(2): 154-6.
[http://dx.doi.org/10.1038/ng1161] [PMID: 12730697]
[9]
Roth EM, Davidson MH. PCSK9 inhibitors: Mechanism of action, efficacy, and safety. Rev Cardiovasc Med 2018; 19(S1): 31-46.
[http://dx.doi.org/10.3909/ricm19S1S0002] [PMID: 30207556]
[10]
Brown MS, Herz J, Goldstein JL. Calcium cages, acid baths and recycling receptors. Nature 1997; 388(6643): 629-30.
[http://dx.doi.org/10.1038/41672] [PMID: 9262394]
[11]
Shapiro MD, Fazio S. From lipids to inflammation. Circ Res 2016; 118(4): 732-49.
[http://dx.doi.org/10.1161/CIRCRESAHA.115.306471] [PMID: 26892970]
[12]
Seidah NG, Awan Z, Chrétien M, Mbikay M. PCSK9: A key modulator of cardiovascular health. Circ Res 2014; 114(6): 1022-36.
[http://dx.doi.org/10.1161/CIRCRESAHA.114.301621] [PMID: 24625727]
[13]
Lagace TA, Curtis DE, Garuti R, et al. Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and inlivers of parabiotic mice. J Clin Invest 2006; 116(11): 2995-3005.
[http://dx.doi.org/10.1172/JCI29383] [PMID: 17080197]
[14]
Tavori H, Fan D, Blakemore JL, et al. Serum proprotein convertase subtilisin/kexin type 9 and cell surface low-density lipoprotein receptor: Evidence for a reciprocal regulation. Circulation 2013; 127(24): 2403-13.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.113.001592] [PMID: 23690465]
[15]
Rosenson RS, Hegele RA, Fazio S, Cannon CP. The evolving future of PCSK9 inhibitors. J Am Coll Cardiol 2018; 72(3): 314-29.
[http://dx.doi.org/10.1016/j.jacc.2018.04.054] [PMID: 30012326]
[16]
Zaid A, Roubtsova A, Essalmani R, et al. Proprotein convertase subtilisin/kexin type 9 (PCSK9): Hepatocyte-specific low-density lipoprotein receptor degradation and critical role in mouse liver regeneration. Hepatology 2008; 48(2): 646-54.
[http://dx.doi.org/10.1002/hep.22354] [PMID: 18666258]
[17]
Jang HD, Lee SE, Yang J, et al. Cyclase-associated protein 1 is a binding partner of proprotein convertase subtilisin/kexin type-9 and is required for the degradation of low-density lipoprotein receptors by proprotein convertase subtilisin/kexin type-9. Eur Heart J 2020; 41(2): 239-52.
[http://dx.doi.org/10.1093/eurheartj/ehz566] [PMID: 31419281]
[18]
Ding Z, Pothineni NVK, Goel A, Lüscher TF, Mehta JL. PCSK9 and inflammation: Role of shear stress, pro-inflammatory cytokines, and LOX-1. Cardiovasc Res 2020; 116(5): 908-15.
[http://dx.doi.org/10.1093/cvr/cvz313] [PMID: 31746997]
[19]
Ding Z, Liu S, Wang X, et al. PCSK9 regulates expression of scavenger receptors and ox-LDL uptake in macrophages. Cardiovasc Res 2018; 114(8): 1145-53.
[http://dx.doi.org/10.1093/cvr/cvy079] [PMID: 29617722]
[20]
Tang ZH, Peng J, Ren Z, et al. New role of PCSK9 in atherosclerotic inflammation promotion involving the TLR4/NF-κB pathway. Atherosclerosis 2017; 262: 113-22.
[http://dx.doi.org/10.1016/j.atherosclerosis.2017.04.023] [PMID: 28535426]
[21]
Ding Z, Liu S, Wang X, et al. Cross-talk between LOX-1 and PCSK9 in vascular tissues. Cardiovasc Res 2015; 107(4): 556-67.
[http://dx.doi.org/10.1093/cvr/cvv178] [PMID: 26092101]
[22]
Barale C, Melchionda E, Morotti A, Russo I. PCSK9 biology and its role in atherothrombosis. Int J Mol Sci 2021; 22(11): 5880.
[http://dx.doi.org/10.3390/ijms22115880] [PMID: 34070931]
[23]
Li J, Liang X, Wang Y, Xu Z, Li G. Investigation of highly expressed PCSK9 in atherosclerotic plaques and ox-LDL-induced endothelial cell apoptosis. Mol Med Rep 2017; 16(2): 1817-25.
[http://dx.doi.org/10.3892/mmr.2017.6803] [PMID: 28656218]
[24]
Camera M, Rossetti L, Barbieri SS, et al. PCSK9 as a positive modulator of platelet activation. J Am Coll Cardiol 2018; 71(8): 952-4.
[http://dx.doi.org/10.1016/j.jacc.2017.11.069] [PMID: 29471945]
[25]
Navarese EP, Kolodziejczak M, Winter MP, et al. Association of PCSK9 with platelet reactivity in patients with acute coronary syndrome treated with prasugrel or ticagrelor: The PCSK9-REACT study. Int J Cardiol 2017; 227: 644-9.
[http://dx.doi.org/10.1016/j.ijcard.2016.10.084] [PMID: 27810295]
[26]
Seidah NG, Prat A, Pirillo A, Catapano AL, Norata GD. Novel strategies to target proprotein convertase subtilisin kexin 9: Beyond monoclonal antibodies. Cardiovasc Res 2019; 115(3): 510-8.
[http://dx.doi.org/10.1093/cvr/cvz003] [PMID: 30629143]
[27]
Casula M, Olmastroni E, Boccalari MT, Tragni E, Pirillo A, Catapano AL. Cardiovascular events with PCSK9 inhibitors: An updated meta-analysis of randomised controlled trials. Pharmacol Res 2019; 143: 143-50.
[http://dx.doi.org/10.1016/j.phrs.2019.03.021] [PMID: 30926528]
[28]
Lamb YN. Inclisiran: First approval. Drugs 2021; 81(3): 389-95.
[http://dx.doi.org/10.1007/s40265-021-01473-6] [PMID: 33620677]
[29]
Fitzgerald K, White S, Borodovsky A, et al. A highly durable RNAi therapeutic inhibitor of PCSK9. N Engl J Med 2017; 376(1): 41-51.
[http://dx.doi.org/10.1056/NEJMoa1609243] [PMID: 27959715]
[30]
Pan Y, Zhou Y, Wu H, et al. A therapeutic peptide vaccine against PCSK9. Sci Rep 2017; 7(1): 12534.
[http://dx.doi.org/10.1038/s41598-017-13069-w] [PMID: 28970592]
[31]
Chadwick AC, Wang X, Musunuru K. in vivo base editing of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) as a therapeutic alternative to genome editing. Arterioscler Thromb Vasc Biol 2017; 37(9): 1741-7.
[http://dx.doi.org/10.1161/ATVBAHA.117.309881] [PMID: 28751571]
[32]
Weider E, Susan-Resiga D, Essalmani R, et al. Proprotein convertase subtilisin/Kexin type 9 (PCSK9) single domain antibodies are potent inhibitors of low density lipoprotein receptor degradation. J Biol Chem 2016; 291(51): 26586.
[http://dx.doi.org/10.1074/jbc.A116.717736] [PMID: 27986868]
[33]
Zhang Y, Eigenbrot C, Zhou L, et al. Identification of a small peptide that inhibits PCSK9 protein binding to the low density lipoprotein receptor. J Biol Chem 2014; 289(2): 942-55.
[http://dx.doi.org/10.1074/jbc.M113.514067] [PMID: 24225950]
[34]
Evison BJ, Palmer JT, Lambert G, et al. A small molecule inhibitor of PCSK9 that antagonizes LDL receptor binding via interaction with a cryptic PCSK9 binding groove. Bioorg Med Chem 2020; 28(6): 115344.
[http://dx.doi.org/10.1016/j.bmc.2020.115344] [PMID: 32051094]
[35]
Kawakami R, Nozato Y, Nakagami H, et al. Development of vaccine for dyslipidemia targeted to a proprotein convertase subtilisin/kexin type 9 (PCSK9) epitope in mice. PLoS One 2018; 13(2): e0191895.
[http://dx.doi.org/10.1371/journal.pone.0191895] [PMID: 29438441]
[36]
Ding Q, Strong A, Patel KM, et al. Permanent alteration of PCSK9 with in vivo CRISPR-Cas9 genome editing. Circ Res 2014; 115(5): 488-92.
[http://dx.doi.org/10.1161/CIRCRESAHA.115.304351] [PMID: 24916110]
[37]
Wang X, Raghavan A, Chen T, et al. CRISPR-Cas9 targeting of PCSK9 in human hepatocytes in vivo-brief report. Arterioscler Thromb Vasc Biol 2016; 36(5): 783-6.
[http://dx.doi.org/10.1161/ATVBAHA.116.307227] [PMID: 26941020]
[38]
Rossidis AC, Stratigis JD, Chadwick AC, et al. In utero CRISPR-mediated therapeutic editing of metabolic genes. Nat Med 2018; 24(10): 1513-8.
[http://dx.doi.org/10.1038/s41591-018-0184-6] [PMID: 30297903]
[39]
Essalmani R, Weider E, Marcinkiewicz J, et al. A single domain antibody against the Cys- and His-rich domain of PCSK9 and evolocumab exhibit different inhibition mechanisms in humanized PCSK9 mice. Biol Chem 2018; 399(12): 1363-74.
[http://dx.doi.org/10.1515/hsz-2018-0194] [PMID: 30044755]
[40]
Li X, Wang M, Zhang X, et al. The novel llama-human chimeric antibody has potent effect in lowering LDL-c levels in hPCSK9 transgenic rats. Clin Transl Med 2020; 9(1): 16.
[http://dx.doi.org/10.1186/s40169-020-0265-2] [PMID: 32056048]
[41]
Shan L, Pang L, Zhang R, Murgolo NJ, Lan H, Hedrick JA. PCSK9 binds to multiple receptors and can be functionally inhibited by an EGF-A peptide. Biochem Biophys Res Commun 2008; 375(1): 69-73.
[http://dx.doi.org/10.1016/j.bbrc.2008.07.106] [PMID: 18675252]
[42]
Palmer-Smith H, Basak A. Regulatory effects of peptides from the pro and catalytic domains of proprotein convertase subtilisin/kexin 9 (PCSK9) on low-density lipoprotein receptor (LDL-R). Curr Med Chem 2010; 17(20): 2168-82.
[http://dx.doi.org/10.2174/092986710791299948] [PMID: 20423303]
[43]
Johannesen CDL, Mortensen MB, Langsted A, Nordestgaard BG. Apolipoprotein B and non-HDL cholesterol better reflect residual risk than LDL cholesterol in statin-treated patients. J Am Coll Cardiol 2021; 77(11): 1439-50.
[http://dx.doi.org/10.1016/j.jacc.2021.01.027] [PMID: 33736827]
[44]
Castañer O, Pintó X, Subirana I, et al. Remnant cholesterol, Not LDL cholesterol, is associated with incident cardiovascular disease. J Am Coll Cardiol 2020; 76(23): 2712-24.
[http://dx.doi.org/10.1016/j.jacc.2020.10.008] [PMID: 33272365]
[45]
Saeed A, Feofanova EV, Yu B, et al. Remnant-like particle cholesterol, low-density lipoprotein triglycerides, and incident cardiovascular disease. J Am Coll Cardiol 2018; 72(2): 156-69.
[http://dx.doi.org/10.1016/j.jacc.2018.04.050] [PMID: 29976289]
[46]
Watts GF, Chan DC, Somaratne R, et al. Controlled study of the effect of proprotein convertase subtilisin-kexin type 9 inhibition with evolocumab on lipoprotein(a) particle kinetics. Eur Heart J 2018; 39(27): 2577-85.
[http://dx.doi.org/10.1093/eurheartj/ehy122] [PMID: 29566128]
[47]
Morise AP, Tennant J, Holmes SD, Tacker DH. The effect of proprotein convertase subtilisin/kexin type 9 inhibitors on nonfasting remnant cholesterol in a real world population. J Lipids 2018; 2018: 9194736.
[http://dx.doi.org/10.1155/2018/9194736] [PMID: 30105099]
[48]
Lorenzatti AJ, Monsalvo ML, López JAG, Wang H, Rosenson RS. Effects of evolocumab in individuals with type 2 diabetes with and without atherogenic dyslipidemia: An analysis from BANTING and BERSON. Cardiovasc Diabetol 2021; 20(1): 94.
[http://dx.doi.org/10.1186/s12933-021-01287-6] [PMID: 33941192]
[49]
Toth PP, Hamon SC, Jones SR, et al. Effect of alirocumab on specific lipoprotein non-high-density lipoprotein cholesterol and subfractions as measured by the vertical auto profile method: Analysis of 3 randomized trials versus placebo. Lipids Health Dis 2016; 15(1): 28.
[http://dx.doi.org/10.1186/s12944-016-0197-4] [PMID: 26872608]
[50]
Reyes-Soffer G, Ginsberg HN, Berglund L, et al. Lipoprotein(a): A genetically determined, causal, and prevalent risk factor for atherosclerotic cardiovascular disease: A scientific statement from the American Heart Association. Arterioscler Thromb Vasc Biol 2022; 42(1): e48-60.
[http://dx.doi.org/10.1161/ATV.0000000000000147] [PMID: 34647487]
[51]
Reyes-Soffer G, Ginsberg HN, Ramakrishnan R. The metabolism of lipoprotein(a): An ever-evolving story. J Lipid Res 2017; 58(9): 1756-64.
[http://dx.doi.org/10.1194/jlr.R077693] [PMID: 28720561]
[52]
Croyal M, Tran TTT, Blanchard RH, et al. PCSK9 inhibition with alirocumab reduces lipoprotein(a) levels in nonhuman primates by lowering apolipoprotein(a) production rate. Clin Sci 2018; 132(10): 1075-83.
[http://dx.doi.org/10.1042/CS20180040] [PMID: 29724769]
[53]
Reiter-Brennan C, Osei AD, Iftekhar Uddin SM, et al. ACC/AHA lipid guidelines: Personalized care to prevent cardiovascular disease. Cleve Clin J Med 2020; 87(4): 231-9.
[http://dx.doi.org/10.3949/ccjm.87a.19078] [PMID: 32238379]
[54]
Koren MJ, Lundqvist P, Bolognese M, et al. Anti-PCSK9 monotherapy for hypercholesterolemia: The MENDEL-2 randomized, controlled phase III clinical trial of evolocumab. J Am Coll Cardiol 2014; 63(23): 2531-40.
[http://dx.doi.org/10.1016/j.jacc.2014.03.018] [PMID: 24691094]
[55]
Koren MJ, Scott R, Kim JB, et al. 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 2012; 380(9858): 1995-2006.
[http://dx.doi.org/10.1016/S0140-6736(12)61771-1] [PMID: 23141812]
[56]
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(18): 1870-82.
[http://dx.doi.org/10.1001/jama.2014.4030] [PMID: 24825642]
[57]
Giugliano RP, Desai NR, Kohli P, et al. 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): 2007-17.
[http://dx.doi.org/10.1016/S0140-6736(12)61770-X] [PMID: 23141813]
[58]
Hirayama A, Honarpour N, Yoshida M, et al. 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 2014; 78(5): 1073-82.
[http://dx.doi.org/10.1253/circj.CJ-14-0130] [PMID: 24662398]
[59]
Boccara F, Kumar PN, Caramelli B, et al. Evolocumab in HIV-infected patients with dyslipidemia. J Am Coll Cardiol 2020; 75(20): 2570-84.
[http://dx.doi.org/10.1016/j.jacc.2020.03.025] [PMID: 32234462]
[60]
So-Armah K, Benjamin LA, Bloomfield GS, et al. HIV and cardiovascular disease. Lancet HIV 2020; 7(4): e279-93.
[http://dx.doi.org/10.1016/S2352-3018(20)30036-9] [PMID: 32243826]
[61]
Raal FJ, Stein EA, Dufour R, et al. PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): A randomised, double-blind, placebo-controlled trial. Lancet 2015; 385(9965): 331-40.
[http://dx.doi.org/10.1016/S0140-6736(14)61399-4] [PMID: 25282519]
[62]
Raal F, Scott R, Somaratne R, et al. 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 2012; 126(20): 2408-17.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.112.144055] [PMID: 23129602]
[63]
Raal FJ, Honarpour N, Blom DJ, et al. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): A randomised, double-blind, placebo-controlled trial. Lancet 2015; 385(9965): 341-50.
[http://dx.doi.org/10.1016/S0140-6736(14)61374-X] [PMID: 25282520]
[64]
Santos RD, Ruzza A, Hovingh GK, et al. Evolocumab in pediatric heterozygous familial hypercholesterolemia. N Engl J Med 2020; 383(14): 1317-27.
[http://dx.doi.org/10.1056/NEJMoa2019910] [PMID: 32865373]
[65]
Chen Y, Yuan Z, Lu J, et al. Randomized study of evolocumab in patients with type 2 diabetes and dyslipidaemia on background statin: Pre-specified analysis of the Chinese population from the BERSON clinical trial. Diabetes Obes Metab 2019; 21(6): 1464-73.
[http://dx.doi.org/10.1111/dom.13700] [PMID: 30851062]
[66]
Blom DJ, Hala T, Bolognese M, et al. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. N Engl J Med 2014; 370(19): 1809-19.
[http://dx.doi.org/10.1056/NEJMoa1316222] [PMID: 24678979]
[67]
Blom DJ, Koren MJ, Roth E, et al. Evaluation of the efficacy, safety and glycaemic effects of evolocumab (AMG 145) in hypercholesterolaemic patients stratified by glycaemic status and metabolic syndrome. Diabetes Obes Metab 2017; 19(1): 98-107.
[http://dx.doi.org/10.1111/dom.12788] [PMID: 27619750]
[68]
Nissen SE, Dent-Acosta RE, Rosenson RS, et al. Comparison of PCSK9 inhibitor evolocumab vs. ezetimibe in statin-intolerant patients: Design of the goal achievement after utilizing an Anti-PCSK9 antibody in statin-intolerant subjects 3 (GAUSS-3) trial. Clin Cardiol 2016; 39(3): 137-44.
[http://dx.doi.org/10.1002/clc.22518] [PMID: 26946077]
[69]
Koba S, Inoue I, Cyrille M, et al. Evolocumab vs. ezetimibe in statin-intolerant hyperlipidemic japanese patients: Phase 3 GAUSS-4 trial. J Atheroscler Thromb 2020; 27(5): 471-84.
[http://dx.doi.org/10.5551/jat.50963] [PMID: 31748467]
[70]
Stroes E, Colquhoun D, Sullivan D, et al. 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 2014; 63(23): 2541-8.
[http://dx.doi.org/10.1016/j.jacc.2014.03.019] [PMID: 24694531]
[71]
Sullivan D, Olsson AG, Scott R, et al. Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: The GAUSS randomized trial. JAMA 2012; 308(23): 2497-506.
[http://dx.doi.org/10.1001/jama.2012.25790] [PMID: 23128163]
[72]
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(16): 1500-9.
[http://dx.doi.org/10.1056/NEJMoa1500858] [PMID: 25773607]
[73]
Ballantyne CM, Neutel J, Cropp A, et al. Results of bococizumab, a monoclonal antibody against proprotein convertase subtilisin/kexin type 9, from a randomized, placebo-controlled, dose-ranging study in statin-treated subjects with hypercholesterolemia. Am J Cardiol 2015; 115(9): 1212-21.
[http://dx.doi.org/10.1016/j.amjcard.2015.02.006] [PMID: 25784512]
[74]
Ridker PM, Tardif JC, Amarenco P, et al. Lipid-reduction variability and antidrug-antibody formation with bococizumab. N Engl J Med 2017; 376(16): 1517-26.
[http://dx.doi.org/10.1056/NEJMoa1614062] [PMID: 28304227]
[75]
Kastelein JJP, Nissen SE, Rader DJ, et al. Safety and efficacy of LY3015014, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9): A randomized, placebo-controlled Phase 2 study. Eur Heart J 2016; 37(17): 1360-9.
[http://dx.doi.org/10.1093/eurheartj/ehv707] [PMID: 26757788]
[76]
Schroeder KM, Beyer TP, Hansen RJ, et al. Proteolytic cleavage of antigen extends the durability of an anti-PCSK9 monoclonal antibody. J Lipid Res 2015; 56(11): 2124-32.
[http://dx.doi.org/10.1194/jlr.M061903] [PMID: 26392590]
[77]
Jain M, Carlson G, Cook W, et al. Randomised, phase 1, dose-finding study of MEDI4166, a PCSK9 antibody and GLP-1 analogue fusion molecule, in overweight or obese patients with type 2 diabetes mellitus. Diabetologia 2019; 62(3): 373-86.
[http://dx.doi.org/10.1007/s00125-018-4789-6] [PMID: 30593607]
[78]
Leiter LA, Teoh H, Kallend D, et al. Inclisiran Lowers LDL-C and PCSK9 irrespective of diabetes status: The ORION-1 randomized clinical trial. Diabetes Care 2019; 42(1): 173-6.
[http://dx.doi.org/10.2337/dc18-1491] [PMID: 30487231]
[79]
Wright RS, Ray KK, Raal FJ, et al. Pooled patient-level analysis of inclisiran trials in patients with familial hypercholesterolemia or atherosclerosis. J Am Coll Cardiol 2021; 77(9): 1182-93.
[http://dx.doi.org/10.1016/j.jacc.2020.12.058] [PMID: 33663735]
[80]
Hovingh GK, Lepor NE, Kallend D, Stoekenbroek RM, Wijngaard PLJ, Raal FJ. Inclisiran durably lowers low-density lipoprotein cholesterol and proprotein convertase subtilisin/kexin type 9 expression in homozygous familial hypercholesterolemia. Circulation 2020; 141(22): 1829-31.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.119.044431] [PMID: 32479195]
[81]
Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017; 376(18): 1713-22.
[http://dx.doi.org/10.1056/NEJMoa1615664] [PMID: 28304224]
[82]
O’Donoghue ML, Fazio S, Giugliano RP, et al. Lipoprotein(a), PCSK9 inhibition, and cardiovascular risk. Circulation 2019; 139(12): 1483-92.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.037184] [PMID: 30586750]
[83]
Nicholls SJ, Puri R, Anderson T, et al. Effect of evolocumab on progression of coronary disease in statin-treated patients. JAMA 2016; 316(22): 2373-84.
[http://dx.doi.org/10.1001/jama.2016.16951] [PMID: 27846344]
[84]
Leucker TM, Blaha MJ, Jones SR, et al. Effect of evolocumab on atherogenic lipoproteins during the peri- and early postinfarction period. Circulation 2020; 142(4): 419-21.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.120.046320] [PMID: 32718248]
[85]
Koskinas KC, Windecker S, Pedrazzini G, et al. Evolocumab for early reduction of LDL cholesterol levels in patients with acute coronary syndromes (EVOPACS). J Am Coll Cardiol 2019; 74(20): 2452-62.
[http://dx.doi.org/10.1016/j.jacc.2019.08.010] [PMID: 31479722]
[86]
Schwartz GG, Steg PG, Szarek M, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med 2018; 379(22): 2097-107.
[http://dx.doi.org/10.1056/NEJMoa1801174] [PMID: 30403574]
[87]
Kereiakes DJ, Robinson JG, Cannon CP, et al. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: The ODYSSEY COMBO I study. Am Heart J 2015; 169(6): 906-915.e13.
[http://dx.doi.org/10.1016/j.ahj.2015.03.004] [PMID: 26027630]
[88]
Cannon CP, Cariou B, Blom D, et al. 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(19): 1186-94.
[http://dx.doi.org/10.1093/eurheartj/ehv028] [PMID: 25687353]
[89]
Roth EM, Moriarty PM, Bergeron J, et al. A phase III randomized trial evaluating alirocumab 300 mg every 4 weeks as monotherapy or add-on to statin: ODYSSEY CHOICE I. Atherosclerosis 2016; 254: 254-62.
[http://dx.doi.org/10.1016/j.atherosclerosis.2016.08.043] [PMID: 27639753]
[90]
Bittner VA, Szarek M, Aylward PE, et al. Effect of Alirocumab on Lipoprotein(a) and cardiovascular risk after acute coronary syndrome. J Am Coll Cardiol 2020; 75(2): 133-44.
[http://dx.doi.org/10.1016/j.jacc.2019.10.057] [PMID: 31948641]
[91]
Dufour R, Hovingh GK, Guyton JR, et al. Individualized low-density lipoprotein cholesterol reduction with alirocumab titration strategy in heterozygous familial hypercholesterolemia: Results from an open-label extension of the ODYSSEY LONG TERM trial. J Clin Lipidol 2019; 13(1): 138-47.
[http://dx.doi.org/10.1016/j.jacl.2018.11.007] [PMID: 30591415]
[92]
Kastelein JJP, Ginsberg HN, Langslet G, et al. ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur Heart J 2015; 36(43): ehv370.
[http://dx.doi.org/10.1093/eurheartj/ehv370] [PMID: 26330422]
[93]
Ginsberg HN, Rader DJ, Raal FJ, et al. Efficacy and safety of alirocumab in patients with heterozygous familial hypercholesterolemia and LDL-C of 160 mg/dl or higher. Cardiovasc Drugs Ther 2016; 30(5): 473-83.
[http://dx.doi.org/10.1007/s10557-016-6685-y] [PMID: 27618825]
[94]
Leiter LA, Cariou B, Müller-Wieland D, et al. Efficacy and safety of alirocumab in insulin-treated individuals with type 1 or type 2 diabetes and high cardiovascular risk: The ODYSSEY DM-INSULIN randomized trial. Diabetes Obes Metab 2017; 19(12): 1781-92.
[http://dx.doi.org/10.1111/dom.13114] [PMID: 28905478]
[95]
Ray KK, Del Prato S, Müller-Wieland D, et al. Alirocumab therapy in individuals with type 2 diabetes mellitus and atherosclerotic cardiovascular disease: Analysis of the ODYSSEY DM-DYSLIPIDEMIA and DM-INSULIN studies. Cardiovasc Diabetol 2019; 18(1): 149.
[http://dx.doi.org/10.1186/s12933-019-0951-9] [PMID: 31706300]
[96]
Moriarty PM, Thompson PD, Cannon CP, et al. Efficacy and safety of alirocumab vs. ezetimibe in statin-intolerant patients, with a statin rechallenge arm: The ODYSSEY ALTERNATIVE randomized trial. J Clin Lipidol 2015; 9(6): 758-69.
[http://dx.doi.org/10.1016/j.jacl.2015.08.006] [PMID: 26687696]
[97]
Moriarty PM, Thompson PD, Cannon CP, et al. Efficacy and safety of alirocumab in statin-intolerant patients over 3 years: Open-label treatment period of the ODYSSEY ALTERNATIVE trial. J Clin Lipidol 2020; 14(1): 88-97.e2.
[http://dx.doi.org/10.1016/j.jacl.2020.01.001] [PMID: 32192644]
[98]
Stroes E, Guyton JR, Lepor N, et al. Efficacy and safety of alirocumab 150 mg every 4 weeks in patients with hypercholesterolemia not on statin therapy: The ODYSSEY CHOICE II study. J Am Heart Assoc 2016; 5(9): e003421.
[http://dx.doi.org/10.1161/JAHA.116.003421] [PMID: 27625344]
[99]
Trankle CR, Wohlford G, Buckley LF, et al. Alirocumab in acute myocardial infarction. J Cardiovasc Pharmacol 2019; 74(3): 266-9.
[http://dx.doi.org/10.1097/FJC.0000000000000706] [PMID: 31356537]
[100]
Ray KK, Wright RS, Kallend D, et al. Two phase 3 trials of inclisiran in patients with elevated ldl cholesterol. N Engl J Med 2020; 382(16): 1507-19.
[http://dx.doi.org/10.1056/NEJMoa1912387] [PMID: 32187462]
[101]
Nicholls SJ, Kataoka Y, Nissen SE, et al. Effect of evolocumab on coronary plaque phenotype and burden in statin-treated patients following myocardial infarction. JACC Cardiovasc Imaging 2022; 15(7): 1308-21.
[http://dx.doi.org/10.1016/j.jcmg.2022.03.002] [PMID: 35431172]
[102]
Montone RA, Niccoli G, Crea F, Jang IK. Management of non-culprit coronary plaques in patients with acute coronary syndrome. Eur Heart J 2020; 41(37): 3579-86.
[http://dx.doi.org/10.1093/eurheartj/ehaa481] [PMID: 32676644]
[103]
Maulucci G, Cipriani F, Russo D, et al. Improved endothelial function after short-term therapy with evolocumab. J Clin Lipidol 2018; 12(3): 669-73.
[http://dx.doi.org/10.1016/j.jacl.2018.02.004] [PMID: 29544724]
[104]
Leucker TM, Gerstenblith G, Schär M, et al. Evolocumab, a PCSK9-monoclonal antibody, rapidly reverses coronary artery endothelial dysfunction in people living with HIV and people with dyslipidemia. J Am Heart Assoc 2020; 9(14): e016263.
[http://dx.doi.org/10.1161/JAHA.120.016263] [PMID: 32674634]
[105]
Otake H, Sugizaki Y, Toba T, et al. Efficacy of alirocumab for reducing plaque vulnerability: Study protocol for ALTAIR, a randomized controlled trial in Japanese patients with coronary artery disease receiving rosuvastatin. J Cardiol 2019; 73(3): 228-32.
[http://dx.doi.org/10.1016/j.jjcc.2018.11.012] [PMID: 30579806]
[106]
Sugizaki Y, Otake H, Kawamori H, et al. Adding alirocumab to rosuvastatin helps reduce the vulnerability of thin-cap fibroatheroma. JACC Cardiovasc Imaging 2020; 13(6): 1452-4.
[http://dx.doi.org/10.1016/j.jcmg.2020.01.021] [PMID: 32199850]
[107]
Räber L, Ueki Y, Otsuka T, et al. Effect of alirocumab added to high-intensity statin therapy on coronary atherosclerosis in patients with acute myocardial infarction. JAMA 2022; 327(18): 1771-81.
[http://dx.doi.org/10.1001/jama.2022.5218] [PMID: 35368058]
[108]
Ako J, Hibi K, Tsujita K, et al. Effect of alirocumab on coronary atheroma volume in japanese patients with acute coronary syndrome - The ODYSSEY J-IVUS Trial-. Circ J 2019; 83(10): 2025-33.
[http://dx.doi.org/10.1253/circj.CJ-19-0412] [PMID: 31434809]
[109]
Metzner T, Leitner DR, Dimsity G, et al. Short-term treatment with alirocumab, flow-dependent dilatation of the brachial artery and use of magnetic resonance diffusion tensor imaging to evaluate vascular structure: An exploratory pilot study. Biomedicines 2022; 10(1): 152.
[http://dx.doi.org/10.3390/biomedicines10010152] [PMID: 35052831]
[110]
Burggraaf B, Pouw NMC, Arroyo SF, et al. A placebo-controlled proof-of-concept study of alirocumab on postprandial lipids and vascular elasticity in insulin-treated patients with type 2 diabetes mellitus. Diabetes Obes Metab 2020; 22(5): 807-16.
[http://dx.doi.org/10.1111/dom.13960] [PMID: 31912632]
[111]
Vlachopoulos C, Koutagiar I, Skoumas I, et al. Long-term administration of proprotein convertase subtilisin/kexin type 9 inhibitors reduces arterial FDG uptake. JACC Cardiovasc Imaging 2019; 12(12): 2573-4.
[http://dx.doi.org/10.1016/j.jcmg.2019.09.024] [PMID: 31806185]
[112]
Hoogeveen RM, Opstal TSJ, Kaiser Y, et al. PCSK9 antibody alirocumab attenuates arterial wall inflammation without changes in circulating inflammatory markers. JACC Cardiovasc Imaging 2019; 12(12): 2571-3.
[http://dx.doi.org/10.1016/j.jcmg.2019.06.022] [PMID: 31422119]
[113]
Yang W, Cai X, Lin C, et al. Reduction of C-reactive protein, low-density lipoprotein cholesterol, and its relationship with cardiovascular events of different lipid-lowering therapies: A systematic review and meta-analysis of randomized controlled trials. Medicine 2022; 101(37): e30563.
[http://dx.doi.org/10.1097/MD.0000000000030563] [PMID: 36123891]
[114]
Cao YX, Li S, Liu HH, Li JJ. Impact of PCSK9 monoclonal antibodies on circulating hs-CRP levels: A systematic review and meta-analysis of randomised controlled trials. BMJ Open 2018; 8(9): e022348.
[http://dx.doi.org/10.1136/bmjopen-2018-022348] [PMID: 30287608]
[115]
Bernelot Moens SJ, Neele AE, Kroon J, et al. PCSK9 monoclonal antibodies reverse the pro-inflammatory profile of monocytes in familial hypercholesterolaemia. Eur Heart J 2017; 38(20): 1584-93.
[http://dx.doi.org/10.1093/eurheartj/ehx002] [PMID: 28329114]
[116]
Scicali R, Mandraffino G, Scuruchi M, et al. Effects of lipid lowering therapy optimization by PCSK9 inhibitors on circulating CD34+ cells and pulse wave velocity in familial hypercholesterolemia subjects without atherosclerotic cardiovascular disease: Realworld data from two lipid units. Biomedicines 2022; 10(7): 1715.
[http://dx.doi.org/10.3390/biomedicines10071715] [PMID: 35885020]
[117]
Scicali R, Mandraffino G, Di Pino A, et al. Impact of high neutrophil-to-lymphocyte ratio on the cardiovascular benefit of PCSK9 inhibitors in familial hypercholesterolemia subjects with atherosclerotic cardiovascular disease: Real-world data from two lipid units. Nutr Metab Cardiovasc Dis 2021; 31(12): 3401-6.
[http://dx.doi.org/10.1016/j.numecd.2021.08.034] [PMID: 34627693]
[118]
Giugliano RP, Pedersen TR, Park JG, et al. Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: A prespecified secondary analysis of the FOURIER trial. Lancet 2017; 390(10106): 1962-71.
[http://dx.doi.org/10.1016/S0140-6736(17)32290-0] [PMID: 28859947]
[119]
Gencer B, Mach F, Murphy SA, et al. Efficacy of evolocumab on cardiovascular outcomes in patients with recent myocardial infarction. JAMA Cardiol 2020; 5(8): 952-7.
[http://dx.doi.org/10.1001/jamacardio.2020.0882] [PMID: 32432684]
[120]
Sabatine MS, De Ferrari GM, Giugliano RP, et al. Clinical benefit of evolocumab by severity and extent of coronary artery disease. Circulation 2018; 138(8): 756-66.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.034309] [PMID: 29626068]
[121]
Bohula EA, Giugliano RP, Leiter LA, et al. Inflammatory and cholesterol risk in the FOURIER trial. Circulation 2018; 138(2): 131-40.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.034032] [PMID: 29530884]
[122]
Deedwania P, Murphy SA, Scheen A, et al. Efficacy and safety of PCSK9 inhibition with evolocumab in reducing cardiovascular events in patients with metabolic syndrome receiving statin therapy. JAMA Cardiol 2021; 6(2): 139-47.
[http://dx.doi.org/10.1001/jamacardio.2020.3151] [PMID: 32785614]
[123]
Giugliano RP, Pedersen TR, Saver JL, et al. Stroke prevention with the PCSK9 (Proprotein convertase subtilisin-kexin type 9) inhibitor evolocumab added to statin in high-risk patients with stable atherosclerosis. Stroke 2020; 51(5): 1546-54.
[http://dx.doi.org/10.1161/STROKEAHA.119.027759] [PMID: 32312223]
[124]
Bonaca MP, Nault P, Giugliano RP, et al. Lowdensity lipoprotein cholesterol lowering with evolocumab and outcomes in patients with peripheral artery disease. Circulation 2018; 137(4): 338-50.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.117.032235] [PMID: 29133605]
[125]
Erviti J, Wright J, Bassett K, et al. Restoring mortality data in the FOURIER cardiovascular outcomes trial of evolocumab in patients with cardiovascular disease: A reanalysis based on regulatory data. BMJ Open 2022; 12(12): e060172.
[http://dx.doi.org/10.1136/bmjopen-2021-060172] [PMID: 36585131]
[126]
Steg PG, Szarek M, Bhatt DL, et al. Effect of Alirocumab on mortality after acute coronary syndromes. Circulation 2019; 140(2): 103-12.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.038840] [PMID: 31117810]
[127]
Schwartz GG, Gabriel Steg P, Bhatt DL, et al. Clinical efficacy and safety of alirocumab after acute coronary syndrome according to achieved level of low-density lipoprotein cholesterol. Circulation 2021; 143(11): 1109-22.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.120.049447] [PMID: 33438437]
[128]
Jukema JW, Szarek M, Zijlstra LE, et al. Alirocumab in patients with polyvascular disease and recent acute coronary syndrome. J Am Coll Cardiol 2019; 74(9): 1167-76.
[http://dx.doi.org/10.1016/j.jacc.2019.03.013] [PMID: 30898609]
[129]
Goodman SG, Aylward PE, Szarek M, et al. Effects of alirocumab on cardiovascular events after coronary bypass surgery. J Am Coll Cardiol 2019; 74(9): 1177-86.
[http://dx.doi.org/10.1016/j.jacc.2019.07.015] [PMID: 31466614]
[130]
Tuñón J, Steg PG, Bhatt DL, et al. Effect of alirocumab on major adverse cardiovascular events according to renal function in patients with a recent acute coronary syndrome: Prespecified analysis from the ODYSSEY OUTCOMES randomized clinical trial. Eur Heart J 2020; 41(42): 4114-23.
[http://dx.doi.org/10.1093/eurheartj/ehaa498] [PMID: 32820320]
[131]
Schwartz GG, Szarek M, Bittner VA, et al. Lipoprotein(a) and benefit of PCSK9 inhibition in patients with nominally controlled LDL cholesterol. J Am Coll Cardiol 2021; 78(5): 421-33.
[http://dx.doi.org/10.1016/j.jacc.2021.04.102] [PMID: 34325831]
[132]
Jukema JW, Zijlstra LE, Bhatt DL, et al. Effect of alirocumab on stroke in ODYSSEY OUTCOMES. Circulation 2019; 140(25): 2054-62.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.119.043826] [PMID: 31707788]
[133]
Schwartz GG, Steg PG, Szarek M, et al. Peripheral artery disease and venous thromboembolic events after acute coronary syndrome. Circulation 2020; 141(20): 1608-17.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.120.046524] [PMID: 32223446]
[134]
Marston NA, Gurmu Y, Melloni GEM, et al. The effect of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) inhibition on the risk of venous thromboembolism. Circulation 2020; 141(20): 1600-7.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.120.046397] [PMID: 32223429]
[135]
Marston NA, Kamanu FK, Nordio F, et al. Predicting benefit from evolocumab therapy in patients with atherosclerotic disease using a genetic risk score. Circulation 2020; 141(8): 616-23.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.119.043805] [PMID: 31707849]
[136]
Damask A, Steg PG, Schwartz GG, et al. Patients with high genome-wide polygenic risk scores for coronary artery disease may receive greater clinical benefit from alirocumab treatment in the ODYSSEY OUTCOMES trial. Circulation 2020; 141(8): 624-36.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.119.044434] [PMID: 31707832]
[137]
Baigent C, Blackwell L, Emberson J, 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(9753): 1670-81.
[http://dx.doi.org/10.1016/S0140-6736(10)61350-5] [PMID: 21067804]
[138]
Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015; 372(25): 2387-97.
[http://dx.doi.org/10.1056/NEJMoa1410489] [PMID: 26039521]
[139]
O’Donoghue ML, Giugliano RP, Wiviott SD, et al. Long-term evolocumab in patients with established atherosclerotic cardiovascular disease. Circulation 2022; 146(15): 1109-19.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.122.061620] [PMID: 36031810]
[140]
Ridker PM, Revkin J, Amarenco P, et al. Cardiovascular efficacy and safety of bococizumab in high-risk patients. N Engl J Med 2017; 376(16): 1527-39.
[http://dx.doi.org/10.1056/NEJMoa1701488] [PMID: 28304242]
[141]
Zhang XL, Zhu QQ, Zhu L, et al. Safety and efficacy of anti-PCSK9 antibodies: A meta-analysis of 25 randomized, controlled trials. BMC Med 2015; 13(1): 123.
[http://dx.doi.org/10.1186/s12916-015-0358-8] [PMID: 26099511]
[142]
Robinson JG, Farnier M, Krempf M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med 2015; 372(16): 1489-99.
[http://dx.doi.org/10.1056/NEJMoa1501031] [PMID: 25773378]
[143]
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(13): 1278-88.
[http://dx.doi.org/10.1016/j.jacc.2014.01.006] [PMID: 24509273]
[144]
Giugliano RP, Mach F, Zavitz K, et al. Cognitive function in a randomized trial of evolocumab. N Engl J Med 2017; 377(7): 633-43.
[http://dx.doi.org/10.1056/NEJMoa1701131] [PMID: 28813214]
[145]
Kaddoura R, Orabi B, Salam AM. Efficacy and safety of PCSK9 monoclonal antibodies: An evidence-based review and update. J Drug Assess 2020; 9(1): 129-44.
[http://dx.doi.org/10.1080/21556660.2020.1801452] [PMID: 32939318]
[146]
Colhoun HM, Ginsberg HN, Robinson JG, et al. No effect of PCSK9 inhibitor alirocumab on the incidence of diabetes in a pooled analysis from 10 ODYSSEY Phase 3 studies. Eur Heart J 2016; 37(39): 2981-9.
[http://dx.doi.org/10.1093/eurheartj/ehw292] [PMID: 27460890]
[147]
Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol. J Am Coll Cardiol 2019; 73(24): e285-350.
[http://dx.doi.org/10.1016/j.jacc.2018.11.003] [PMID: 30423393]
[148]
Fonarow GC, van Hout B, Villa G, Arellano J, Lindgren P. Updated cost-effectiveness analysis of evolocumab in patients with very high-risk atherosclerotic cardiovascular disease. JAMA Cardiol 2019; 4(7): 691-5.
[http://dx.doi.org/10.1001/jamacardio.2019.1647] [PMID: 31166576]
[149]
Kazi DS, Penko J, Coxson PG, Guzman D, Wei PC, Bibbins-Domingo K. Cost-effectiveness of alirocumab. Ann Intern Med 2019; 170(4): 221-9.
[http://dx.doi.org/10.7326/M18-1776] [PMID: 30597485]
[150]
Bhatt DL, Briggs AH, Reed SD, et al. Cost-effectiveness of alirocumab in patients with acute coronary syndromes. J Am Coll Cardiol 2020; 75(18): 2297-308.
[http://dx.doi.org/10.1016/j.jacc.2020.03.029] [PMID: 32381160]
[151]
Desai NR, Campbell C, Electricwala B, et al. Cost effectiveness of inclisiran in atherosclerotic cardiovascular patients with elevated low-density lipoprotein cholesterol despite statin use: A threshold analysis. Am J Cardiovasc Drugs 2022; 22(5): 545-56.
[http://dx.doi.org/10.1007/s40256-022-00534-9] [PMID: 35595929]
[152]
Mullard A. Merck readies oral, macrocyclic PCSK9 inhibitor for phase II test. Nat Rev Drug Discov 2022; 21(1): 9.
[http://dx.doi.org/10.1038/d41573-021-00195-4] [PMID: 34795405]

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