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Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome

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Bittner, Vera A.Szarek, MichaelAylward, Philip E.Bhatt, Deepak L.Diaz, RafaelEdelberg, Jay M.Fras, ZlatkoGoodman, Shaun G.Halvorsen, SigrunHanotin, CorinneHarrington, Robert A.Jukema, J. WouterLoizeau, VirginieMoriarty, Patrick M.Moryusef, AngelePordy, RobertRoe, Matthew T.Sinnaeve, PeterTsimikas, SotiriosVogel, RobertWhite, Harvey D.Zahger, DoronZeiher, Andreas M.Steg, GabrielSchwartz, Gregory G.Aylward, Philip E.Drexel, HeinzSinnaeve, PeterDilic, MirzaLopes, Renato D.Gotcheva, Nina N.Goodman, Shaun G.Prieto, Juan-CarlosYong, HuoLopez-Jaramillo, PatricioPecin, IvanReiner, ZeljkoOstadal, PetrPoulsen, Steen HvitfeldtViigimaa, MargusNieminen, Markku S.Danchin, NicolasChumburidze, VakhtangMarx, NikolausLiberopoulos, EvangelosMontenegro Valdovinos, Pablo CarlosTse, Hung-FatKiss, Robert GaborXavier, DenisZahger, DoronValgimigli, MarcoKimura, TakeshiKim, Hyo SooKim, Sang-HyunErglis, AndrejsLaucevicius, AleksandrasKedev, SaskoYusoff, KhalidRamos Lopez, Gabriel ArturoAlings, MarcoHalvorsen, SigrunCorrea Flores, Roger M.Sy, Rody G.Budaj, AndrzejMorais, JoaoDorobantu, MariaKarpov, YuriRistic, Arsen D.Chua, TerranceMurin, JanFras, ZlatkoDalby, Anthony J.Tunon, Josede Silva, H. AsitaHagstrom, EmilMuller, ChristianChiang, Chern-EnSritara, PiyamitrGuneri, SemaParkhomenko, AlexanderRay, Kausik K.Moriarty, Patrick M.Vogel, RobertChaitman, BernardKelsey, Sheryl F.Olsson, Anders G.Rouleau, Jean-LucienSimoons, Maarten L.Alexander, KarenMeloni, ChiaraRosenson, RobertSijbrands, Eric J. G.Alexander, John H.Armaganijan, LucianaBagai, AkshayBahit, Maria CeciliaBrennan, J. MatthewClifton, ShaunDeVore, Adam D.Deloatch, ShalondaDickey, SheilaDombrowski, KeithDucrocq, GregoryEapen, ZubinEndsley, PatriciaEppinger, ArleenHess, Connie NgHlatky, Mark A.Jordan, Joseph DedrickKnowles, Joshua W.Kolls, Bradley J.Kong, David F.Leonardi, SergioLillis, LindaLopes, Renato D.Maron, David J.Marcus, JillMathews, RobinMehta, Rajendra H.Mentz, Robert J.Moreira, Humberto GranerPatel, Chetan B.Pereira, Sabrina BernardezPerkins, LynnPovsic, Thomas J.Puymirat, EtienneJones, William SchuylerShah, Bimal R.Sherwood, Matthew W.Stringfellow, KenyaSujjavanich, DarinToma, MustafaTrotter, Charlenevan Diepen, Sean F. P.Wilson, Matthew D.Yan, Andrew Tze-KaySchiavi, Lilia B.Garrido, MarceloAlvarisqueta, Andres F.Sassone, Sonia A.Bordonava, Anselmo P.Alves De Lima, Alberto E.Schmidberg, Jorge M.Duronto, Ernesto A.Caruso, Orlando C.Novaretto, Leonardo P.Angel Hominal, MiguelMontana, Oscar R.Caccavo, AlbertoGomez Vilamajo, Oscar A.Lorenzatti, Alberto J.Cartasegna, Luis R.Paterlini, Gustavo A.Mackinnon, Ignacio J.Caime, Guillermo D.Amuchastegui, MarcosCodutti, Oscar R.Jure, Horacio O.Bono, Julio O. E.Hrabar, Adrian D.Vallejos, Julio A.Ahuad Guerrero, Rodolfo A.Novoa, FedericoPatocchi, Cristian A.Zaidman, Cesar J.Giuliano, Maria E.Dran, Ricardo D.Vico, Marisa L.Carnero, Gabriela S.Guzman, Pablo N.Medrano Allende, Juan C.Garcia Brasca, Daniela F.Bustamante Labarta, Miguel H.Nani, SebastianBlumberg, Eduardo D. S.Colombo, Hugo R.Liberman, AlbertoLuciardi, Hector L.Waisman, Gabriel D.Berli, Mario A.Garcia Duran, Ruben O.Cestari, Horacio G.Luquez, Hugo A.Giordano, Jorge A.Saavedra, Silvia S.Waites, Jonathon H.Collins, NicholasSoward, AllanHii, Chris L. S.Shaw, JamesArstall, Margaret A.Horowitz, JohnRogers, James F.Colquhoun, DavidFlores, Romulo E. OqueliRoberts-Thomson, PhilipRaffel, OwenLehman, Sam J.Coverdale, Steven G. M.Garrahy, Paul J.Starmer, GregorySader, MarkCarroll, Patrick A.Zweiker, RobertHoppe, UtaHuber, KurtBerger, RudolfWeidinger, FranzFaes, DirkHermans, KurtPirenne, BrunoLeone, AttilioHoffer, EtienneVrolix, Mathias C. 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Issue Date
Jan-2020
Publisher
Elsevier BV
Keywords
acute coronary syndromes; alirocumab; low-density lipoprotein cholesterol; major adverse cardiovascular events; proprotein convertase subtilisin/kexin type 9 inhibition
Citation
Journal of the American College of Cardiology, v.75, no.2, pp 133 - 144
Pages
12
Indexed
SCIE
SCOPUS
Journal Title
Journal of the American College of Cardiology
Volume
75
Number
2
Start Page
133
End Page
144
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/62904
DOI
10.1016/j.jacc.2019.10.057
ISSN
0735-1097
1558-3597
Abstract
Background Lipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C). Objectives A pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients with recent acute coronary syndrome (ACS) determined whether alirocumab-induced changes in lipoprotein(a) and LDL-C independently predicted major adverse cardiovascular events (MACE). Methods One to 12 months after ACS, 18,924 patients on high-intensity statin therapy were randomized to alirocumab or placebo and followed for 2.8 years (median). Lipoprotein(a) was measured at randomization and 4 and 12 months thereafter. The primary MACE outcome was coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina. Results Baseline lipoprotein(a) levels (median: 21.2 mg/dl; interquartile range [IQR]: 6.7 to 59.6 mg/dl) and LDL-C [corrected for cholesterol content in lipoprotein(a)] predicted MACE. Alirocumab reduced lipoprotein(a) by 5.0 mg/dl (IQR: 0 to 13.5 mg/dl), corrected LDL-C by 51.1 mg/dl (IQR: 33.7 to 67.2 mg/dl), and reduced the risk of MACE (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.78 to 0.93). Alirocumab-induced reductions of lipoprotein(a) and corrected LDL-C independently predicted lower risk of MACE, after adjustment for baseline concentrations of both lipoproteins and demographic and clinical characteristics. A 1-mg/dl reduction in lipoprotein(a) with alirocumab was associated with a HR of 0.994 (95% CI: 0.990 to 0.999; p = 0.0081). Conclusions Baseline lipoprotein(a) and corrected LDL-C levels and their reductions by alirocumab predicted the risk of MACE after recent ACS. Lipoprotein(a) lowering by alirocumab is an independent contributor to MACE reduction, which suggests that lipoprotein(a) should be an independent treatment target after ACS. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402)
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Guro Hospital (Department of Cardiology, Guro Hospital)
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