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

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). A pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients w...

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Autores: Bittner, Vera A., Szarek, Michael|||0000-0002-0046-0264, Aylward, Philip|||0000-0002-5358-8552, Bhatt, Deepak L.|||0000-0002-1278-6245, Diaz, Rafael, Edelberg, Jay M., Fras, Zlatko, Goodman, Shaun G., Halvorsen, Sigrun, Hanotin, Corinne|||0000-0002-9396-3126, Harrington, Robert A., Jukema, J. Wouter|||0000-0002-3246-8359, Loizeau, Virginie, Moriarty, Patrick Maurice, Moryusef, Angèle, Pordy, Robert, Roe, Matthew T., Sinnaeve, Peter|||0000-0003-4716-5892, Tsimikas, Sotirios|||0000-0001-9834-9494, Vogel, Robert A., White, Harvey D., Zahger, Doron, Zeiher, Andreas Michael|||0000-0003-1711-5819, Steg, Philippe Gabriel|||0000-0001-6896-2941, Schwartz, Gregory G., Matas Pericas, Laia, Gusi Tragant, Gabriel, Coca Payeras, Antonio, Cequier, Ángel|||0000-0002-3230-0011, García-Dorado, David|||0000-0002-1126-1279, Bruguera Cortada, Jordi
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:283349
Acceso en línea:https://ddd.uab.cat/record/283349
https://dx.doi.org/urn:doi:10.1016/j.jacc.2019.10.057
Access Level:acceso abierto
Palabra clave:Acute coronary syndromes
Alirocumab
Low-density lipoprotein cholesterol
Major adverse cardiovascular events
Proprotein convertase subtilisin/kexin type 9 inhibition
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spelling Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary SyndromeBittner, Vera A.Szarek, Michael|||0000-0002-0046-0264Aylward, Philip|||0000-0002-5358-8552Bhatt, Deepak L.|||0000-0002-1278-6245Diaz, RafaelEdelberg, Jay M.Fras, ZlatkoGoodman, Shaun G.Halvorsen, SigrunHanotin, Corinne|||0000-0002-9396-3126Harrington, Robert A.Jukema, J. Wouter|||0000-0002-3246-8359Loizeau, VirginieMoriarty, Patrick MauriceMoryusef, AngèlePordy, RobertRoe, Matthew T.Sinnaeve, Peter|||0000-0003-4716-5892Tsimikas, Sotirios|||0000-0001-9834-9494Vogel, Robert A.White, Harvey D.Zahger, DoronZeiher, Andreas Michael|||0000-0003-1711-5819Steg, Philippe Gabriel|||0000-0001-6896-2941Schwartz, Gregory G.Matas Pericas, LaiaGusi Tragant, GabrielCoca Payeras, AntonioCequier, Ángel|||0000-0002-3230-0011García-Dorado, David|||0000-0002-1126-1279Bruguera Cortada, JordiAcute coronary syndromesAlirocumabLow-density lipoprotein cholesterolMajor adverse cardiovascular eventsProprotein convertase subtilisin/kexin type 9 inhibitionLipoprotein(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). 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). 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. 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). 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).Universitat Autònoma de Barcelona 22020-01-0120202020-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/283349https://dx.doi.org/urn:doi:10.1016/j.jacc.2019.10.057reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2833492026-06-06T12:50:31Z
dc.title.none.fl_str_mv Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome
title Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome
spellingShingle Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome
Bittner, Vera A.
Acute coronary syndromes
Alirocumab
Low-density lipoprotein cholesterol
Major adverse cardiovascular events
Proprotein convertase subtilisin/kexin type 9 inhibition
title_short Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome
title_full Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome
title_fullStr Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome
title_full_unstemmed Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome
title_sort Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome
dc.creator.none.fl_str_mv Bittner, Vera A.
Szarek, Michael|||0000-0002-0046-0264
Aylward, Philip|||0000-0002-5358-8552
Bhatt, Deepak L.|||0000-0002-1278-6245
Diaz, Rafael
Edelberg, Jay M.
Fras, Zlatko
Goodman, Shaun G.
Halvorsen, Sigrun
Hanotin, Corinne|||0000-0002-9396-3126
Harrington, Robert A.
Jukema, J. Wouter|||0000-0002-3246-8359
Loizeau, Virginie
Moriarty, Patrick Maurice
Moryusef, Angèle
Pordy, Robert
Roe, Matthew T.
Sinnaeve, Peter|||0000-0003-4716-5892
Tsimikas, Sotirios|||0000-0001-9834-9494
Vogel, Robert A.
White, Harvey D.
Zahger, Doron
Zeiher, Andreas Michael|||0000-0003-1711-5819
Steg, Philippe Gabriel|||0000-0001-6896-2941
Schwartz, Gregory G.
Matas Pericas, Laia
Gusi Tragant, Gabriel
Coca Payeras, Antonio
Cequier, Ángel|||0000-0002-3230-0011
García-Dorado, David|||0000-0002-1126-1279
Bruguera Cortada, Jordi
author Bittner, Vera A.
author_facet Bittner, Vera A.
Szarek, Michael|||0000-0002-0046-0264
Aylward, Philip|||0000-0002-5358-8552
Bhatt, Deepak L.|||0000-0002-1278-6245
Diaz, Rafael
Edelberg, Jay M.
Fras, Zlatko
Goodman, Shaun G.
Halvorsen, Sigrun
Hanotin, Corinne|||0000-0002-9396-3126
Harrington, Robert A.
Jukema, J. Wouter|||0000-0002-3246-8359
Loizeau, Virginie
Moriarty, Patrick Maurice
Moryusef, Angèle
Pordy, Robert
Roe, Matthew T.
Sinnaeve, Peter|||0000-0003-4716-5892
Tsimikas, Sotirios|||0000-0001-9834-9494
Vogel, Robert A.
White, Harvey D.
Zahger, Doron
Zeiher, Andreas Michael|||0000-0003-1711-5819
Steg, Philippe Gabriel|||0000-0001-6896-2941
Schwartz, Gregory G.
Matas Pericas, Laia
Gusi Tragant, Gabriel
Coca Payeras, Antonio
Cequier, Ángel|||0000-0002-3230-0011
García-Dorado, David|||0000-0002-1126-1279
Bruguera Cortada, Jordi
author_role author
author2 Szarek, Michael|||0000-0002-0046-0264
Aylward, Philip|||0000-0002-5358-8552
Bhatt, Deepak L.|||0000-0002-1278-6245
Diaz, Rafael
Edelberg, Jay M.
Fras, Zlatko
Goodman, Shaun G.
Halvorsen, Sigrun
Hanotin, Corinne|||0000-0002-9396-3126
Harrington, Robert A.
Jukema, J. Wouter|||0000-0002-3246-8359
Loizeau, Virginie
Moriarty, Patrick Maurice
Moryusef, Angèle
Pordy, Robert
Roe, Matthew T.
Sinnaeve, Peter|||0000-0003-4716-5892
Tsimikas, Sotirios|||0000-0001-9834-9494
Vogel, Robert A.
White, Harvey D.
Zahger, Doron
Zeiher, Andreas Michael|||0000-0003-1711-5819
Steg, Philippe Gabriel|||0000-0001-6896-2941
Schwartz, Gregory G.
Matas Pericas, Laia
Gusi Tragant, Gabriel
Coca Payeras, Antonio
Cequier, Ángel|||0000-0002-3230-0011
García-Dorado, David|||0000-0002-1126-1279
Bruguera Cortada, Jordi
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv Acute coronary syndromes
Alirocumab
Low-density lipoprotein cholesterol
Major adverse cardiovascular events
Proprotein convertase subtilisin/kexin type 9 inhibition
topic Acute coronary syndromes
Alirocumab
Low-density lipoprotein cholesterol
Major adverse cardiovascular events
Proprotein convertase subtilisin/kexin type 9 inhibition
description 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). 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). 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. 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). 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).
publishDate 2020
dc.date.none.fl_str_mv 2
2020-01-01
2020
2020-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/283349
https://dx.doi.org/urn:doi:10.1016/j.jacc.2019.10.057
url https://ddd.uab.cat/record/283349
https://dx.doi.org/urn:doi:10.1016/j.jacc.2019.10.057
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
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