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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Detalles Bibliográficos
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
Descripción
Sumario: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).

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