Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol

Gregory G. Schwartz; Michael Szarek; Vera A. Bittner; Rafael Diaz; Shaun G. Goodman; J. Wouter Jukema; Ulf Landmesser; Patricio López-Jaramillo; Garen Manvelian; Robert Pordy; Michel Scemama; Peter Sinnaeve; Harvey D. White; Ph Gabriel Steg; ODYSSEY OUTCOMES Committees and Investigators; Philip E. Aylward; Sam J. Lehman

doi:10.1016/j.jacc.2021.04.102

Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol

Gregory G. Schwartz, Michael Szarek, Vera A. Bittner, Rafael Diaz, Shaun G. Goodman, J. Wouter Jukema, Ulf Landmesser, Patricio López-Jaramillo, Garen Manvelian, Robert Pordy, Michel Scemama, Peter Sinnaeve, Harvey D. White, Ph Gabriel Steg, ODYSSEY OUTCOMES Committees and Investigators, Philip E. Aylward, Sam J. Lehman

College of Medicine and Public Health

Research output: Contribution to journal › Article › peer-review

79 Citations (Scopus)

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Abstract

Background: Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. Objectives: In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. Methods: ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL (median 69.4 mg/dL; interquartile range: 64.3-74.0 mg/dL); in 14,573 patients (77.0%), both determinations were ≥70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2-111.0 mg/dL). Results: In the lower LDL-C subgroup, MACE rates were 4.2 and 3.1 per 100 patient-years among placebo-treated patients with baseline lipoprotein(a) greater than or less than or equal to the median (13.7 mg/dL). Corresponding adjusted treatment hazard ratios were 0.68 (95% confidence interval [CI]: 0.52-0.90) and 1.11 (95% CI: 0.83-1.49), with treatment-lipoprotein(a) interaction on MACE (P_interaction = 0.017). In the higher LDL-C subgroup, MACE rates were 4.7 and 3.8 per 100 patient-years among placebo-treated patients with lipoprotein(a) >13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with P_interaction = 0.43. Conclusions: In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402)

Original language	English
Pages (from-to)	421-433
Number of pages	13
Journal	Journal of The American College of Cardiology
Volume	78
Issue number	5
DOIs	https://doi.org/10.1016/j.jacc.2021.04.102
Publication status	Published - 3 Aug 2021

Keywords

acute coronary syndrome
lipoprotein(a)
low-density lipoprotein cholesterol
PCSK9 inhibitor

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Schwartz, G. G., Szarek, M., Bittner, V. A., Diaz, R., Goodman, S. G., Jukema, J. W., Landmesser, U., López-Jaramillo, P., Manvelian, G., Pordy, R., Scemama, M., Sinnaeve, P., White, H. D., Gabriel Steg, P., ODYSSEY OUTCOMES Committees and Investigators, Aylward, P. E., & Lehman, S. J. (2021). Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol. Journal of The American College of Cardiology, 78(5), 421-433. https://doi.org/10.1016/j.jacc.2021.04.102

@article{d9a1a940808142b79099e626d59c1642,

title = "Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol",

abstract = "Background: Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. Objectives: In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. Methods: ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL (median 69.4 mg/dL; interquartile range: 64.3-74.0 mg/dL); in 14,573 patients (77.0%), both determinations were ≥70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2-111.0 mg/dL). Results: In the lower LDL-C subgroup, MACE rates were 4.2 and 3.1 per 100 patient-years among placebo-treated patients with baseline lipoprotein(a) greater than or less than or equal to the median (13.7 mg/dL). Corresponding adjusted treatment hazard ratios were 0.68 (95% confidence interval [CI]: 0.52-0.90) and 1.11 (95% CI: 0.83-1.49), with treatment-lipoprotein(a) interaction on MACE (Pinteraction = 0.017). In the higher LDL-C subgroup, MACE rates were 4.7 and 3.8 per 100 patient-years among placebo-treated patients with lipoprotein(a) >13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with Pinteraction = 0.43. Conclusions: In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402)",

keywords = "acute coronary syndrome, lipoprotein(a), low-density lipoprotein cholesterol, PCSK9 inhibitor",

author = "Schwartz, {Gregory G.} and Michael Szarek and Bittner, {Vera A.} and Rafael Diaz and Goodman, {Shaun G.} and Jukema, {J. Wouter} and Ulf Landmesser and Patricio L{\'o}pez-Jaramillo and Garen Manvelian and Robert Pordy and Michel Scemama and Peter Sinnaeve and White, {Harvey D.} and {Gabriel Steg}, Ph and {ODYSSEY OUTCOMES Committees and Investigators} and Bhatt, {Deepak L.} and Harrington, {Robert A.} and Zeiher, {Andreas M.} and Pierluigi Tricoci and Roe, {Matthew T.} and Mahaffey, {Kenneth W.} and Edelberg, {Jay M.} and Corinne Hanotin and Guillaume Lecorps and Ang{\`e}le Moryusef and Sasiela, {William J.} and Tamby, {Jean Fran{\c c}ois} and Aylward, {Philip E.} and Heinz Drexel and Mirza Dilic and Lopes, {Renato D.} and Gotcheva, {Nina N.} and Prieto, {Juan Carlos} and Huo Yong and Ivan Pe{\'c}in and Zeljko Reiner and Petr Ostadal and Poulsen, {Steen Hvitfeldt} and Margus Viigimaa and Nieminen, {Markku S.} and Nicolas Danchin and Vakhtang Chumburidze and Nikolaus Marx and Evangelos Liberopoulos and {Montenegro Valdovinos}, {Pablo Carlos} and Tse, {Hung Fat} and Kiss, {Robert Gabor} and Denis Xavier and Doron Zahger and Marco Valgimigli and Takeshi Kimura and Kim, {Hyo Soo} and Kim, {Sang Hyun} and Andrejs Erglis and Aleksandras Laucevicius and Sasko Kedev and Khalid Yusoff and {Ramos L{\'o}pez}, {Gabriel Arturo} and Marco Alings and Sigrun Halvorsen and {Correa Flores}, {Roger M.} and Sy, {Rody G.} and Andrzej Budaj and Joao Morais and Maria Dorobantu and Yuri Karpov and Ristic, {Arsen D.} and Terrance Chua and Jan Murin and Zlatko Fras and Dalby, {Anthony J.} and Jos{\'e} Tu{\~n}{\'o}n and {Asita de Silva}, H. and Emil Hagstr{\"o}m and Christian M{\"u}ller and Chiang, {Chern En} and Piyamitr Sritara and Sema Guneri and Alexander Parkhomenko and Ray, {Kausik K.} and Moriarty, {Patrick M.} and Robert Vogel and Bernard Chaitman and Kelsey, {Sheryl F.} and Olsson, {Anders G.} and Rouleau, {Jean Lucien} and Simoons, {Maarten L.} and Karen Alexander and Chiara Meloni and Robert Rosenson and Sijbrands, {Eric J.G.} and Alexander, {John H.} and Luciana Armaganijan and Akshay Bagai and Bahit, {Maria Cecilia} and Brennan, {J. Matthew} and Shaun Clifton and DeVore, {Adam D.} and Shalonda Deloatch and Sheila Dickey and Keith Dombrowski and Gr{\'e}gory Ducrocq and Zubin Eapen and Patricia Endsley and Arleen Eppinger and Harrison, {Robert W.} and Hess, {Connie Ng} and Hlatky, {Mark A.} and Jordan, {Joseph Dedrick} and Knowles, {Joshua W.} and Kolls, {Bradley J.} and Kong, {David F.} and Sergio Leonardi and Linda Lillis and Maron, {David J.} and Jill Marcus and Robin Mathews and Mehta, {Rajendra H.} and Mentz, {Robert J.} and Moreira, {Humberto Graner} and Patel, {Chetan B.} and Pereira, {Sabrina Bernardez} and Lynn Perkins and Povsic, {Thomas J.} and Etienne Puymirat and Jones, {William Schuyler} and Shah, {Bimal R.} and Sherwood, {Matthew W.} and Kenya Stringfellow and Darin Sujjavanich and Mustafa Toma and Charlene Trotter and {van Diepen}, {Sean F.P.} and Wilson, {Matthew D.} and {Tze-Kay Yan}, Andrew and Schiavi, {Lilia B.} and Marcelo Garrido and Alvarisqueta, {Andr{\'e}s F.} and Sassone, {Sonia A.} and Bordonava, {Anselmo P.} and {Alves De Lima}, {Alberto E.} and Schmidberg, {Jorge M.} and Duronto, {Ernesto A.} and Caruso, {Orlando C.} and Novaretto, {Leonardo P.} and Hominal, {Miguel Angel} and Monta{\~n}a, {Oscar R.} and Alberto Caccavo and {Gomez Vilamajo}, {Oscar A.} and Lorenzatti, {Alberto J.} and Cartasegna, {Luis R.} and Paterlini, {Gustavo A.} and Mackinnon, {Ignacio J.} and Caime, {Guillermo D.} and Marcos Amuchastegui and Oscar Salomone and Codutti, {Oscar R.} and Jure, {Horacio O.} and Bono, {Julio O.E.} and Hrabar, {Adrian D.} and Vallejos, {Julio A.} and {Ahuad Guerrero}, {Rodolfo A.} and Federico Novoa and Patocchi, {Cristian A.} and Zaidman, {Cesar J.} and Giuliano, {Maria E.} and Dran, {Ricardo D.} and Vico, {Marisa L.} and Carnero, {Gabriela S.} and Guzman, {Pablo N.} and {Medrano Allende}, {Juan C.} and {Garcia Brasca}, {Daniela F.} and {Bustamante Labarta}, {Miguel H.} and Sebastian Nani and Blumberg, {Eduardo D.S.} and Colombo, {Hugo R.} and Alberto Liberman and Victorino Fuentealba and Luciardi, {Hector L.} and Waisman, {Gabriel D.} and Berli, {Mario A.} and {Garcia Duran}, {Ruben O.} and Cestari, {Horacio G.} and Luquez, {Hugo A.} and Giordano, {Jorge A.} and Saavedra, {Silvia S.} and Gerardo Zapata and Osvaldo Costamagna and Susana Llois and Waites, {Jonathon H.} and Nicholas Collins and Allan Soward and Hii, {Chris L.S.} and James Shaw and Arstall, {Margaret A.} and John Horowitz and Daniel Ninio and Rogers, {James F.} and David Colquhoun and {Oqueli Flores}, {Romulo E.} and Philip Roberts-Thomson and Owen Raffel and Lehman, {Sam J.} and Constantine Aroney and Coverdale, {Steven G.M.} and Garrahy, {Paul J.} and Gregory Starmer and Mark Sader and Carroll, {Patrick A.} and Ronald Dick and Robert Zweiker and Uta Hoppe and Kurt Huber and Rudolf Berger and Georg Delle-Karth and Bernhard Frey and Dirk Faes and Kurt Hermans and Bruno Pirenne and Attilio Leone and Etienne Hoffer and Vrolix, {Mathias C.M.} and {De Wolf}, Luc and Bart Wollaert and Marc Castadot and Karl Dujardin and Christophe Beauloye and Geert Vervoort and Harry Striekwold and Carl Convens and John Roosen and Emanuele Barbato and Marc Claeys and Frank Cools and Ibrahim Terzic and Fahir Barakovic and Zlatko Midzic and Belma Pojskic and Emir Fazlibegovic and Azra Durak-Nalbantic and Mehmed Kuli{\'c} and Simon Robinson and Richard Davies and Jingfeng Wang and Yi Feng and David Alan and Nielsen, {Peter Kaiser} and Simon Smith and David Henderson",

year = "2021",

month = aug,

day = "3",

doi = "10.1016/j.jacc.2021.04.102",

language = "English",

volume = "78",

pages = "421--433",

journal = "Journal of The American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier",

number = "5",

}

Schwartz, GG, Szarek, M, Bittner, VA, Diaz, R, Goodman, SG, Jukema, JW, Landmesser, U, López-Jaramillo, P, Manvelian, G, Pordy, R, Scemama, M, Sinnaeve, P, White, HD, Gabriel Steg, P, ODYSSEY OUTCOMES Committees and Investigators, Aylward, PE & Lehman, SJ 2021, 'Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol', Journal of The American College of Cardiology, vol. 78, no. 5, pp. 421-433. https://doi.org/10.1016/j.jacc.2021.04.102

TY - JOUR

T1 - Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol

AU - Schwartz, Gregory G.

AU - Szarek, Michael

AU - Bittner, Vera A.

AU - Diaz, Rafael

AU - Goodman, Shaun G.

AU - Jukema, J. Wouter

AU - Landmesser, Ulf

AU - López-Jaramillo, Patricio

AU - Manvelian, Garen

AU - Pordy, Robert

AU - Scemama, Michel

AU - Sinnaeve, Peter

AU - White, Harvey D.

AU - Gabriel Steg, Ph

AU - ODYSSEY OUTCOMES Committees and Investigators

AU - Bhatt, Deepak L.

AU - Harrington, Robert A.

AU - Zeiher, Andreas M.

AU - Tricoci, Pierluigi

AU - Roe, Matthew T.

AU - Mahaffey, Kenneth W.

AU - Edelberg, Jay M.

AU - Hanotin, Corinne

AU - Lecorps, Guillaume

AU - Moryusef, Angèle

AU - Sasiela, William J.

AU - Tamby, Jean François

AU - Aylward, Philip E.

AU - Drexel, Heinz

AU - Dilic, Mirza

AU - Lopes, Renato D.

AU - Gotcheva, Nina N.

AU - Prieto, Juan Carlos

AU - Yong, Huo

AU - Pećin, Ivan

AU - Reiner, Zeljko

AU - Ostadal, Petr

AU - Poulsen, Steen Hvitfeldt

AU - Viigimaa, Margus

AU - Nieminen, Markku S.

AU - Danchin, Nicolas

AU - Chumburidze, Vakhtang

AU - Marx, Nikolaus

AU - Liberopoulos, Evangelos

AU - Montenegro Valdovinos, Pablo Carlos

AU - Tse, Hung Fat

AU - Kiss, Robert Gabor

AU - Xavier, Denis

AU - Zahger, Doron

AU - Valgimigli, Marco

AU - Kimura, Takeshi

AU - Kim, Hyo Soo

AU - Kim, Sang Hyun

AU - Erglis, Andrejs

AU - Laucevicius, Aleksandras

AU - Kedev, Sasko

AU - Yusoff, Khalid

AU - Ramos López, Gabriel Arturo

AU - Alings, Marco

AU - Halvorsen, Sigrun

AU - Correa Flores, Roger M.

AU - Sy, Rody G.

AU - Budaj, Andrzej

AU - Morais, Joao

AU - Dorobantu, Maria

AU - Karpov, Yuri

AU - Ristic, Arsen D.

AU - Chua, Terrance

AU - Murin, Jan

AU - Fras, Zlatko

AU - Dalby, Anthony J.

AU - Tuñón, José

AU - Asita de Silva, H.

AU - Hagström, Emil

AU - Müller, Christian

AU - Chiang, Chern En

AU - Sritara, Piyamitr

AU - Guneri, Sema

AU - Parkhomenko, Alexander

AU - Ray, Kausik K.

AU - Moriarty, Patrick M.

AU - Vogel, Robert

AU - Chaitman, Bernard

AU - Kelsey, Sheryl F.

AU - Olsson, Anders G.

AU - Rouleau, Jean Lucien

AU - Simoons, Maarten L.

AU - Alexander, Karen

AU - Meloni, Chiara

AU - Rosenson, Robert

AU - Sijbrands, Eric J.G.

AU - Alexander, John H.

AU - Armaganijan, Luciana

AU - Bagai, Akshay

AU - Bahit, Maria Cecilia

AU - Brennan, J. Matthew

AU - Clifton, Shaun

AU - DeVore, Adam D.

AU - Deloatch, Shalonda

AU - Dickey, Sheila

AU - Dombrowski, Keith

AU - Ducrocq, Grégory

AU - Eapen, Zubin

AU - Endsley, Patricia

AU - Eppinger, Arleen

AU - Harrison, Robert W.

AU - Hess, Connie Ng

AU - Hlatky, Mark A.

AU - Jordan, Joseph Dedrick

AU - Knowles, Joshua W.

AU - Kolls, Bradley J.

AU - Kong, David F.

AU - Leonardi, Sergio

AU - Lillis, Linda

AU - Maron, David J.

AU - Marcus, Jill

AU - Mathews, Robin

AU - Mehta, Rajendra H.

AU - Mentz, Robert J.

AU - Moreira, Humberto Graner

AU - Patel, Chetan B.

AU - Pereira, Sabrina Bernardez

AU - Perkins, Lynn

AU - Povsic, Thomas J.

AU - Puymirat, Etienne

AU - Jones, William Schuyler

AU - Shah, Bimal R.

AU - Sherwood, Matthew W.

AU - Stringfellow, Kenya

AU - Sujjavanich, Darin

AU - Toma, Mustafa

AU - Trotter, Charlene

AU - van Diepen, Sean F.P.

AU - Wilson, Matthew D.

AU - Tze-Kay Yan, Andrew

AU - Schiavi, Lilia B.

AU - Garrido, Marcelo

AU - Alvarisqueta, Andrés F.

AU - Sassone, Sonia A.

AU - Bordonava, Anselmo P.

AU - Alves De Lima, Alberto E.

AU - Schmidberg, Jorge M.

AU - Duronto, Ernesto A.

AU - Caruso, Orlando C.

AU - Novaretto, Leonardo P.

AU - Hominal, Miguel Angel

AU - Montaña, Oscar R.

AU - Caccavo, Alberto

AU - Gomez Vilamajo, Oscar A.

AU - Lorenzatti, Alberto J.

AU - Cartasegna, Luis R.

AU - Paterlini, Gustavo A.

AU - Mackinnon, Ignacio J.

AU - Caime, Guillermo D.

AU - Amuchastegui, Marcos

AU - Salomone, Oscar

AU - Codutti, Oscar R.

AU - Jure, Horacio O.

AU - Bono, Julio O.E.

AU - Hrabar, Adrian D.

AU - Vallejos, Julio A.

AU - Ahuad Guerrero, Rodolfo A.

AU - Novoa, Federico

AU - Patocchi, Cristian A.

AU - Zaidman, Cesar J.

AU - Giuliano, Maria E.

AU - Dran, Ricardo D.

AU - Vico, Marisa L.

AU - Carnero, Gabriela S.

AU - Guzman, Pablo N.

AU - Medrano Allende, Juan C.

AU - Garcia Brasca, Daniela F.

AU - Bustamante Labarta, Miguel H.

AU - Nani, Sebastian

AU - Blumberg, Eduardo D.S.

AU - Colombo, Hugo R.

AU - Liberman, Alberto

AU - Fuentealba, Victorino

AU - Luciardi, Hector L.

AU - Waisman, Gabriel D.

AU - Berli, Mario A.

AU - Garcia Duran, Ruben O.

AU - Cestari, Horacio G.

AU - Luquez, Hugo A.

AU - Giordano, Jorge A.

AU - Saavedra, Silvia S.

AU - Zapata, Gerardo

AU - Costamagna, Osvaldo

AU - Llois, Susana

AU - Waites, Jonathon H.

AU - Collins, Nicholas

AU - Soward, Allan

AU - Hii, Chris L.S.

AU - Shaw, James

AU - Arstall, Margaret A.

AU - Horowitz, John

AU - Ninio, Daniel

AU - Rogers, James F.

AU - Colquhoun, David

AU - Oqueli Flores, Romulo E.

AU - Roberts-Thomson, Philip

AU - Raffel, Owen

AU - Lehman, Sam J.

AU - Aroney, Constantine

AU - Coverdale, Steven G.M.

AU - Garrahy, Paul J.

AU - Starmer, Gregory

AU - Sader, Mark

AU - Carroll, Patrick A.

AU - Dick, Ronald

AU - Zweiker, Robert

AU - Hoppe, Uta

AU - Huber, Kurt

AU - Berger, Rudolf

AU - Delle-Karth, Georg

AU - Frey, Bernhard

AU - Faes, Dirk

AU - Hermans, Kurt

AU - Pirenne, Bruno

AU - Leone, Attilio

AU - Hoffer, Etienne

AU - Vrolix, Mathias C.M.

AU - De Wolf, Luc

AU - Wollaert, Bart

AU - Castadot, Marc

AU - Dujardin, Karl

AU - Beauloye, Christophe

AU - Vervoort, Geert

AU - Striekwold, Harry

AU - Convens, Carl

AU - Roosen, John

AU - Barbato, Emanuele

AU - Claeys, Marc

AU - Cools, Frank

AU - Terzic, Ibrahim

AU - Barakovic, Fahir

AU - Midzic, Zlatko

AU - Pojskic, Belma

AU - Fazlibegovic, Emir

AU - Durak-Nalbantic, Azra

AU - Kulić, Mehmed

AU - Robinson, Simon

AU - Davies, Richard

AU - Wang, Jingfeng

AU - Feng, Yi

AU - Alan, David

AU - Nielsen, Peter Kaiser

AU - Smith, Simon

AU - Henderson, David

PY - 2021/8/3

Y1 - 2021/8/3

N2 - Background: Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. Objectives: In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. Methods: ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL (median 69.4 mg/dL; interquartile range: 64.3-74.0 mg/dL); in 14,573 patients (77.0%), both determinations were ≥70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2-111.0 mg/dL). Results: In the lower LDL-C subgroup, MACE rates were 4.2 and 3.1 per 100 patient-years among placebo-treated patients with baseline lipoprotein(a) greater than or less than or equal to the median (13.7 mg/dL). Corresponding adjusted treatment hazard ratios were 0.68 (95% confidence interval [CI]: 0.52-0.90) and 1.11 (95% CI: 0.83-1.49), with treatment-lipoprotein(a) interaction on MACE (Pinteraction = 0.017). In the higher LDL-C subgroup, MACE rates were 4.7 and 3.8 per 100 patient-years among placebo-treated patients with lipoprotein(a) >13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with Pinteraction = 0.43. Conclusions: In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402)

AB - Background: Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. Objectives: In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. Methods: ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL (median 69.4 mg/dL; interquartile range: 64.3-74.0 mg/dL); in 14,573 patients (77.0%), both determinations were ≥70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2-111.0 mg/dL). Results: In the lower LDL-C subgroup, MACE rates were 4.2 and 3.1 per 100 patient-years among placebo-treated patients with baseline lipoprotein(a) greater than or less than or equal to the median (13.7 mg/dL). Corresponding adjusted treatment hazard ratios were 0.68 (95% confidence interval [CI]: 0.52-0.90) and 1.11 (95% CI: 0.83-1.49), with treatment-lipoprotein(a) interaction on MACE (Pinteraction = 0.017). In the higher LDL-C subgroup, MACE rates were 4.7 and 3.8 per 100 patient-years among placebo-treated patients with lipoprotein(a) >13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with Pinteraction = 0.43. Conclusions: In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402)

KW - acute coronary syndrome

KW - lipoprotein(a)

KW - low-density lipoprotein cholesterol

KW - PCSK9 inhibitor

UR - http://www.scopus.com/inward/record.url?scp=85110291084&partnerID=8YFLogxK

U2 - 10.1016/j.jacc.2021.04.102

DO - 10.1016/j.jacc.2021.04.102

M3 - Article

AN - SCOPUS:85110291084

SN - 0735-1097

VL - 78

SP - 421

EP - 433

JO - Journal of The American College of Cardiology

JF - Journal of The American College of Cardiology

IS - 5

ER -

Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol

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