Relation of Lipoprotein(a) Levels to Incident Type 2 Diabetes and Modification by Alirocumab Treatment

Gregory G. Schwartz; Michael Szarek; Vera A. Bittner; Deepak L. Bhatt; Rafael Diaz; Shaun G. Goodman; J. Wouter Jukema; Megan Loy; Garen Manvelian; Robert Pordy; Harvey D. White; Philippe Gabriel Steg; ODYSSEY OUTCOMES Committees and Investigators; Shaun Goodman; Robert Harrington; Andreas M. Zeiher; Pierluigi Tricoci; Matthew Roe; Kenneth W. Mahaffey; Jay M. Edelberg; Corinne Hanotin; Guillaume Lecorps; Angèle Moryusef; William J. Sasiela; Jean François Tamby; Philip Aylward; H. Drexel; Peter Sinnaeve; Mirza Dilic; Renato D. Lopes; Nina N. Gotcheva; Juan Carlos Prieto; Huo Yong; Patricio Lopez-Jaramillo; Ivan Pećin; Zeljko Reiner; Petr Ostadal; Steen Hvitfeldt Poulsen; Margus Viigimaa; Markku S. Nieminen; Nicolas Danchin; Vakhtang Chumburidze; Nikolaus Marx; Evangelos Liberopoulos; Pablo Carlos Montenegro Valdovinos; Hung-Fat Tse; Robert Gabor Kiss; Denis Xavier; Doron Zahger; Marco Valgimigli; Takeshi Kimura; Hyo-Soo Kim; Sang Hyun Kim; Andrejs Erglis; Aleksandras Laucevicius; Sasko Kedev; Khalid Yusoff; Gabriel Arturo Ramos López; M. Alings; Sigrun Halvorsen; Roger M. Correa Flores; Rody Sy; Andrzej Budaj; Joao Morais; Maria  Dorobantu; Yuri Karpov; Arsen D. Ristic; Terrance Chua; Jan Murin; Zlatko Fras; Anthony Dalby; José Tuñón; H. Asita de Silva; Emil Hagstrom; Ulf Landmesser; Christian Muller; Chern En Chiang; Piyamitr Sritara; Sema Guneri; Alexander Parkhomenko; Kausik K. Ray; Patrick M. Moriarty; Matthew T. Roe; Robert Vogel; Bernard Chaitman; Sheryl F. Kelsey; Anders G. Olsson; Jean-Lucien Rouleau; Maarten Simoons; Karen Alexander; Chiara Meloni; Robert Rosenson; Eric Sijbrands; Pierluigi Tricoci; John H. Alexander; Luciana Armaganijan; Akshay Bagai; Maria Bahit; J. Matthew Brennan; Shaun Clifton; Adam D. DeVore; Shalonda Deloatch; Sheila Dickey; Keith Dombrowski; Grégory Ducrocq; Zubin Eapen; Patricia Endsley; Arleen Eppinger; Robert W. Harrison; Connie Ng Hess; Mark A. Hlatky; Joseph Dedrick Jordan; Joshua W. Knowles; Bradley J. Kolls; Kong David F; Sergio Leonardi; Linda Lillis; Renato D. Lopes; David J. Maron; Kenneth W. Mahaffey; Jill Marcus; Robin Mathews; Rajendra H. Mehta; Robert J. Mentz; Humberto Graner Moreira; Chetan B. Patel; Sabrina Bernardez Pereira; Lynn Perkins; Thomas J. Povsic; Etienne Puymirat; Matthew T. Roe; William Schuyler Jones; Bimal R. Shah; Matthew W. Sherwood; Kenya Stringfellow; Darin Sujjavanich; Mustafa Toma; Charlene Trotter; Sean van Diepen; Matthew D. Wilson; Andrew T. Yan; Lilia Schiavi; MARCELO GARRIDO; Andrés F. Alvarisqueta; Sonia A. Sassone; ANSELMO PAULINO BORDONAVA; Alberto E. Alves De Lima; Jorge M. Schmidberg; Ernesto A. Duronto; Orlando C. Caruso; LEONARDO NOVARETTO; Miguel Angel Hominal; Oscar Montana; ALBERTO CACCAVO; Oscar Gomez Vilamajo; Alberto J. Lorenzatti; L.R.  Cartasegna; Gustavo A. Paterlini; Ignacio J Mackinnon; G. D. Caime; Marcos Amuchastegui; Oscar Salomone; Oscar R. Codutti; Horacio O. Jure; Julio OE Bono; Adrian Hrabar; Julio A. Vallejos; Rodolfo Andres Ahuad Guerrero; Federico Novoa; Cristian A. Patocchi; Cesar Zaidman; Maria E. Giuliano; Ricardo Dario Dran; Marisa Vico; Gabriela S. Carnero; Pablo N. Guzman; Juan C. Medrano Allende; Daniela F. Garcia Brasca; Miguel H. Bustamante Labarta; Sebastian Nani; Eduardo DS Blumberg; Hugo R. Colombo; A. G. Liberman; Victorino Fuentealba; Hector Lucas Luciardi; Gabriel D. Waisman; Mario A. Berli; Ruben Omar Garcia Duran; Horacio G. Cestari; Hugo A  Luquez; Jorge A. Giordano; Silvia S. Saavedra; Gerardo Zapata; Osvaldo Costamagna; Susana Llois; Jonathon Waites; Nicholas Collins; Allan Soward; Philip Aylward; Chris LS Hii; James Shaw; Margaret Arstall; John Horowitz; D. Ninio; James F. Rogers; David Colquhoun; Romulo E.Oqueli Flores; Philip Roberts-Thomson; Owen Raffel; Sam Lehman; Constantine Aroney; Steve G Coverdale; Paul J. Garrahy; Gregory Starmer; Mark Sader; Patrick A. Carroll; Ronald Dick; Robert Zweiker; Uta Hoppe; H. Drexel; Kurt Huber; Rudolf Berger; Georg Delle-Karth; Bernhard Frey; Franz Weidinger; Dirk Faes; Kurt Hermans; Bruno Pirenne; Attilio Leone; Etienne Hoffer; Peter Sinnaeve; Mathias CM Vrolix; Luc De Wolf; Bart Wollaert; Marc Castadot; Karl Dujardin; Christophe Beauloye; Geert Vervoort; Harry Striekwold; Carl Convens; John Roosen; Emanuele Barbato; Marc Claeys; Frank Cools; Ibrahim Terzic; Fahir Barakovic; Zlatko Midzic; Belma Pojskic; Emir Fazlibegovic; Mirza Dilic; Azra Durak-Nalbantic; Mehmed Kulic; Dusko Vulic; Adis Muslibegovic; Boris Goronja

doi:10.2337/dc20-2842

Relation of Lipoprotein(a) Levels to Incident Type 2 Diabetes and Modification by Alirocumab Treatment

Gregory G. Schwartz, Michael Szarek, Vera A. Bittner, Deepak L. Bhatt, Rafael Diaz, Shaun G. Goodman, J. Wouter Jukema, Megan Loy, Garen Manvelian, Robert Pordy, Harvey D. White, Philippe Gabriel Steg, ODYSSEY OUTCOMES Committees and Investigators, Shaun Goodman, Robert Harrington, Andreas M. Zeiher, Pierluigi Tricoci, Matthew Roe, Kenneth W. Mahaffey, Jay M. EdelbergCorinne Hanotin, Guillaume Lecorps, Angèle Moryusef, William J. Sasiela, Jean François Tamby, Philip Aylward, H. Drexel, Peter Sinnaeve, Mirza Dilic, Renato D. Lopes, Nina N. Gotcheva, Juan Carlos Prieto, Huo Yong, Patricio Lopez-Jaramillo, Ivan Pećin, Zeljko Reiner, Petr Ostadal, Steen Hvitfeldt Poulsen, Margus Viigimaa, Markku S. Nieminen, Nicolas Danchin, Vakhtang Chumburidze, Nikolaus Marx, Evangelos Liberopoulos, Pablo Carlos Montenegro Valdovinos, Hung-Fat Tse, Robert Gabor Kiss, Denis Xavier, Doron Zahger, Marco Valgimigli, Takeshi Kimura, Hyo-Soo Kim, Sang Hyun Kim, Andrejs Erglis, Aleksandras Laucevicius, Sasko Kedev, Khalid Yusoff, Gabriel Arturo Ramos López, M. Alings, Sigrun Halvorsen, Roger M. Correa Flores, Rody Sy, Andrzej Budaj, Joao Morais, Maria Dorobantu, Yuri Karpov, Arsen D. Ristic, Terrance Chua, Jan Murin, Zlatko Fras, Anthony Dalby, José Tuñón, H. Asita de Silva, Emil Hagstrom, Ulf Landmesser, Christian Muller, Chern En Chiang, Piyamitr Sritara, Sema Guneri, Alexander Parkhomenko, Kausik K. Ray, Patrick M. Moriarty, Matthew T. Roe, Robert Vogel, Bernard Chaitman, Sheryl F. Kelsey, Anders G. Olsson, Jean-Lucien Rouleau, Maarten Simoons, Karen Alexander, Chiara Meloni, Robert Rosenson, Eric Sijbrands, Pierluigi Tricoci, John H. Alexander, Luciana Armaganijan, Akshay Bagai, Maria Bahit, J. Matthew Brennan, Shaun Clifton, Adam D. DeVore, Shalonda Deloatch, Sheila Dickey, Keith Dombrowski, Grégory Ducrocq, Zubin Eapen, Patricia Endsley, Arleen Eppinger, Robert W. Harrison, Connie Ng Hess, Mark A. Hlatky, Joseph Dedrick Jordan, Joshua W. Knowles, Bradley J. Kolls, Kong David F, Sergio Leonardi, Linda Lillis, Renato D. Lopes, David J. Maron, Kenneth W. Mahaffey, Jill Marcus, Robin Mathews, Rajendra H. Mehta, Robert J. Mentz, Humberto Graner Moreira, Chetan B. Patel, Sabrina Bernardez Pereira, Lynn Perkins, Thomas J. Povsic, Etienne Puymirat, Matthew T. Roe, William Schuyler Jones, Bimal R. Shah, Matthew W. Sherwood, Kenya Stringfellow, Darin Sujjavanich, Mustafa Toma, Charlene Trotter, Sean van Diepen, Matthew D. Wilson, Andrew T. Yan, Lilia Schiavi, MARCELO GARRIDO, Andrés F. Alvarisqueta, Sonia A. Sassone, ANSELMO PAULINO BORDONAVA, Alberto E. Alves De Lima, Jorge M. Schmidberg, Ernesto A. Duronto, Orlando C. Caruso, LEONARDO NOVARETTO, Miguel Angel Hominal, Oscar Montana, ALBERTO CACCAVO, Oscar Gomez Vilamajo, Alberto J. Lorenzatti, L.R. Cartasegna, Gustavo A. Paterlini, Ignacio J Mackinnon, G. D. Caime, Marcos Amuchastegui, Oscar Salomone, Oscar R. Codutti, Horacio O. Jure, Julio OE Bono, Adrian Hrabar, Julio A. Vallejos, Rodolfo Andres Ahuad Guerrero, Federico Novoa, Cristian A. Patocchi, Cesar Zaidman, Maria E. Giuliano, Ricardo Dario Dran, Marisa Vico, Gabriela S. Carnero, Pablo N. Guzman, Juan C. Medrano Allende, Daniela F. Garcia Brasca, Miguel H. Bustamante Labarta, Sebastian Nani, Eduardo DS Blumberg, Hugo R. Colombo, A. G. Liberman, Victorino Fuentealba, Hector Lucas Luciardi, Gabriel D. Waisman, Mario A. Berli, Ruben Omar Garcia Duran, Horacio G. Cestari, Hugo A Luquez, Jorge A. Giordano, Silvia S. Saavedra, Gerardo Zapata, Osvaldo Costamagna, Susana Llois, Jonathon Waites, Nicholas Collins, Allan Soward, Philip Aylward, Chris LS Hii, James Shaw, Margaret Arstall, John Horowitz, D. Ninio, James F. Rogers, David Colquhoun, Romulo E.Oqueli Flores, Philip Roberts-Thomson, Owen Raffel, Sam Lehman, Constantine Aroney, Steve G Coverdale, Paul J. Garrahy, Gregory Starmer, Mark Sader, Patrick A. Carroll, Ronald Dick, Robert Zweiker, Uta Hoppe, H. Drexel, Kurt Huber, Rudolf Berger, Georg Delle-Karth, Bernhard Frey, Franz Weidinger, Dirk Faes, Kurt Hermans, Bruno Pirenne, Attilio Leone, Etienne Hoffer, Peter Sinnaeve, Mathias CM Vrolix, Luc De Wolf, Bart Wollaert, Marc Castadot, Karl Dujardin, Christophe Beauloye, Geert Vervoort, Harry Striekwold, Carl Convens, John Roosen, Emanuele Barbato, Marc Claeys, Frank Cools, Ibrahim Terzic, Fahir Barakovic, Zlatko Midzic, Belma Pojskic, Emir Fazlibegovic, Mirza Dilic, Azra Durak-Nalbantic, Mehmed Kulic, Dusko Vulic, Adis Muslibegovic, Boris Goronja

College of Medicine and Public Health

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

22 Citations (Scopus)

Abstract

OBJECTIVE: In observational data, lower levels of lipoprotein(a) have been associated with greater prevalence of type 2 diabetes. Whether pharmacologic lowering of lipoprotein(a) influences incident type 2 diabetes is unknown. We determined the relationship of lipoprotein(a) concentration with incident type 2 diabetes and effects of treatment with alirocumab, a PCSK9 inhibitor. RESEARCH DESIGN AND METHODS: In the ODYSSEY OUTCOMES trial alirocumab was compared with placebo in patients with acute coronary syndrome. Incident diabetes was determined from laboratory, medication, and adverse event data. RESULTS: Among 13,480 patients without diabetes at baseline, 1,324 developed type 2 diabetes over a median 2.7 years. Median baseline lipoprotein(a) was 21.9 mg/dL. With placebo, 10 mg/dL lower baseline lipoprotein(a) was associated with hazard ratio 1.04 (95% CI 1.02-1.06, P < 0.001) for incident type 2 diabetes. Alirocumab reduced lipoprotein(a) by a median 23.2% with greater absolute reductions from higher baseline levels and no overall effect on incident type 2 diabetes (hazard ratio 0.95, 95% CI 0.85-1.05). At low baseline lipoprotein(a) levels, alirocumab tended to reduce incident type 2 diabetes, while at high baseline lipoprotein(a) alirocumab tended to increase incident type 2 diabetes compared with placebo (treatment-baseline lipoprotein(a) interaction P = 0.006). In the alirocumab group, a 10 mg/dL decrease in lipoprotein(a) from baseline was associated with hazard ratio 1.07 (95% CI 1.03-1.12; P = 0.0002) for incident type 2 diabetes. CONCLUSIONS: In patients with acute coronary syndrome, baseline lipoprotein(a) concentration associated inversely with incident type 2 diabetes. Alirocumab had neutral overall effect on incident type 2 diabetes. However, treatment-related reductions in lipoprotein(a), more pronounced from high baseline levels, were associated with increased risk of incident type 2 diabetes. Whether these findings pertain to other therapies that reduce lipoprotein(a) is undetermined.

Original language	English
Pages (from-to)	1219-1227
Number of pages	9
Journal	Diabetes Care
Volume	44
Issue number	5
Early online date	15 Mar 2021
DOIs	https://doi.org/10.2337/dc20-2842
Publication status	Published - May 2021

Keywords

lipoprotein(a)
Type 2 Diabetes
Alirocumab
PCSK9 inhibitors

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.2337/dc20-2842Licence: In Copyright

Cite this

Schwartz, G. G., Szarek, M., Bittner, V. A., Bhatt, D. L., Diaz, R., Goodman, S. G., Jukema, J. W., Loy, M., Manvelian, G., Pordy, R., White, H. D., Steg, P. G., ODYSSEY OUTCOMES Committees and Investigators, Goodman, S., Harrington, R., Zeiher, A. M., Tricoci, P., Roe, M., Mahaffey, K. W., ... Goronja, B. (2021). Relation of Lipoprotein(a) Levels to Incident Type 2 Diabetes and Modification by Alirocumab Treatment. Diabetes Care, 44(5), 1219-1227. https://doi.org/10.2337/dc20-2842

@article{9cf0b6f2818540378c75335de7736cd4,

title = "Relation of Lipoprotein(a) Levels to Incident Type 2 Diabetes and Modification by Alirocumab Treatment",

abstract = "OBJECTIVE: In observational data, lower levels of lipoprotein(a) have been associated with greater prevalence of type 2 diabetes. Whether pharmacologic lowering of lipoprotein(a) influences incident type 2 diabetes is unknown. We determined the relationship of lipoprotein(a) concentration with incident type 2 diabetes and effects of treatment with alirocumab, a PCSK9 inhibitor. RESEARCH DESIGN AND METHODS: In the ODYSSEY OUTCOMES trial alirocumab was compared with placebo in patients with acute coronary syndrome. Incident diabetes was determined from laboratory, medication, and adverse event data. RESULTS: Among 13,480 patients without diabetes at baseline, 1,324 developed type 2 diabetes over a median 2.7 years. Median baseline lipoprotein(a) was 21.9 mg/dL. With placebo, 10 mg/dL lower baseline lipoprotein(a) was associated with hazard ratio 1.04 (95% CI 1.02-1.06, P < 0.001) for incident type 2 diabetes. Alirocumab reduced lipoprotein(a) by a median 23.2% with greater absolute reductions from higher baseline levels and no overall effect on incident type 2 diabetes (hazard ratio 0.95, 95% CI 0.85-1.05). At low baseline lipoprotein(a) levels, alirocumab tended to reduce incident type 2 diabetes, while at high baseline lipoprotein(a) alirocumab tended to increase incident type 2 diabetes compared with placebo (treatment-baseline lipoprotein(a) interaction P = 0.006). In the alirocumab group, a 10 mg/dL decrease in lipoprotein(a) from baseline was associated with hazard ratio 1.07 (95% CI 1.03-1.12; P = 0.0002) for incident type 2 diabetes. CONCLUSIONS: In patients with acute coronary syndrome, baseline lipoprotein(a) concentration associated inversely with incident type 2 diabetes. Alirocumab had neutral overall effect on incident type 2 diabetes. However, treatment-related reductions in lipoprotein(a), more pronounced from high baseline levels, were associated with increased risk of incident type 2 diabetes. Whether these findings pertain to other therapies that reduce lipoprotein(a) is undetermined.",

keywords = "lipoprotein(a), Type 2 Diabetes, Alirocumab, PCSK9 inhibitors",

author = "Schwartz, {Gregory G.} and Michael Szarek and Bittner, {Vera A.} and Bhatt, {Deepak L.} and Rafael Diaz and Goodman, {Shaun G.} and Jukema, {J. Wouter} and Megan Loy and Garen Manvelian and Robert Pordy and White, {Harvey D.} and Steg, {Philippe Gabriel} and {ODYSSEY OUTCOMES Committees and Investigators} and Shaun Goodman and Robert Harrington and Zeiher, {Andreas M.} and Pierluigi Tricoci and Matthew Roe 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 Philip Aylward and H. Drexel and Peter Sinnaeve and Mirza Dilic and Lopes, {Renato D.} and Gotcheva, {Nina N.} and Prieto, {Juan Carlos} and Huo Yong and Patricio Lopez-Jaramillo 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 Valdovinos, {Pablo Carlos Montenegro} and Hung-Fat Tse and Kiss, {Robert Gabor} and Denis Xavier and Doron Zahger and Marco Valgimigli and Takeshi Kimura and Hyo-Soo Kim and Kim, {Sang Hyun} and Andrejs Erglis and Aleksandras Laucevicius and Sasko Kedev and Khalid Yusoff and {Ramos L{\'o}pez}, {Gabriel Arturo} and M. Alings and Sigrun Halvorsen and {Correa Flores}, {Roger M.} and Rody Sy 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 Anthony Dalby and Jos{\'e} Tu{\~n}{\'o}n and {de Silva}, {H. Asita} and Emil Hagstrom and Ulf Landmesser and Christian Muller and Chiang, {Chern En} and Piyamitr Sritara and Sema Guneri and Alexander Parkhomenko and Ray, {Kausik K.} and Moriarty, {Patrick M.} and Roe, {Matthew T.} and Robert Vogel and Bernard Chaitman and Kelsey, {Sheryl F.} and Olsson, {Anders G.} and Jean-Lucien Rouleau and Maarten Simoons and Karen Alexander and Chiara Meloni and Robert Rosenson and Eric Sijbrands and Pierluigi Tricoci and Alexander, {John H.} and Luciana Armaganijan and Akshay Bagai and Maria Bahit 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 {David F}, Kong and Sergio Leonardi and Linda Lillis and Lopes, {Renato D.} and Maron, {David J.} and Mahaffey, {Kenneth W.} 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 Roe, {Matthew T.} 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 and Wilson, {Matthew D.} and Yan, {Andrew T.} and Lilia Schiavi and MARCELO GARRIDO and Alvarisqueta, {Andr{\'e}s F.} and Sassone, {Sonia A.} and BORDONAVA, {ANSELMO PAULINO} and {Alves De Lima}, {Alberto E.} and Schmidberg, {Jorge M.} and Duronto, {Ernesto A.} and Caruso, {Orlando C.} and LEONARDO NOVARETTO and {Angel Hominal}, Miguel and Oscar Montana and ALBERTO CACCAVO and {Gomez Vilamajo}, Oscar and Lorenzatti, {Alberto J.} and L.R. Cartasegna and Paterlini, {Gustavo A.} and Mackinnon, {Ignacio J} and Caime, {G. D.} and Marcos Amuchastegui and Oscar Salomone and Codutti, {Oscar R.} and Jure, {Horacio O.} and Bono, {Julio OE} and Adrian Hrabar and Vallejos, {Julio A.} and {Ahuad Guerrero}, {Rodolfo Andres} and Federico Novoa and Patocchi, {Cristian A.} and Cesar Zaidman and Giuliano, {Maria E.} and Dran, {Ricardo Dario} and Marisa Vico 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 DS} and Colombo, {Hugo R.} and Liberman, {A. G.} and Victorino Fuentealba and Luciardi, {Hector Lucas} and Waisman, {Gabriel D.} and Berli, {Mario A.} and {Garcia Duran}, {Ruben Omar} 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 Jonathon Waites and Nicholas Collins and Allan Soward and Philip Aylward and Hii, {Chris LS} and James Shaw and Margaret Arstall and John Horowitz and D. Ninio and Rogers, {James F.} and David Colquhoun and Flores, {Romulo E.Oqueli} and Philip Roberts-Thomson and Owen Raffel and Sam Lehman and Constantine Aroney and Coverdale, {Steve G} and Garrahy, {Paul J.} and Gregory Starmer and Mark Sader and Carroll, {Patrick A.} and Ronald Dick and Robert Zweiker and Uta Hoppe and H. Drexel and Kurt Huber and Rudolf Berger and Georg Delle-Karth and Bernhard Frey and Franz Weidinger and Dirk Faes and Kurt Hermans and Bruno Pirenne and Attilio Leone and Etienne Hoffer and Peter Sinnaeve and Vrolix, {Mathias CM} 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 Mirza Dilic and Azra Durak-Nalbantic and Mehmed Kulic and Dusko Vulic and Adis Muslibegovic and Boris Goronja",

year = "2021",

month = may,

doi = "10.2337/dc20-2842",

language = "English",

volume = "44",

pages = "1219--1227",

journal = "Diabetes Care",

issn = "0149-5992",

publisher = "AMERICAN DIABETES ASSOCIATION",

number = "5",

}

Schwartz, GG, Szarek, M, Bittner, VA, Bhatt, DL, Diaz, R, Goodman, SG, Jukema, JW, Loy, M, Manvelian, G, Pordy, R, White, HD, Steg, PG, ODYSSEY OUTCOMES Committees and Investigators, Goodman, S, Harrington, R, Zeiher, AM, Tricoci, P, Roe, M, Mahaffey, KW, Edelberg, JM, Hanotin, C, Lecorps, G, Moryusef, A, Sasiela, WJ, Tamby, JF, Aylward, P, Drexel, H, Sinnaeve, P, Dilic, M, Lopes, RD, Gotcheva, NN, Prieto, JC, Yong, H, Lopez-Jaramillo, P, Pećin, I, Reiner, Z, Ostadal, P, Poulsen, SH, Viigimaa, M, Nieminen, MS, Danchin, N, Chumburidze, V, Marx, N, Liberopoulos, E, Valdovinos, PCM, Tse, H-F, Kiss, RG, Xavier, D, Zahger, D, Valgimigli, M, Kimura, T, Kim, H-S, Kim, SH, Erglis, A, Laucevicius, A, Kedev, S, Yusoff, K, Ramos López, GA, Alings, M, Halvorsen, S, Correa Flores, RM, Sy, R, Budaj, A, Morais, J, Dorobantu, M, Karpov, Y, Ristic, AD, Chua, T, Murin, J, Fras, Z, Dalby, A, Tuñón, J, de Silva, HA, Hagstrom, E, Landmesser, U, Muller, C, Chiang, CE, Sritara, P, Guneri, S, Parkhomenko, A, Ray, KK, Moriarty, PM, Roe, MT, Vogel, R, Chaitman, B, Kelsey, SF, Olsson, AG, Rouleau, J-L, Simoons, M, Alexander, K, Meloni, C, Rosenson, R, Sijbrands, E, Tricoci, P, Alexander, JH, Armaganijan, L, Bagai, A, Bahit, M, Brennan, JM, Clifton, S, DeVore, AD, Deloatch, S, Dickey, S, Dombrowski, K, Ducrocq, G, Eapen, Z, Endsley, P, Eppinger, A, Harrison, RW, Hess, CN, Hlatky, MA, Jordan, JD, Knowles, JW, Kolls, BJ, David F, K, Leonardi, S, Lillis, L, Lopes, RD, Maron, DJ, Mahaffey, KW, Marcus, J, Mathews, R, Mehta, RH, Mentz, RJ, Moreira, HG, Patel, CB, Pereira, SB, Perkins, L, Povsic, TJ, Puymirat, E, Roe, MT, Jones, WS, Shah, BR, Sherwood, MW, Stringfellow, K, Sujjavanich, D, Toma, M, Trotter, C, van Diepen, S, Wilson, MD, Yan, AT, Schiavi, L, GARRIDO, MARCELO, Alvarisqueta, AF, Sassone, SA, BORDONAVA, ANSELMOPAULINO, Alves De Lima, AE, Schmidberg, JM, Duronto, EA, Caruso, OC, NOVARETTO, LEONARDO, Angel Hominal, M, Montana, O, CACCAVO, ALBERTO, Gomez Vilamajo, O, Lorenzatti, AJ, Cartasegna, LR, Paterlini, GA, Mackinnon, IJ, Caime, GD, Amuchastegui, M, Salomone, O, Codutti, OR, Jure, HO, Bono, JOE, Hrabar, A, Vallejos, JA, Ahuad Guerrero, RA, Novoa, F, Patocchi, CA, Zaidman, C, Giuliano, ME, Dran, RD, Vico, M, Carnero, GS, Guzman, PN, Medrano Allende, JC, Garcia Brasca, DF, Bustamante Labarta, MH, Nani, S, Blumberg, EDS, Colombo, HR, Liberman, AG, Fuentealba, V, Luciardi, HL, Waisman, GD, Berli, MA, Garcia Duran, RO, Cestari, HG, Luquez, HA, Giordano, JA, Saavedra, SS, Zapata, G, Costamagna, O, Llois, S, Waites, J, Collins, N, Soward, A, Aylward, P, Hii, CLS, Shaw, J, Arstall, M, Horowitz, J, Ninio, D, Rogers, JF, Colquhoun, D, Flores, REO, Roberts-Thomson, P, Raffel, O, Lehman, S, Aroney, C, Coverdale, SG, Garrahy, PJ, Starmer, G, Sader, M, Carroll, PA, Dick, R, Zweiker, R, Hoppe, U, Drexel, H, Huber, K, Berger, R, Delle-Karth, G, Frey, B, Weidinger, F, Faes, D, Hermans, K, Pirenne, B, Leone, A, Hoffer, E, Sinnaeve, P, Vrolix, MCM, De Wolf, L, Wollaert, B, Castadot, M, Dujardin, K, Beauloye, C, Vervoort, G, Striekwold, H, Convens, C, Roosen, J, Barbato, E, Claeys, M, Cools, F, Terzic, I, Barakovic, F, Midzic, Z, Pojskic, B, Fazlibegovic, E, Dilic, M, Durak-Nalbantic, A, Kulic, M, Vulic, D, Muslibegovic, A & Goronja, B 2021, 'Relation of Lipoprotein(a) Levels to Incident Type 2 Diabetes and Modification by Alirocumab Treatment', Diabetes Care, vol. 44, no. 5, pp. 1219-1227. https://doi.org/10.2337/dc20-2842

TY - JOUR

T1 - Relation of Lipoprotein(a) Levels to Incident Type 2 Diabetes and Modification by Alirocumab Treatment

AU - Schwartz, Gregory G.

AU - Szarek, Michael

AU - Bittner, Vera A.

AU - Bhatt, Deepak L.

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AU - Dujardin, Karl

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PY - 2021/5

Y1 - 2021/5

N2 - OBJECTIVE: In observational data, lower levels of lipoprotein(a) have been associated with greater prevalence of type 2 diabetes. Whether pharmacologic lowering of lipoprotein(a) influences incident type 2 diabetes is unknown. We determined the relationship of lipoprotein(a) concentration with incident type 2 diabetes and effects of treatment with alirocumab, a PCSK9 inhibitor. RESEARCH DESIGN AND METHODS: In the ODYSSEY OUTCOMES trial alirocumab was compared with placebo in patients with acute coronary syndrome. Incident diabetes was determined from laboratory, medication, and adverse event data. RESULTS: Among 13,480 patients without diabetes at baseline, 1,324 developed type 2 diabetes over a median 2.7 years. Median baseline lipoprotein(a) was 21.9 mg/dL. With placebo, 10 mg/dL lower baseline lipoprotein(a) was associated with hazard ratio 1.04 (95% CI 1.02-1.06, P < 0.001) for incident type 2 diabetes. Alirocumab reduced lipoprotein(a) by a median 23.2% with greater absolute reductions from higher baseline levels and no overall effect on incident type 2 diabetes (hazard ratio 0.95, 95% CI 0.85-1.05). At low baseline lipoprotein(a) levels, alirocumab tended to reduce incident type 2 diabetes, while at high baseline lipoprotein(a) alirocumab tended to increase incident type 2 diabetes compared with placebo (treatment-baseline lipoprotein(a) interaction P = 0.006). In the alirocumab group, a 10 mg/dL decrease in lipoprotein(a) from baseline was associated with hazard ratio 1.07 (95% CI 1.03-1.12; P = 0.0002) for incident type 2 diabetes. CONCLUSIONS: In patients with acute coronary syndrome, baseline lipoprotein(a) concentration associated inversely with incident type 2 diabetes. Alirocumab had neutral overall effect on incident type 2 diabetes. However, treatment-related reductions in lipoprotein(a), more pronounced from high baseline levels, were associated with increased risk of incident type 2 diabetes. Whether these findings pertain to other therapies that reduce lipoprotein(a) is undetermined.

AB - OBJECTIVE: In observational data, lower levels of lipoprotein(a) have been associated with greater prevalence of type 2 diabetes. Whether pharmacologic lowering of lipoprotein(a) influences incident type 2 diabetes is unknown. We determined the relationship of lipoprotein(a) concentration with incident type 2 diabetes and effects of treatment with alirocumab, a PCSK9 inhibitor. RESEARCH DESIGN AND METHODS: In the ODYSSEY OUTCOMES trial alirocumab was compared with placebo in patients with acute coronary syndrome. Incident diabetes was determined from laboratory, medication, and adverse event data. RESULTS: Among 13,480 patients without diabetes at baseline, 1,324 developed type 2 diabetes over a median 2.7 years. Median baseline lipoprotein(a) was 21.9 mg/dL. With placebo, 10 mg/dL lower baseline lipoprotein(a) was associated with hazard ratio 1.04 (95% CI 1.02-1.06, P < 0.001) for incident type 2 diabetes. Alirocumab reduced lipoprotein(a) by a median 23.2% with greater absolute reductions from higher baseline levels and no overall effect on incident type 2 diabetes (hazard ratio 0.95, 95% CI 0.85-1.05). At low baseline lipoprotein(a) levels, alirocumab tended to reduce incident type 2 diabetes, while at high baseline lipoprotein(a) alirocumab tended to increase incident type 2 diabetes compared with placebo (treatment-baseline lipoprotein(a) interaction P = 0.006). In the alirocumab group, a 10 mg/dL decrease in lipoprotein(a) from baseline was associated with hazard ratio 1.07 (95% CI 1.03-1.12; P = 0.0002) for incident type 2 diabetes. CONCLUSIONS: In patients with acute coronary syndrome, baseline lipoprotein(a) concentration associated inversely with incident type 2 diabetes. Alirocumab had neutral overall effect on incident type 2 diabetes. However, treatment-related reductions in lipoprotein(a), more pronounced from high baseline levels, were associated with increased risk of incident type 2 diabetes. Whether these findings pertain to other therapies that reduce lipoprotein(a) is undetermined.

KW - lipoprotein(a)

KW - Type 2 Diabetes

KW - Alirocumab

KW - PCSK9 inhibitors

UR - http://www.scopus.com/inward/record.url?scp=85106540425&partnerID=8YFLogxK

U2 - 10.2337/dc20-2842

DO - 10.2337/dc20-2842

M3 - Article

C2 - 33722880

AN - SCOPUS:85106540425

SN - 0149-5992

VL - 44

SP - 1219

EP - 1227

JO - Diabetes Care

JF - Diabetes Care

IS - 5

ER -

Relation of Lipoprotein(a) Levels to Incident Type 2 Diabetes and Modification by Alirocumab Treatment

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