Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab. Issue 9 (30th June 2022)

• Record Type: Journal Article
• Authors: Hagström, Emil; Steg, P. Gabriel; Szarek, Michael; Bhatt, Deepak L.; Bittner, Vera A.; Danchin, Nicolas; Diaz, Rafael; Goodman, Shaun G.; Harrington, Robert A.; Jukema, J. Wouter; Liberopoulos, Evangelos; Marx, Nikolaus; McGinniss, Jennifer; Manvelian, Garen; Pordy, Robert; Scemama, Michel; White, Harvey D.; Zeiher, Andreas M.; Schwartz, Gregory G.
• Other Names: Schwartz Gregory G. author non-byline.; Bhatt Deepak L. author non-byline.; Bittner Vera A. author non-byline.; Diaz Rafael author non-byline.; Goodman Shaun G. author non-byline.; Harrington Robert A. author non-byline.; Jukema J. Wouter author non-byline.; Szarek Michael author non-byline.; White Harvey D. author non-byline.; Zeiher Andreas M. author non-byline.; Tricoci Pierluigi author non-byline.; Roe Matthew T. author non-byline.; Mahaffey Kenneth W. author non-byline.; Edelberg Jay M. author non-byline.; Hanotin Corinne author non-byline.; Lecorps Guillaume author non-byline.; Moryusef Angèle author non-byline.; Pordy Robert author non-byline.; Sasiela William J. author non-byline.; Tamby Jean-François author non-byline.; Diaz Rafael author non-byline.; Aylward Philip E author non-byline.; Drexel Heinz author non-byline.; Sinnaeve Peter author non-byline.; Dilic Mirza author non-byline.; Lopes Renato D. author non-byline.; Gotcheva Nina N author non-byline.; Goodman Shaun G. author non-byline.; Prieto Juan-Carlos author non-byline.; Yong Huo author non-byline.; López-Jaramillo Patricio author non-byline.; Pećin Ivan author non-byline.; Reiner Zeljko author non-byline.; Ostadal Petr author non-byline.; Poulsen Steen Hvitfeldt author non-byline.; Viigimaa Margus author non-byline.; Nieminen Markku S author non-byline.; Danchin Nicolas author non-byline.; Chumburidze Vakhtang author non-byline.; Marx Nikolaus author non-byline.; Liberopoulos Evangelos author non-byline.; Carlos Pablo author non-byline.; Valdovinos Montenegro author non-byline.; Tse Hung-Fat author non-byline.; Kiss Robert Gabor author non-byline.; Xavier Denis author non-byline.; Zahger Doron author non-byline.; Valgimigli Marco author non-byline.; Kimura Takeshi author non-byline.; Kim Hyo Soo author non-byline.; Kim Sang-Hyun author non-byline.; Erglis Andrejs author non-byline.; Laucevicius Aleksandras author non-byline.; Kedev Sasko author non-byline.; Yusoff Khalid author non-byline.; Ramos López Gabriel Arturo author non-byline.; Alings Marco author non-byline.; White Harvey D. author non-byline.; Halvorsen Sigrun author non-byline.; Correa Flores Roger M author non-byline.; Sy Rody G. author non-byline.; Budaj Andrzej author non-byline.; Morais Joao author non-byline.; Dorobantu Maria author non-byline.; Karpov Yuri author non-byline.; Ristic Arsen D. author non-byline.; Chua Terrance author non-byline.; Murin Jan author non-byline.; Fras Zlatko author non-byline.; Dalby Anthony J author non-byline.; Tuñón José author non-byline.; de Silva H. Asita author non-byline.; Hagström Emil author non-byline.; Landmesser Ulf author non-byline.; Müller Christian author non-byline.; Chiang Chern-En author non-byline.; Sritara Piyamitr author non-byline.; Guneri Sema author non-byline.; Parkhomenko Alexander author non-byline.; Ray Kausik K. author non-byline.; Moriarty Patrick M. author non-byline.; Roe Matthew T. author non-byline.; Vogel Robert author non-byline.; Chaitman Bernard author non-byline.; Kelsey Sheryl F. author non-byline.; Olsson Anders G. author non-byline.; Rouleau Jean-Lucien author non-byline.; Simoons Maarten L. author non-byline.; Alexander Karen author non-byline.; Meloni Chiara author non-byline.; Rosenson Robert author non-byline.; Sijbrands Eric J.G. author non-byline.; Tricoci Pierluigi author non-byline.; Alexander John H. author non-byline.; Armaganijan Luciana author non-byline.; Bagai Akshay author non-byline.; Bahit Maria Cecilia author non-byline.; Brennan J. Matthew author non-byline.; Clifton Shaun author non-byline.; DeVore Adam D. author non-byline.; Deloatch Shalonda author non-byline.; Dickey Sheila author non-byline.; Dombrowski Keith author non-byline.; Ducrocq Grégory author non-byline.; Eapen Zubin author non-byline.; Endsley Patricia author non-byline.; Eppinger Arleen author non-byline.; Harrison Robert W. author non-byline.; Hess Connie Ng author non-byline.; Hlatky Mark A. author non-byline.; Jordan Joseph Dedrick author non-byline.; Knowles Joshua W. author non-byline.; Kolls Bradley J. author non-byline.; Kong David F. author non-byline.; Leonardi Sergio author non-byline.; Lillis Linda author non-byline.; Lopes Renato D. author non-byline.; Maron David J. author non-byline.; Mahaffey Kenneth W. author non-byline.; Marcus Jill author non-byline.; Mathews Robin author non-byline.; Mehta Rajendra H. author non-byline.; Mentz Robert J. author non-byline.; Moreira Humberto Graner author non-byline.; Patel Chetan B. author non-byline.; Pereira Sabrina Bernardez author non-byline.; Perkins Lynn author non-byline.; Povsic Thomas J. author non-byline.; Puymirat Etienne author non-byline.; Roe Matthew T. author non-byline.; Jones William Schuyler author non-byline.; Shah Bimal R. author non-byline.; Sherwood Matthew W. author non-byline.; Stringfellow Kenya author non-byline.; Sujjavanich Darin author non-byline.; Toma Mustafa author non-byline.; Trotter Charlene author non-byline.; van Diepen Sean F.P. author non-byline.; Wilson Matthew D. author non-byline.; Tze-Kay Yan Andrew author non-byline.; Schiavi Lilia B author non-byline.; Garrido Marcelo author non-byline.; Alvarisqueta Andrés F author non-byline.; Sassone Sonia A author non-byline.; Bordonava Anselmo P author non-byline.; Alves De Lima Alberto E author non-byline.; Schmidberg Jorge M author non-byline.; Duronto Ernesto A author non-byline.; Caruso Orlando C author non-byline.; Novaretto Leonardo P author non-byline.; Hominal Miguel Angel author non-byline.; Montaña Oscar R author non-byline.; Caccavo Alberto author non-byline.; Gomez Vilamajo Oscar A author non-byline.; Lorenzatti Alberto J author non-byline.; Cartasegna Luis R author non-byline.; Paterlini Gustavo A author non-byline.; Mackinnon Ignacio J author non-byline.; Caime Guillermo D author non-byline.; Amuchastegui Marcos author non-byline.; Salomone Oscar author non-byline.; Codutti Oscar R author non-byline.; Jure Horacio O author non-byline.; Bono Julio OE author non-byline.; Hrabar Adrian D author non-byline.; Vallejos Julio A author non-byline.; Ahuad Guerrero Rodolfo A author non-byline.; Novoa Federico author non-byline.; Patocchi Cristian A author non-byline.; Zaidman Cesar J author non-byline.; Giuliano Maria E author non-byline.; Dran Ricardo D author non-byline.; Vico Marisa L author non-byline.; Carnero Gabriela S author non-byline.; Guzman Pablo N author non-byline.; Medrano Allende Juan C author non-byline.; Garcia Brasca Daniela F author non-byline.; Bustamante Labarta Miguel H author non-byline.; Nani Sebastian author non-byline.; Blumberg Eduardo DS author non-byline.; Colombo Hugo R author non-byline.; Liberman Alberto author non-byline.; Fuentealba Victorino author non-byline.; Luciardi Hector L author non-byline.; Waisman Gabriel D author non-byline.; Berli Mario A author non-byline.; Garcia Duran Ruben O author non-byline.; Cestari Horacio G author non-byline.; Luquez Hugo A author non-byline.; Giordano Jorge A author non-byline.; Saavedra Silvia S author non-byline.; Zapata Gerardo author non-byline.; Costamagna Osvaldo author non-byline.; Llois Susana author non-byline.; Waites Jonathon H author non-byline.; Collins Nicholas author non-byline.; Soward Allan author non-byline.; Aylward Philip E author non-byline.; Hii Chris LS author non-byline.; Aylward Philip E author non-byline.; Shaw James author non-byline.; Arstall Margaret A author non-byline.; Horowitz John author non-byline.; Ninio Daniel author non-byline.; Rogers James F author non-byline.; Colquhoun David author non-byline.; Oqueli Flores Romulo E author non-byline.; Roberts-Thomson Philip author non-byline.; Raffel Owen author non-byline.; Lehman Sam J author non-byline.; Aroney Constantine author non-byline.; Coverdale Steven GM author non-byline.; Garrahy Paul J author non-byline.; Starmer Gregory author non-byline.; Sader Mark author non-byline.; Carroll Patrick A author non-byline.; Dick Ronald author non-byline.; Zweiker Robert author non-byline.; Hoppe Uta author non-byline.; Drexel Heinz author non-byline.; Huber Kurt author non-byline.; Berger Rudolf author non-byline.; Delle-Karth Georg author non-byline.; Frey Bernhard author non-byline.; Weidinger Franz author non-byline.; Faes Dirk author non-byline.; Hermans Kurt author non-byline.; Pirenne Bruno author non-byline.; Leone Attilio author non-byline.; Hoffer Etienne author non-byline.; Sinnaeve Peter author non-byline.; Vrolix Mathias CM author non-byline.; Wolf Luc De author non-byline.; Wollaert Bart author non-byline.; Castadot Marc author non-byline.; 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Duda Norberto author non-byline.; Kalil Renato author non-byline.; Kormann Adrian author non-byline.; Abrantes José Antonio M author non-byline.; Filho Pedro Pimentel author non-byline.; Soggia Ana Priscila author non-byline.; de Santos Mayler ON author non-byline.; Neuenschwander Fernando author non-byline.; Bodanese Luiz C author non-byline.; Michalaros Yorghos L author non-byline.; Eliaschewitz Freddy G author non-byline.; Vidotti Maria H author non-byline.; Leaes Paulo E author non-byline.; Botelho Roberto V author non-byline.; Kaiser Sergio author non-byline.; Manenti Euler Roberto F Fernandes author non-byline.; Precoma Dalton B author non-byline.; Moura Jorge Jose C author non-byline.; Silva Pedro author non-byline.; Silveira Jose A author non-byline.; Saporito Wladmir author non-byline.; Neto Jose A Marin author non-byline.; Feitosa Gilson S author non-byline.; Ritt Luiz Eduardo F author non-byline.; de Souza Juliana A author non-byline.; Costa Fernando author non-byline.; Souza Weimar KSB author non-byline.; Reis Helder JL author non-byline.; Lopes Renato D. author non-byline.; Machado Leandro author non-byline.; Aidar Ayoub José Carlos author non-byline.; Todorov Georgi V author non-byline.; Nikolov Fedya P author non-byline.; Velcheva Elena S author non-byline.; Tzekova Maria L author non-byline.; Benov Haralambi O author non-byline.; Petranov Stanislav L author non-byline.; Tumbev Haralin S author non-byline.; Shehova-Yankova Nina S author non-byline.; Markov Dimitar T author non-byline.; Raev Dimitar H author non-byline.; Mollov Mihail N author non-byline.; Kichukov Kostadin N author non-byline.; Ilieva- Pandeva Katya A author non-byline.; Gotcheva Nina N author non-byline.; Ivanova Raya author non-byline.; Gospodinov Maryana author non-byline.; Mincheva Valentina M author non-byline.; Lazov Petar V author non-byline.; Dimov Bojidar I author non-byline.; Senaratne Manohara author non-byline.; Stone James author non-byline.; Kornder Jan author non-byline.; Pearce Stephen author non-byline.; 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• Is Part Of: Circulation. Volume 146:Issue 9(2022)
• Page Start: 657
• Page End: 672
• Publication Date: 2022-06-30
• Subjects: acute coronary syndrome -- apolipoproteins B -- cholesterol, LDL -- heart disease risk factors -- PCSK9 inhibitors; Blood -- Circulation -- Periodicals; Cardiovascular system -- Periodicals; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; 616.1
• DOI: 10.1161/CIRCULATIONAHA.121.057807
• Languages: English
• ISSNs: 0009-7322

Abstract

Abstract : Background: Apolipoprotein B (apoB) provides an integrated measure of atherogenic risk. Whether apoB levels and apoB lowering hold incremental predictive information on residual risk after acute coronary syndrome beyond that provided by low-density lipoprotein cholesterol is uncertain. Methods: The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) compared the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin therapy. Primary outcome was major adverse cardiovascular events (MACE; coronary heart disease death, nonfatal myocardial infarction, fatal/nonfatal ischemic stroke, hospitalization for unstable angina). Associations between baseline apoB or apoB at 4 months and MACE were assessed in adjusted Cox proportional hazards and propensity score–matched models. Results: Median follow-up was 2.8 years. In proportional hazards analysis in the placebo group, MACE incidence increased across increasing baseline apoB strata (3.2 [95% CI, 2.9–3.6], 4.0 [95% CI, 3.6–4.5], and 5.5 [95% CI, 5.0–6.1] events per 100 patient-years in strata <75, 75–<90, ≥90 mg/dL, respectively; P trend <0.0001) and after adjustment for low-density lipoprotein cholesterol ( P trend =0.035). Higher baseline apoB stratum was associated with greater relative ( P trend <0.0001) and absolute reduction in MACE with alirocumab versus placebo. In the alirocumab group, the incidence of MACE after month 4 decreased monotonically across decreasing achieved apoB strata (4.26 [95% CI, 3.78–4.79], 3.09 [95% CI, 2.69–3.54], and 2.41 [95% CI, 2.11–2.76] events per 100 patient-years in strata ≥50, >35–<50, and ≤35 mg/dL, respectively). Compared with propensity score–matched patients from the placebo group, treatment hazard ratios for alirocumab also decreased monotonically across achieved apoB strata. Achieved apoB was predictive of MACE after adjustment for achieved low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol but not vice versa. Conclusions: In patients with recent acute coronary syndrome and elevated atherogenic lipoproteins, MACE increased across baseline apoB strata. Alirocumab reduced MACE across all strata of baseline apoB, with larger absolute reductions in patients with higher baseline levels. Lower achieved apoB was associated with lower risk of MACE, even after accounting for achieved low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol, indicating that apoB provides incremental information. Achievement of apoB levels as low as ≤35 mg/dL may reduce lipoprotein-attributable residual risk after acute coronary syndrome. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01663402.