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Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Title: Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial
Authors: Steg, PG; Szarek, M; Bhatt, DL; Bittner, VA; Bregeault, M-F; Dalby, AJ; Diaz, R; Edelberg, JM; Goodman, SG; Hanotin, C; Harrington, RA; Jukema, JW; Lecorps, G; Mahaffey, KW; Moryusef, A; Ostadal, P; Parkhomenko, A; Pordy, R; Roe, MT; Tricoci, P; Vogel, R; White, HD; Zeiher, AM; Schwartz, GG; Sasiela, WJ; Tamby, J-F; Aylward, PE; Drexel, H; Sinnaeve, P; Dilic, M; Gotcheva, NN; Prieto, J-C; Yong, H; Lopez-Jaramillo, P; Pecin, I; Reiner, Z; 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, HS; Kim, S-H; Kedev, S; Erglis, A; Laucevicius, A; Yusoff, K; Lopez, R; Ramos Lopez, GA; Alings, M; Halvorsen, S; Correa Flores, RM; Sy, RG; Budaj, A; Morais, J; Dorobantu, M; Karpov, Y; Ristic, AD; Chua, T; Murin, J; Fras, Z; Tunon, J; De Silva, HA; Hagstrom, E; Muller, C; Chiang, C-E; Sritara, P; Guneri, S; Ray, KK; Moriarty, PM; Chaitman, B; Kelsey, SF; Olsson, AG; Rouleau, J-L; Simoons, ML; Alexander, K; Meloni, C; Rosenson, R; Sijbrands, EJG; Alexander, JH; Armaganijan, L; Bagai, A; Bahit, MC; 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; Kong, DF; Leonardi, S; Lillis, L; Maron, DJ; Marcus, J; Mathews, R; Mehta, RH; Mentz, RJ; Moreira, HG; Patel, CB; Pereira, SB; Perkins, L; Povsic, TJ; Puymirat, E; Jones, WS; Shah, BR; Sherwood, MW; Stringfellow, K; Sujjavanich, D; Toma, M; Van Diepen, SFP; Wilson, MD; Yan, AT-K; Lopes, RD; Trotter, C; Schiavi, LB; Garrido, M; Alvarisqueta, AF; Sassone, SA; Bordonava, AP; Alves De Lima, AE; Schmidberg, JM; Duronto, EA; Caruso, OC; Novaretto, LP; Angel Hominal, M; Montana, OR; Caccavo, A; Gomez Vilamajo, OA; Lorenzatti, AJ; Cartasegna, LR; Paterlini, GA; Mackinnon, IJ; Caime, GD; Amuchastegui, M; Salomone, R; Codutti, OR; Jure, HO; Bono, JOE; Hrabar, AD; Vallejos, JA; Ahuad Guerrero, RA; Novoa, F; Patocchi, CA; Zaidman, CJ; Giuliano, ME; Dran, RD; Vico, ML; Carnero, GS; Guzman, PN; Medrano Allende, JC; Garcia Brasca, DF; Bustamante Labarta, MH; Nani, S; Blumberg, EDS; Colombo, HR; Liberman, A; Luciardi, HL; Waisman, GD; Berli, MA; Duran, ROG; Cestari, HG; Luquez, HA; Giordano, JA; Saavedra, SS; Zapata, G; Costamagna, O; Llois, S; Waites, JH; Collins, N; Soward, A; Hii, CLS; Shaw, J; Arstall, MA; Horowitz, J; Rogers, JF; Colquhoun, D; Oqueli Flores, RE; Roberts-Thomson, P; Raffel, O; Lehman, SJ; Aroney, C; Coverdale, SGM; Garrahy, PJ; Starmer, G; Sader, M; Carroll, PA; Dick, R; Zweiker, R; Hoppe, U; Huber, K; Berger, R; Weidinger, F; Faes, D; Hermans, K; Pirenne, B; Leone, A; Hoffer, E; 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; Durak-Nalbantic, A; Vulic, D; Muslibegovic, A; Goronja, B; Reis, G; Sousa, L; Nicolau, JC; Giorgeto, FE; Silva, RP; Maia, LN; Rech, R; Rossi, PRF; Cerqueira, MJAG; Duda, N; Kalil, R; Kormann, A; Abrantes, JAM; Pimentel Filho, P; Soggia, AP; De Santos, MON; Neuenschwander, F; Bodanese, LC; Michalaros, YL; Eliaschewitz, FG; Vidotti, MH; Leaes, PE; Botelho, RV; Kaiser, S; Fernandes Manenti, ERF; Precoma, DB; Moura Jorge, JC; Silva, PGMDB; Silveira, JA; Saporito, W; Marin Neto, JA; Feitosa, GS; Ritt, LEF; De Souza, JA; Costa, F; Souza, WKSB; Reis, HJL; Machado, L; Aidar Ayoub, JC; Todorov, GV; Nikolov, FP; Velcheva, ES; Tzekova, ML; Benov, HO; Petranov, SL; Tumbev, HS; Shehova-Yankova, NS; Markov, DT; Raev, DH; Mollov, MN; Kichukov, KN; Ilieva-Pandeva, KA; Ivanova, R; Mincheva, VM; Lazov, PV; Dimov, BI; Senaratne, M; Stone, J; Kornder, J; Pearce, S; Dion, D; Savard, D; Pesant, Y; Pandey, A; Robinson, S; Gosselin, G; Vizel, S; Hoag, G; Bourgeois, R; Morisset, A; Sabbah, E; Sussex, B; Kouz, S; MacDonald, P; Diaz, A; Michaud, N; Fell, D; 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Silva, SIB; Lozada, HJG; Arroyo, JAC; Mendoza, JLA; Ruiz, RLF; Jatin, FGM; Herazo, AS; Parada, JC; Triana, MAU; Strozzi, M; Car, S; Milicic, D; Bencic, ML; Pintaric, H; Prvulovic, D; Sikic, J; Persic, V; Mileta, D; Stambuk, K; Zdravko, B; Tomulic, V; Krstulovic, SM; Starcevic, B; Spinar, J; Horak, D; Stasek, J; Alan, D; Machova, V; Linhart, A; Novotny, V; Kaucak, V; Rokyta, R; Naplava, R; Coufal, Z; Adamkova, V; Podpera, I; Zizka, J; Motovska, Z; Marusincova, I; Svab, P; Heinc, P; Kuchar, J; Povolny, P; Matuska, J; Raungaard, B; Clemmensen, P; Bang, LE; May, O; Bottcher, M; Hove, JD; Frost, L; Gislason, G; Larsen, J; Johansen, PB; Hald, F; Jeppesen, J; Nielsen, T; Kristensen, KS; Walichiewicz, PM; Lomholdt, JD; Klausen, IC; Nielsen, PK; Davidsen, F; Videbaek, L; Soots, M; Vahula, V; Hedman, A; Soopold, U; Martsin, K; Kristjan, A; Taskinen, M-R; Porthan, K; Airaksinen, JK; Juonala, M; Kiviniemi, T; Vikman, S; Posio, P; Taurio, J; Huikuri, H; Kaikkonen, K; Coste, P; Ferrari, E; Morel, O; 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Source: 112 ; 103
Publisher Information: American Heart Association
Publication Year: 2019
Collection: Imperial College London: Spiral
Subject Terms: Science & Technology; Life Sciences & Biomedicine; Cardiac & Cardiovascular Systems; Peripheral Vascular Disease; Cardiovascular System & Cardiology; acute coronary syndrome; alirocumab; cholesterol; mortality; PCSK9 protein; MONOCLONAL-ANTIBODY; REDUCING LIPIDS; EFFICACY; SAFETY; EVOLOCUMAB; PCSK9; Aged; Antibodies; Monoclonal; Humanized; LDL; Double-Blind Method; Drug Therapy; Combination; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Injections
Description: Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P
Document Type: article in journal/newspaper
Language: English
Relation: Circulation; http://hdl.handle.net/10044/1/78701
DOI: 10.1161/CIRCULATIONAHA.118.038840
Availability: http://hdl.handle.net/10044/1/78701; https://doi.org/10.1161/CIRCULATIONAHA.118.038840
Rights: © 2019 The Authors. Circulation is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.
Accession Number: edsbas.1C4C949A
Database: BASE