Effect of Alirocumab on Mortality After Acute Coronary Syndromes An Analysis of the ODYSSEY OUTCOMES Randomized Clinical Trial

Philippe Gabriel Steg; Michael Szarek; Deepak L Bhatt; Vera A Bittner; Marie-France Bregeault; Anthony J Dalby; Rafael Diaz; Jay M Edelberg; Shaun G Goodman; Corinne Hanotin; Robert A Harrington; J Wouter Jukema; Guillaume Lecorps; Kenneth W Mahaffey; Angele Moryusef; Petr Ostadal; Alexander Parkhomenko; Robert Pordy; Matthew T Roe; Pierluigi Tricoci; Robert Vogel; Harvey D White; Andreas M Zeiher; Gregory G Schwartz; William J Sasiela; Jean-Francois Tamby; Philip E Aylward; Heinz Drexel; Peter Sinnaeve; Mirza Dilic; Nina N Gotcheva; Juan-Carlos Prieto; Huo Yong; Patricio Lopez-Jaramillo; Ivan Pecin; Zeljko Reiner; 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; Sasko Kedev; Andrejs Erglis; Aleksandras Laucevicius; Khalid Yusoff; Ramos Lopez; Gabriel Arturo Ramos Lopez; Marco Alings; Sigrun Halvorsen; Roger M Correa Flores; Rody G Sy; Andrzej Budaj; Joao Morais; Maria Dorobantu; Yuri Karpov; Arsen D Ristic; Terrance Chua; Jan Murin; Zlatko Fras; Jose Tunon; H Asita de Silva; Emil Hagstrom; Christian Muller; Chern-En Chiang; Piyamitr Sritara; Sema Guneri; Kausik K Ray; Patrick M Moriarty; Bernard Chaitman; Sheryl F Kelsey; Anders G Olsson; Jean-Lucien Rouleau; Maarten L Simoons; Karen Alexander; Chiara Meloni; Robert Rosenson; Eric JG Sijbrands; John H Alexander; Luciana Armaganijan; Akshay Bagai; Maria Cecilia Bahit; J Matthew Brennan; Shaun Clifton; Adam D DeVore; Shalonda Deloatch; Sheila Dickey; Keith Dombrowski; Gregory 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; David F Kong; Sergio Leonardi; Linda Lillis; David J Maron; 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; William Schuyler Jones; Bimal R Shah; Matthew W Sherwood; Kenya Stringfellow; Darin Sujjavanich; Mustafa Toma; Sean FP Van Diepen; Matthew D Wilson; Andrew Tze-Kay Yan; Renato D Lopes; Charlene Trotter; Lilia B Schiavi; Marcelo Garrido; Andres F Alvarisqueta; Sonia A Sassone; Anselmo P Bordonava; Alberto E Alves De Lima; Jorge M Schmidberg; Ernesto A Duronto; Orlando C Caruso; Leonardo P Novaretto; Miguel Angel Hominal; Oscar R Montana; Alberto Caccavo; Oscar A Gomez Vilamajo; Alberto J Lorenzatti; Luis R Cartasegna; Gustavo A Paterlini; Ignacio J Mackinnon; Guillermo D Caime; Marcos Amuchastegui; Rodolfo Salomone; Oscar R Codutti; Horacio O Jure; Julio OE Bono; Adrian D Hrabar; Julio A Vallejos; Rodolfo A Ahuad Guerrero; Federico Novoa; Cristian A Patocchi; Cesar J Zaidman; Maria E Giuliano; Ricardo D Dran; Marisa L 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; Alberto Liberman; Hector L Luciardi; Gabriel D Waisman; Mario A Berli; Ruben O Garcia Duran; Horacio G Cestari; Hugo A Luquez; Jorge A Giordano; Silvia S Saavedra; Gerardo Zapata; Osvaldo Costamagna; Susana Llois; Jonathon H Waites; Nicholas Collins; Allan Soward; Chris LS Hii; James Shaw; Margaret A Arstall; John Horowitz; James F Rogers; David Colquhoun; Romulo E Oqueli Flores; Philip Roberts-Thomson; Owen Raffel; Sam J Lehman; Constantine Aroney; Steven GM Coverdale; Paul J Garrahy; Gregory Starmer; Mark Sader; Patrick A Carroll; Ronald Dick; Robert Zweiker; Uta Hoppe; Kurt Huber; Rudolf Berger; Franz Weidinger; Dirk Faes; Kurt Hermans; Bruno Pirenne; Attilio Leone; Etienne Hoffer; 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; Azra Durak-Nalbantic; Dusko Vulic; Adis Muslibegovic; Boris Goronja; Gilmar Reis; Luciano Sousa; Jose C Nicolau; Flavio E Giorgeto; Ricardo P Silva; Lilia Nigro Maia; Rafael Rech; Paulo RF Rossi; Maria Jose AG Cerqueira; Norberto Duda; Renato Kalil; Adrian Kormann; Jose Antonio M Abrantes; Pedro Pimentel Filho; Ana Priscila Soggia; Mayler ON de Santos; Fernando Neuenschwander; Luiz C Bodanese; Yorghos L Michalaros; Freddy G Eliaschewitz; Maria H Vidotti; Paulo E Leaes; Roberto V Botelho; Sergio Kaiser; Euler Roberto F Fernandes Manenti; Dalton B Precoma; Jose C Moura Jorge; Pedro GM de B Silva; Jose A Silveira; Wladmir Saporito; Jose A Marin Neto; Gilson S Feitosa; Luiz Eduardo F Ritt; Juliana A de Souza; Fernando Costa; Weimar KSB Souza; Helder JL Reis; Leandro Machado; Jose Carlos Aidar Ayoub; Georgi V Todorov; Fedya P Nikolov; Elena S Velcheva; Maria L Tzekova; Haralambi O Benov; Stanislav L Petranov; Haralin S Tumbev; Nina S Shehova-Yankova; Dimitar T Markov; Dimitar H Raev; Mihail N Mollov; Kostadin N Kichukov; Katya A Ilieva-Pandeva; Raya Ivanova; Valentina M Mincheva; Petar V Lazov; Bojidar I Dimov; Manohara Senaratne; James Stone; Jan Kornder; Stephen Pearce; Danielle Dion; Daniel Savard; Yves Pesant; Amritanshu Pandey; Simon Robinson; Gilbert Gosselin; Saul Vizel; Gordon Hoag; Ronald Bourgeois; Anne Morisset; Eric Sabbah; Bruce Sussex; Simon Kouz; Paul MacDonald; Ariel Diaz; Nicolas Michaud; David Fell; Raymond Leung; Tycho Vuurmans; Christopher Lai; Frank Nigro; Richard Davies; Gustavo Nogareda; Ram Vijayaraghavan; John Ducas; Serge Lepage; Shamir Mehta; James Cha; Robert Dupuis; Peter Fong; Josep Rodes-Cabau; Hussein Fadlallah; David Cleveland; Huynh Thao; Iqbal Bata; Adnan Hameed; Cristian Pincetti; Sergio Potthoff; Juan C Prieto; Monica Acevedo; Arnoldo Aguirre; Margarita Vejar; Mario Yanez; Guillermo Araneda; Mauricio Fernandez; Luis Perez; Paola Varleta; Fernando Florenzano; Laura Huidobro; Carlos A Raffo; Claudia Olivares; Leonardo Nahuelpan; Humberto Montecinos; Jiyan Chen; Yugang Dong; Weijian Huang; Jianzhong Wang; Shi'An Huang; Zhuhua Yao; Xiang Li; Lan Cui; Wenhua Lin; Yuemin Sun; Jingfeng Wang; Jianping Li; Xuelian Zhang; Hong Zhu; Dandan Chen; Lan Huang; Shaohong Dong; Guohai Su; Biao Xu; Xi Su; Xiaoshu Cheng; Jinxiu Lin; Wenxia Zong; Huanming Li; Yi Feng; Dingli Xu; Xinchun Yang; Yuannan Ke; Xuefeng Lin; Zheng Zhang; Zeqi Zheng; Zhurong Luo; Yundai Chen; Chunhua Ding; Yang Zheng; Xiaodong Li; Daoquan Peng; Ying Li; Meng Wei; Shaowen Liu; Yihua Yu; Baiming Qu; Weihong Jiang; Yujie Zhou; Xingsheng Zhao; Zuyi Yuan; Ying Guo; Xiping Xu; Xubo Shi; Junbo Ge; Guosheng Fu; Feng Bai; Weiyi Fang; Xiling Shou; Xiangjun Yang; Jian'An Wang; Yingxian Sun; Qinghua Lu; Ruiyan Zhang; Jianhua Zhu; Yizhou Xu; Zhongcai Fan; Tianchang Li; Chun Wu; Nicolas Jaramillo; Gregorio Sanchez Vallejo; Diana C Luna Botia; Rodrigo Botero Lopez; Dora I Molina De Salazar; Alberto J Cadena Bonfanti; Juan Diego Higuera; Sandra I Barrera Silva; Henry J Garcia Lozada; Julian A Coronel Arroyo; Jose L Accini Mendoza; Ricardo L Fernandez Ruiz; Fernando G Manzur Jatin; Aristides Sotomayor Herazo; Jeffrey Castellanos Parada; Miguel A Urina Triana; Maja Strozzi; Sinisa Car; Davor Milicic; Martina Lovric Bencic; Hrvoje Pintaric; Deiti Prvulovic; Jozica Sikic; Viktor Persic; Dean Mileta; Kresimir Stambuk; Babic Zdravko; Vjekoslav Tomulic; Stanka Mejic Krstulovic; Boris Starcevic; Jindrich Spinar; David Horak; Josef Stasek; David Alan; Vilma Machova; Ales Linhart; Vojtech Novotny; Vladimir Kaucak; Richard Rokyta; Robert Naplava; Zdenek Coufal; Vera Adamkova; Ivo Podpera; Jiri Zizka; Zuzana Motovska; Ivana Marusincova; Premysl Svab; Petr Heinc; Jiri Kuchar; Petr Povolny; Jiri Matuska; Bent Raungaard; Peter Clemmensen; Lia E Bang; Ole May; Morten Bottcher; Jens D Hove; Lars Frost; Gunnar Gislason; John Larsen; Peter Betton Johansen; Flemming Hald; Jorgen Jeppesen; Tonny Nielsen; Kjeld S Kristensen; Piotr Maria Walichiewicz; Jens D Lomholdt; Ib C Klausen; Peter Kaiser Nielsen; Flemming Davidsen; Lars Videbaek; Mai Soots; Veiko Vahula; Anu Hedman; Ullar Soopold; Kaja Martsin; Arved Kristjan; Marja-Riitta Taskinen; Kimmo Porthan; Juhani K Airaksinen; Markus Juonala; Tuomas Kiviniemi; Saila Vikman; Pirjo Posio; Jyrki Taurio; Heikki Huikuri; Kari Kaikkonen; Pierre Coste; Emile Ferrari; Olivier Morel; Gilles Montalescot; Gilles Barone-Rochette; Jacques Mansourati; Yves Cottin; Florence Leclercq; Abdelkader Belhassane; Nicolas Delarche; Franck Boccara; Franck Paganelli; Jerome Clerc; Francois Schiele; Victor Aboyans; Vincent Probst; Jacques Berland; Thierry Lefevre; Bernard Citron; Irakli Khintibidze; Tamaz Shaburishvili; Zurab Pagava; Ramaz Ghlonti; Zaza Lominadze; George Khabeishvili; Rayyan Hemetsberger; Ursula Rauch-Kroehnert; Matthias Stratmann; Karl-Friedrich Appel; Ekkehard Schmidt; Heyder Omran; Christoph Stellbrink; Thomas Dorsel; Emmanouil Lianopoulos; Roger Marx; Andreas Zirlik; Detlev Schellenberg; Thomas Heitzer; Ulrich Laufs; Stephan Gielen; Bernhard Winkelmann; Steffen Behrens; Karsten Sydow; Gregor Simonis; Thomas Muenzel; Nikos Werner; Stefan Leggewie; Dirk Boecker; Ruediger Braun-Dullaeus; Nicole Toursarkissian; Michael Jeserich; Matthias Weissbrodt; Tim Schaeufele; Joachim Weil; Heinz Voeller; Johannes Waltenberger; Mohammed Natour; Susanne Schmitt; Stephan Steiner; Lothar Heidenreich; Uwe Gremmler; Holger Killat; Werner Rieker; Sotiris Patsilinakos; Athanasios Kartalis; Athanassios Manolis; Dimitrios Sionis; Ioannis Skoumas; Vasilios Athyros; Panagiotis Vardas; Frangkiskos Parthenakis; Dimitrios Alexopoulos; Georgios Hahalis; John Lekakis; Apostolos Hatzitolios; Sergio R Fausto Ovando; Juan L Arango Benecke; Edgar R Rodriguez De Leon; Bryan PY Yan; David CW Siu; Tibor Turi; Bela Merkely; Imre Ungi; Geza Lupkovics; Lajos Nagy; Andras Katona; Istvan Edes; Gabor Muller; Ivan Horvath; Tibor Kapin; Jozsef Falukozy; Mukund Kumbla; Manjinder Sandhu; Sharath Annam; Naveen Reddy Proddutur; Rajendra K Premchand; Ajaykumar Mahajan; Atul D Abhyanakar; Prafulla Kerkar; Ravishankar A Govinda; Abraham Oomman; Dhurjati Sinha; Sachin N Patil; Dhiman Kahali; Jitendra Sawhney; Abhijeet B Joshi; Sanjeev Chaudhary; Pankaj Harkut; Santanu Guha; Sanjay Porwal; Srimannarayana Jujjuru; Ramesh B Pothineni; Minguel R Monteiro; Aziz Khan; Shamanna S Iyengar; Jasprakash Singh Grewal; Manoj Chopda; Mahesh C Fulwani; Aparna Patange; Vijay K Chopra; Naresh K Goyal; Rituparna Shinde; Gajendra V Manakshe; Nitin Patki; Sumeet Sethi; Vengatesh Munusamy; Sunil Karna; Srilakshmi Adhyapak; Ulhas Pandurangi; Rishabh Mathur; Suhas Kalashetti; Ajit Bhagwat; Bagirath Raghuraman; Shiv Kumar Yerra; Prasant Bhansali; Rohidas Borse; Srihari Das; Jabir Abdullakutty; Shireesh Saathe; Priya Palimkar; Jabir Abdullkutty; Shireesh Sathe; Shaul Atar; Michael Shechter; Morris Mosseri; Yaron Arbel; Chaim Lotan; Uri Rosenschein; Amos Katz; Yaakov Henkin; Adi Francis; Marc Klutstein; Eugenia Nikolsky; Yoav Turgeman; Majdi Halabi; Ran Kornowski; Michael Jonas; Offer Amir; Yoseph Rozenman; Shmuel Fuchs; Osamah Hussein; Dov Gavish; Zvi Vered; Yoseph Caraco; Mazen Elias; Naveh Tov; Michael Lishner; Nizar Elias; Giancarlo Piovaccari; Annamaria De Pellegrin; Gabriele Guardigli; Giovanni Licciardello; Carla Auguadro; Claudio Cuccia; Alessandro Salvioni; Giuseppe Musumeci; Paolo Calabro; Salvatore Novo; Pompilio Faggiano; Nicoletta B De Cesare; Sergio Berti; Claudio Cavallini; Enrico Puccioni; Marcello Galvani; Maurizio Tespili; Piermarco Piatti; Michela Palvarini; Giuseppe De Luca; Roberto Violini; Alessandro De Leo; Pasquale Perrone Filardi; Maurizio Ferratini; Vittorio Ricca; Kazuoki Dai; Haruo Kamiya; Kenji Ando; Yoshihiro Takeda; Yoshihiro Morino; Yoshiki Hata; Kazuo Kimura; Koichi Kishi; Ichiro Michishita; Hiroki Uehara; Toshinori Higashikata; Atsushi Hirayama; Keiji Hirooka; Satoru Sakagami; Shuichi Taguchi; Akihiro Koike; Hiroyuki Fujinaga; Shinji Koba; Ken Kozuma; Tomohiro Kawasaki; Yujiro Ono; Masatoshi Shimizu; Yousuke Katsuda; Atsuyuki Wada; Toshiro Shinke; Junya Ako; Kenshi Fujii; Toshiyuki Takahashi; Tomohiro Sakamoto; Yutaka Furukawa; Hiroshi Sugino; Toshiaki Mano; Noriaki Utsu; Kashima Ito; Takuya Haraguchi; Yasunori Ueda; Akira Nishibe; Kazuteru Fujimoto; Motomaru Masutani; Jung Han Yoon; Hun Sik Park; In-Ho Chae; Moo Hyun Kim; Myung Ho Jeong; Seungwoon Rha; Chongjin Kim; Hyo-Soo Kim; Taekjong Hong; Seung-Jea Tahk; Youngkwon Kim; Arija Busmane; Natalija Pontaga; Aldis Strelnieks; Iveta Mintale; Iveta Sime; Zaneta Petrulioniene; Roma Kavaliauskiene; Ruta Jurgaitiene; Gintare Sakalyte; Rimvydas Slapikas; Sigute Norkiene; Nerijus Misonis; Aleksandras Kibarskis; Raimondas Kubilius; Stojko Bojovski; Nensi Lozance; Aleksandar Kjovkaroski; Snezana Doncovska; Tiong Kiam Ong; Sazzli Kasim; Oteh Maskon; Balachandran Kandasamy; Houng B Liew; Wan Mohd Izani Wan Mohamed; Armando Garcia Castillo; Jorge Carrillo Calvillo; Pedro Fajardo Campos; Juan Carlos Nunez Fragoso; Edmundo Alfredo Bayram Llamas; Marco Antonio Alcocer Gamba; Jaime Carranza Madrigal; Luis Gerardo Gonzalez Salas; Enrique Lopez Rosas; Belinda Gonzalez Diaz; Eduardo Salcido Vazquez; Alfredo Nacoud Ackar; Guillermo Antonio Llamas Esperon; Carlos Rodolfo Martinez Sanchez; Maria Guerrero De Leon; Rodrigo Suarez Otero; Guillermo Fanghanel Salmon; Jesus Antonio Perez Rios; Jose Angel Garza Ruiz; Robert W Breedveld; Pieter AM Hoogslag; Harry Suryapranata; Antonius Oomen; Jacobijne J Wiersma; Ruud MA Van Der Wal; Pascalle S Hooft Van Huysduynen-Monraats; Ioannis Karalis; Gerardus JE Verdel; Bart RG Brueren; Roland PTh Troquay; Eric P Viergever; Nadea YY Al-Windy; Gerard L Bartels; Jan H Cornel; Walter RM Hermans; Johannes PR Herrman; Robert J Bos; Reginald GEJ Groutars; Coenraad C Van Der Zwaan; Refik Kaplan; Eelko Ronner; Bjorn E Groenemeijer; Patrick NA Bronzwaer; Anho AH Liem; Bernard JWM Rensing; Marcel JJA Bokern; Remco Nijmeijer; Ferry MRJ Hersbach; Frank F Willems; Antonius TM Gosselink; John Elliott; Gerard Wilkins; Raewyn Fisher; Douglas Scott; Hamish Hart; Ralph Stewart; Scott Harding; Ian Ternouth; Nicholas Fisher; Denise Aitken; Russell Anscombe; Laura Davidson; Tadeusz Tomala; Ottar Nygard; Jon Arne Sparby; Kjell Andersen; Lars Gullestad; Jarle Jortveit; Peter S Munk; Erlend Gyllensten Singsaas; Ulf Hurtig; Jorge R Calderon Ticona; Julio R Durand Velasquez; Sandra A Negron Miguel; Enrique S Sanabria Perez; Jesus M Carrion Chambilla; Carlos A Chavez Ayala; Reynaldo P Castillo Leon; Rolando J Vargas Gonzales; Jose D Hernandez Zuniga; Luis A Camacho Cosavalente; Jorge E Bravo Mannucci; Javier Heredia Landeo; Nassip C Llerena Navarro; Yudy M Roldan Concha; V-ctor E Rodriguez Chavez; Henry A Anchante Hernandez; Carlos A Zea Nunez; Walter Mogrovejo Ramos; Arthur Ferrolino; Rosa Allyn G Sy; Louie Tirador; Generoso Matiga; Raul Martin Coching; Alisa Bernan; Gregorio Rogelio; Dante D Morales; Edgar Tan; Dennis Jose Sulit; Adrian Wlodarczak; Krystyna Jaworska; Grzegorz Skonieczny; Lidia Pawlowicz; Pawel Wojewod; Benita Busz-Papiez; 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Alexander Gordienko; Konstantin Zrazhevsky; Alexander Y Vishnevsky; Victor Gurevich; Raisa Stryuk; Nikita V Lomakin; Igor Bokarev; Sergey Shalaev; Larisa Khaisheva; Petr Chizhov; Inna Viktorova; Natalya Osokina; Evgenia Akatova; Galina Chumakova; Igor Libov; Mikhail I Voevoda; Tatyana V Tretyakova; Evgeny Baranov; Sergey Shustov; Sergey Yakushin; Ivan Gordeev; Niiaz Khasanov; Olga Reshetko; Tatiana Sotnikova; Olga Molchanova; Konstantin Nikolaev; Liudmila Gapon; Elena Baranova; Zaur Shogenov; Elena Kosmachova; Yuriy Karpov; Anton Povzun; Liudmila Egorova; Vadim V Tyrenko; Igor G Ivanov; Sergey Kanorsky; Dragan Simic; Nikola Ivanovic; Goran Davidovic; Nebojsa Tasic; Milika R Asanin; Stevo Stojic; Svetlana R Apostolovic; Stevan Ilic; Biljana Putnikovic; Aleksandar Stankovic; Aleksandra Arandjelovic; Slavica Radovanovic; Jovan Balinovac; Dragan V Dincic; Petar Seferovic; Slobodan Dodic; Sinisa Dimkovic; Kian-Keong Poh; Hean Yee Ong; Karol Micko; Jan Nociar; Daniel Pella; Peter Fulop; Marian Hranai; 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I-Chang Hsieh; Wei Hsiang Lin; Jen-Yuan Kuo; Tsuei-Yuan Huang; Chih-Yuan Fang; Pinij Kaewsuwanna; Wasant Soonfuang; Woravut Jintapakorn; Apichard Sukonthasarn; Nattawut Wongpraparut; Krisada Sastravaha; Nakarin Sansanayudh; Wirash Kehasukcharoen; Dilok Piyayotai; Paiboon Chotnoparatpat; Ahmet Camsari; Hakan Kultursay; Bulent Mutlu; Murat Ersanli; Mustafa Demirtas; Cevat Kirma; Ertan Ural; Lale Koldas; Oleksandr Karpenko; Alexander Prokhorov; Ihor Vakaluyk; Halyna Myshanych; Dmytro Reshotko; Valeriy Batushkin; Leonid Rudenko; Ihor Kovalskyi; Mykola Kushnir; Vira Tseluyko; Yuriy Mostovoy; Mykola Stanislavchuk; Yulian Kyiak; Yuriy Karpenko; Yaroslav Malynovsky; Andriy Klantsa; Oles Kutniy; Ekaterina Amosova; Viktor Tashchuk; Oleh Leshchuk; Mykola Rishko; Mykola Kopytsya; Andriy Yagensky; Mykola Vatutin; Andriy Bagriy; Olga M Barna; Olexiy Ushakov; Georgiy Dzyak; Borys Goloborodko; Anatolii Rudenko; Volodymyr Zheleznyy; Jasper Trevelyan; Azfar Zaman; Kaeng Lee; Andrew Moriarty; Rajesh K Aggarwal; 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doi:10.1161/CIRCULATIONAHA.118.038840

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Effect of Alirocumab on Mortality After Acute Coronary Syndromes An Analysis of the ODYSSEY OUTCOMES Randomized Clinical Trial

Journal article

Peer reviewed

Effect of Alirocumab on Mortality After Acute Coronary Syndromes An Analysis of the ODYSSEY OUTCOMES Randomized Clinical Trial

Philippe Gabriel Steg, Michael Szarek, Deepak L Bhatt, Vera A Bittner, Marie-France Bregeault, Anthony J Dalby, Rafael Diaz, Jay M Edelberg, Shaun G Goodman, Corinne Hanotin, …

07/09/2019

DOI: https://doi.org/10.1161/CIRCULATIONAHA.118.038840

Abstract

acute coronary syndrome

alirocumab

Cardiac & Cardiovascular Systems

Cardiovascular System & Cardiology

cholesterol

EFFICACY

EVOLOCUMAB

Life Sciences & Biomedicine

MONOCLONAL-ANTIBODY

mortality

PCSK9

PCSK9 protein

Peripheral Vascular Disease

REDUCING LIPIDS

SAFETY

Science & Technology

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<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events ( P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined with achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). CONCLUSIONS: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01663402. status: published

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Title: Effect of Alirocumab on Mortality After Acute Coronary Syndromes An Analysis of the ODYSSEY OUTCOMES Randomized Clinical Trial
Creators: Philippe Gabriel Steg - Assistance Publique – Hôpitaux de Paris
Michael Szarek - SUNY Downstate Medical Center
Deepak L Bhatt - Brigham and Women's Hospital
Vera A Bittner - University of Alabama at Birmingham
Marie-France Bregeault - Sanofi
Anthony J Dalby - Milpark Hospital
Rafael Diaz - Instituto Cardiovascular de Rosario
Jay M Edelberg - Sanofi
Shaun G Goodman - University of Alberta
Corinne Hanotin - Sanofi
Robert A Harrington - Center for Clinical Research
J Wouter Jukema - Leiden University Medical Center
Guillaume Lecorps - Sanofi
Kenneth W Mahaffey - Center for Clinical Research
Angele Moryusef - Sanofi
Petr Ostadal - Na Homolce Hospital
Alexander Parkhomenko - Institute of Cardiology, Kyiv, Ukraine (A.P.).
Robert Pordy - Regeneron
Matthew T Roe - Duke University
Pierluigi Tricoci - Duke University
Robert Vogel - University of Colorado Denver
Harvey D White - Auckland City Hospital
Andreas M Zeiher - Goethe University Frankfurt
Gregory G Schwartz - University of Colorado Denver
William J Sasiela
Jean-Francois Tamby
Philip E Aylward
Heinz Drexel
Peter Sinnaeve
Mirza Dilic
Nina N Gotcheva
Juan-Carlos Prieto
Huo Yong
Patricio Lopez-Jaramillo
Ivan Pecin
Zeljko Reiner
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
Sasko Kedev
Andrejs Erglis
Aleksandras Laucevicius
Khalid Yusoff
Ramos Lopez
Gabriel Arturo Ramos Lopez
Marco Alings
Sigrun Halvorsen
Roger M Correa Flores
Rody G Sy
Andrzej Budaj
Joao Morais
Maria Dorobantu
Yuri Karpov
Arsen D Ristic
Terrance Chua
Jan Murin
Zlatko Fras
Jose Tunon
H Asita de Silva
Emil Hagstrom
Christian Muller
Chern-En Chiang
Piyamitr Sritara
Sema Guneri
Kausik K Ray
Patrick M Moriarty
Bernard Chaitman
Sheryl F Kelsey
Anders G Olsson
Jean-Lucien Rouleau
Maarten L Simoons
Karen Alexander
Chiara Meloni
Robert Rosenson
Eric JG Sijbrands
John H Alexander
Luciana Armaganijan
Akshay Bagai
Maria Cecilia Bahit
J Matthew Brennan
Shaun Clifton
Adam D DeVore
Shalonda Deloatch
Sheila Dickey
Keith Dombrowski
Gregory 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
David F Kong
Sergio Leonardi
Linda Lillis
David J Maron
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
William Schuyler Jones
Bimal R Shah
Matthew W Sherwood
Kenya Stringfellow
Darin Sujjavanich
Mustafa Toma
Sean FP Van Diepen
Matthew D Wilson
Andrew Tze-Kay Yan
Renato D Lopes
Charlene Trotter
Lilia B Schiavi
Marcelo Garrido
Andres F Alvarisqueta
Sonia A Sassone
Anselmo P Bordonava
Alberto E Alves De Lima
Jorge M Schmidberg
Ernesto A Duronto
Orlando C Caruso
Leonardo P Novaretto
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Guillermo D Caime
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Oscar R Codutti
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Julio A Vallejos
Rodolfo A Ahuad Guerrero
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Cristian A Patocchi
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Maria E Giuliano
Ricardo D Dran
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Miguel H Bustamante Labarta
Sebastian Nani
Eduardo DS Blumberg
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Alberto Liberman
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Mario A Berli
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Silvia S Saavedra
Gerardo Zapata
Osvaldo Costamagna
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John Horowitz
James F Rogers
David Colquhoun
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Philip Roberts-Thomson
Owen Raffel
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Constantine Aroney
Steven GM Coverdale
Paul J Garrahy
Gregory Starmer
Mark Sader
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Ronald Dick
Robert Zweiker
Uta Hoppe
Kurt Huber
Rudolf Berger
Franz Weidinger
Dirk Faes
Kurt Hermans
Bruno Pirenne
Attilio Leone
Etienne Hoffer
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
Azra Durak-Nalbantic
Dusko Vulic
Adis Muslibegovic
Boris Goronja
Gilmar Reis
Luciano Sousa
Jose C Nicolau
Flavio E Giorgeto
Ricardo P Silva
Lilia Nigro Maia
Rafael Rech
Paulo RF Rossi
Maria Jose AG Cerqueira
Norberto Duda
Renato Kalil
Adrian Kormann
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Pedro Pimentel Filho
Ana Priscila Soggia
Mayler ON de Santos
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Luiz C Bodanese
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Paulo E Leaes
Roberto V Botelho
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Dalton B Precoma
Jose C Moura Jorge
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Jose A Silveira
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Jose A Marin Neto
Gilson S Feitosa
Luiz Eduardo F Ritt
Juliana A de Souza
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Weimar KSB Souza
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Leandro Machado
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Fedya P Nikolov
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Maria L Tzekova
Haralambi O Benov
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Ronald Bourgeois
Anne Morisset
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Bruce Sussex
Simon Kouz
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Tycho Vuurmans
Christopher Lai
Frank Nigro
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Ram Vijayaraghavan
John Ducas
Serge Lepage
Shamir Mehta
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David Cleveland
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Cristian Pincetti
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Arnoldo Aguirre
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Xiaodong Li
Daoquan Peng
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Shaowen Liu
Yihua Yu
Baiming Qu
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Xingsheng Zhao
Zuyi Yuan
Ying Guo
Xiping Xu
Xubo Shi
Junbo Ge
Guosheng Fu
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Xiangjun Yang
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Ajit Bhagwat
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Jabir Abdullkutty
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Majdi Halabi
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Offer Amir
Yoseph Rozenman
Shmuel Fuchs
Osamah Hussein
Dov Gavish
Zvi Vered
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Mazen Elias
Naveh Tov
Michael Lishner
Nizar Elias
Giancarlo Piovaccari
Annamaria De Pellegrin
Gabriele Guardigli
Giovanni Licciardello
Carla Auguadro
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Salvatore Novo
Pompilio Faggiano
Nicoletta B De Cesare
Sergio Berti
Claudio Cavallini
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Piermarco Piatti
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Alessandro De Leo
Pasquale Perrone Filardi
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Vittorio Ricca
Kazuoki Dai
Haruo Kamiya
Kenji Ando
Yoshihiro Takeda
Yoshihiro Morino
Yoshiki Hata
Kazuo Kimura
Koichi Kishi
Ichiro Michishita
Hiroki Uehara
Toshinori Higashikata
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Keiji Hirooka
Satoru Sakagami
Shuichi Taguchi
Akihiro Koike
Hiroyuki Fujinaga
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Hun Sik Park
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Seungwoon Rha
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Luis Gerardo Gonzalez Salas
Enrique Lopez Rosas
Belinda Gonzalez Diaz
Eduardo Salcido Vazquez
Alfredo Nacoud Ackar
Guillermo Antonio Llamas Esperon
Carlos Rodolfo Martinez Sanchez
Maria Guerrero De Leon
Rodrigo Suarez Otero
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Russell Anscombe
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Tadeusz Tomala
Ottar Nygard
Jon Arne Sparby
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Pawel Staneta
Elzbieta Dulak
Krzysztof Saminsk
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Wanda Sudnik
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Marcin Skorski
Roman Lysek
Beata Miklaszewicz
Jacek Kubica
Jan Andrzej Lipko
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Arkadiusz Stasiewski
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Vajira Senaratne
Gnanamoorthy Mayurathan
Thilak Sirisena
Ajantha Rajapaksha
Jagath I Herath
Naomali Amarasena
Stefan Berglund
Gundars Rasmanis
Nils Witt
Georgios Mourtzinis
Peter Nicol
Ole Hansen
Stefano Romeo
Steen Agergaard Jensen
Ingemar Torstensson
Ulf Ahremark
Torbjorn Sundelin
Tiziano Moccetti
Francois Mach
Ronald Binder
Wei-Chuan Tsai
Kwo-Chang Ueng
Wen-Ter Lai
Ming-En Liu
Juey-Jen Hwang
Wei-Hsian Yin
I-Chang Hsieh
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Jen-Yuan Kuo
Tsuei-Yuan Huang
Chih-Yuan Fang
Pinij Kaewsuwanna
Wasant Soonfuang
Woravut Jintapakorn
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Nattawut Wongpraparut
Krisada Sastravaha
Nakarin Sansanayudh
Wirash Kehasukcharoen
Dilok Piyayotai
Paiboon Chotnoparatpat
Ahmet Camsari
Hakan Kultursay
Bulent Mutlu
Murat Ersanli
Mustafa Demirtas
Cevat Kirma
Ertan Ural
Lale Koldas
Oleksandr Karpenko
Alexander Prokhorov
Ihor Vakaluyk
Halyna Myshanych
Dmytro Reshotko
Valeriy Batushkin
Leonid Rudenko
Ihor Kovalskyi
Mykola Kushnir
Vira Tseluyko
Yuriy Mostovoy
Mykola Stanislavchuk
Yulian Kyiak
Yuriy Karpenko
Yaroslav Malynovsky
Andriy Klantsa
Oles Kutniy
Ekaterina Amosova
Viktor Tashchuk
Oleh Leshchuk
Mykola Rishko
Mykola Kopytsya
Andriy Yagensky
Mykola Vatutin
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Olga M Barna
Olexiy Ushakov
Georgiy Dzyak
Borys Goloborodko
Anatolii Rudenko
Volodymyr Zheleznyy
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David Sharman
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Alan Wiseman
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Carlos Ince
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Michael Rosenberg
William Rogers
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Eric Carlson
Michael D'Urso
Fadi El-Ahdab
William Nelson
Barry Harris
Steven Cohen
Luther Carter
Kenneth Sabatino
Tariq Haddad
Amir Malik
Sunder Rao
Angel Mulkay
Ion Jovin
Kim Klancke
Vinay Malhotra
Sai K Devarapalli
Michael Koren
Harish Chandna
George Dodds
Matthew Janik
Joseph Moran
Andrew Sumner
John Kobayashi
William Davis
Shahram Yazdani
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Maitreya Thakkar
Amarnath Vedere
Wayne Leimbach
James Rider
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Denise Janosik
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Friederike Keating
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Winfried Waider
Theodore Takata
Mazen Abu-Fadel
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Rahul Aggarwal
Mark Izzo
Anil Kumar
Brack Hattler
Chad Link
Anna Bortnick
George Kinzfogl
Arnold Ghitis
John Larry
Edward Teufel
Peter Kuhlman
Brent Mclaurin
Wenwu Zhang
Stephen Thew
Jalal Abbas
Matthew White
Nandkishore Ranadive
Christian Gring
David Henderson
Timothy Schuchard
Naim Farhat
Geoffrey Kline
Sharan Mahal
Jack Whitaker
Shawn Speirs
Rolf Andersen
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George Ponce
Zubair Jafar
Joseph Mcgarvey
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Thomas Blok
William Sheldon
Masoud M Azizad
Carsten Schmalfuss
Mark Picone
William Herzog
Jason Lindsey
Rosemary Nowins
Norman Lepor
Mahfouz El Shahawy
Howard Weintraub
Anand Irimpen
Wade May
Thomas Galski
Alan Chu
Freny Mody
Zachary Hodes
Gregory Rose
James Fairlamb
Charles Lambert
Ajit Raisinghani
Antonio Abbate
Marilyn King
Charles Carey
Jaime Gerber
Liwa Younis
Hyeun Tom Park
Mladen Vidovich
Thomas Knutson
Dennis Friedman
Fred Chaleff
Arthur Loussararian
Phillip Rozeman
Carey Kimmelstiel
Kevin Silver
Malcolm Foster
Glen Tonnessen
Mohamadali Amlani
Andreas Wali
Christopher Malozzi
Keattiyoat Wattanakit
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Dinesh Singal
Naseem Jaffrani
Sridhar Banuru
Daniel Fisher
Mark Xenakis
Neal Perlmutter
Ravi Bhagwat
James Strader
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Ajay Labroo
Kwan Lee
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Martin Berk
Peter Rossi
Parag Joshi
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Greg Kumkumian
Steven Lupovitch
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Stephen Welka
David Hoffman
Stuart Fischer
Eugene Soroka
Donald Eagerton
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Michael Ray
Michael Farrar
Stewart Pollock
William J French
Steve Diamantis
Lawrence Gimple
Mark Neustel
Steven Schwartz
Edward Pereira
Douglas Spriggs
Janet Strain
Anthony Vo
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Kapildeo Lotun
F Martin Lester
Ahed Nahhas
Theodore Pope
Paul Nager
Rakesh Vohra
Riyaz Bashir
Hinan Ahmed
Michael Berlowitz
Robert Fishberg
Robert Barrucco
Eric Yang
Michael Radin
Daniel Sporn
Steven Eisenberg
Joel Landzberg
Martin Mcgough
Samir Turk
Michael Schwartz
P Sandy Sundram
Diwakar Jain
Mark Zainea
Carlos Bayron
Ronald Karlsberg
Henry Lui
William Keen
Donald Westerhausen
Sandeep Khurana
Himanshu Agarwal
Jessica Birchem
William Penny
Mark Chang
Sherrill Murphy
Branislav Schifferdecker
John M Gilbert
Gopal Chalavarya
Charles Eaton
John F Schmedtje
Stuart Christenson
Douglas Denham
Alexander Macdonell
Paul Gibson
Aref Rahman
Tammam Al Joundi
Gary Conrad
Purushotham Kotha
Michael Love
Gregory Giesler
Howard Rubenstein
Laura Akright
Justine Krawczyk
Terry Wells
James Welker
Robert Foster
Richard Gilmore
Jay Anderson
Douglas Jacoby
Bill Harris
Geraldine Gardner
Ramprasad Dandillaya
Kishor Vora
John Kostis
John Hunter
David Laxson
Eric Ball
Alan Camp
Renato Lopes
Flavia Egydio
Anelise Kawakami
Janaina Oliveira
Julianna Wozniak
Alexander Matthews
Caroline Ratky
Janine Valiris
Lisa Berdan
Anita Hepditch
Kirby Quintero
Tyrus Rorick
Melissa Westbrook
Andrea Pascual
Carla Rovito
Madeleine Bezault
Elodie Drouet
Tabassome Simon
Caroline Alsweiler
Anne Luyten
Phil Aylward
Julie Butters
Liddy Griffith
Michelle Shaw
Lena Grunberg
Shahidul Islam
Nathalie Bougon
Douglas Faustino
Sylvie Fontecave
Judith Murphy
Melanie Verrier
Veronique Agnetti
Dorthe Andersen
Emmy Badreddine
Mhamed Bekkouche
Cecile Bouancheau
Imane Brigui
Maddy Brocklehurst
Joseph Cianciarulo
Dawn Devaul
Szilvia Domokos
Cecile Gache
Caroline Gobillot
Severine Guillou
Jan Healy
Megan Heath
Gayatri Jaiwal
Carine Javierre
Julien Labeirie
Myriam Monier
Ulises Morales
Asmaa Mrabti
Bicky Mthombeni
Betim Okan
Lucile Smith
Jennifer Sheller
Sebastien Sopena
Valerie Pellan
Fadela Benbernou
Nafissa Bengrait
Maud Lamoureux
Katarina Kralova
Michel Scemama
Raphael Bejuit
Anthony Coulange
Christelle Berthou
Jerome Repincay
Christelle Lorenzato
Alexis Etienne
Valerie Gouet
Virginie Loizeau
Mickael Normand
Anne Ourliac
Christelle Rondel
Antony Adamo
Pascale Beltran
Pauline Barraud
Helene Dubois-Gache
Benjamin Halle
Lamia Metwally
Maxime Mourgues
Marc Sotty
Marion Vincendet
Raluca Cotruta
Chengyue Zhu
Dominique Fournie-Lloret
Christine Morrello
Aurelie Perthuis
Patrick Picault
Isabelle Zobouyan
Publisher: LIPPINCOTT WILLIAMS & WILKINS
Identifiers: 991005956260802656
Academic Unit: Cardiology
Language: English
Resource Type: Journal article

Effect of Alirocumab on Mortality After Acute Coronary Syndromes An Analysis of the ODYSSEY OUTCOMES Randomized Clinical Trial

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