Safety of the PCSK9 inhibitor alirocumab: insights from 47 296 patient-years of observation

Author:

Goodman Shaun G12ORCID,Steg Philippe Gabriel3,Szarek Michael45ORCID,Bhatt Deepak L6ORCID,Bittner Vera A7,Diaz Rafael8ORCID,Harrington Robert A9,Jukema J Wouter1011ORCID,White Harvey D12,Zeiher Andreas M13,Manvelian Garen14,Pordy Robert14ORCID,Poulouin Yann15,Stipek Wanda14,Garon Genevieve16,Schwartz Gregory G17, ,Schwartz Gregory G,Steg Ph Gabriel,Bhatt Deepak L,Bittner Vera A,Diaz Rafael,Goodman Shaun G,Harrington Robert A,Jukema J Wouter,Szarek Michael,White Harvey D,Zeiher Andreas M,Tricoci Pierluigi,Roe Matthew T,Mahaffey Kenneth W,Edelberg Jay M,Hanotin Corinne,Lecorps Guillaume,Moryusef Angèle,Pordy Robert,Sasiela William J,Tamby Jean-François,Diaz Rafael,Aylward Philip E,Drexel Heinz,Sinnaeve Peter,Dilic Mirza,Lopes Renato D,Gotcheva Nina N,Goodman Shaun G,Prieto Juan-Carlos,Yong Huo,López-Jaramillo Patricio,Pećin Ivan,Reiner Zeljko,Ostadal Petr,Poulsen Steen Hvitfeldt,Viigimaa Margus,Nieminen Markku S,Danchin Nicolas,Chumburidze Vakhtang,Marx Nikolaus,Liberopoulos Evangelos,Valdovinos Pablo Carlos Montenegro,Tse Hung-Fat,Kiss Robert Gabor,Xavier Denis,Zahger Doron,Valgimigli Marco,Kimura Takeshi,Kim Hyo Soo,Kim Sang-Hyun,Erglis Andrejs,Laucevicius Aleksandras,Kedev Sasko,Yusoff Khalid,López Gabriel Arturo Ramos,Alings Marco,White Harvey D,Halvorsen Sigrun,Flores Roger M Correa,Sy Rody G,Budaj Andrzej,Morais Joao,Dorobantu Maria,Karpov Yuri,Ristic Arsen D,Chua Terrance,Murin Jan,Fras Zlatko,Dalby Anthony J,Tuñón José,de Silva H Asita,Hagström Emil,Landmesser Ulf,Chiang Chern-En,Sritara Piyamitr,Guneri Sema,Parkhomenko Alexander,Ray Kausik K,Moriarty Patrick M,Chaitman Bernard,Kelsey Sheryl F,Olsson Anders G,Rouleau Jean-Lucien,Simoons Maarten L,Alexander Karen,Meloni Chiara,Rosenson Robert,Sijbrands Eric J G,Tricoci Pierluigi,Alexander John H,Armaganijan Luciana,Bagai Akshay,Bahit Maria Cecilia,Brennan J Matthew,Clifton Shaun,DeVore Adam D,Deloatch Shalonda,Dickey Sheila,Dombrowski Keith,Ducrocq Grégory,Eapen Zubin,Endsley Patricia,Eppinger Arleen,Harrison Robert W,Hess Connie Ng,Hlatky Mark A,Jordan Joseph Dedrick,Knowles Joshua W,Kolls Bradley J,Kong David F,Leonardi Sergio,Lillis Linda,Lopes Renato D,Maron David J,Mahaffey Kenneth W,Marcus Jill,Mathews Robin,Mehta Rajendra H,Mentz Robert J,Patel Chetan B,Pereira Sabrina Bernardez,Perkins Lynn,Povsic Thomas J,Puymirat Etienne,Roe Matthew T,Jones William Schuyler,Shah Bimal R,Sherwood Matthew W,Stringfellow Kenya,Sujjavanich Darin,Toma Mustafa,Trotter Charlene,van Diepen Sean F P,Wilson Matthew D,Yan Andrew Tze-Kay,Schiavi Lilia B,Garrido Marcelo,Alvarisqueta Andrés F,Sassone Sonia A,Bordonava Anselmo P,De Lima Alberto E Alves,Schmidberg Jorge M,Duronto Ernesto A,Caruso Orlando C,Novaretto Leonardo P,Hominal Miguel Angel,Montaña Oscar R,Caccavo Alberto,Vilamajo Oscar A Gomez,Lorenzatti Alberto J,Cartasegna Luis R,Paterlini Gustavo A,Mackinnon Ignacio J,Caime Guillermo D,Amuchastegui Marcos,Salomone Oscar,Codutti Oscar R,Jure Horacio O,Bono Julio O E,Hrabar Adrian D,Vallejos Julio A,Guerrero Rodolfo A Ahuad,Novoa Federico,Patocchi Cristian A,Zaidman Cesar J,Giuliano Maria E,Dran Ricardo D,Vico Marisa L,Carnero Gabriela S,Guzman Pablo N,Allende Juan C Medrano,Brasca Daniela F Garcia,Labarta Miguel H Bustamante,Nani Sebastian,Blumberg Eduardo D S,Colombo Hugo R,Liberman Alberto,Fuentealba Victorino,Luciardi Hector L,Waisman Gabriel D,Berli Mario A,Garcia Duran Ruben O,Cestari Horacio G,Luquez Hugo A,Giordano Jorge A,Saavedra Silvia S,Zapata Gerardo,Costamagna Osvaldo,Llois Susana,Waites Jonathon H,Collins Nicholas,Soward Allan,Aylward Philip E,Hii Chris L S,Aylward Philip E,Shaw James,Arstall Margaret A,Horowitz John,Ninio Daniel,Rogers James F,Colquhoun David,Flores Romulo E Oqueli,Roberts-Thomson Philip,Raffel Owen,Lehman Sam J,Aroney Constantine,Coverdale Steven G M,Garrahy Paul J,Starmer Gregory,Sader Mark,Carroll Patrick A,Dick Ronald,Zweiker Robert,Hoppe Uta,Drexel Heinz,Huber Kurt,Berger Rudolf,Delle-Karth Georg,Frey Bernhard,Faes Dirk,Hermans Kurt,Pirenne Bruno,Leone Attilio,Hoffer Etienne,Sinnaeve Peter,Vrolix Mathias C M,De Wolf Luc,Wollaert Bart,Castadot Marc,Dujardin Karl,Beauloye Christophe,Vervoort Geert,Striekwold Harry,Convens Carl,Roosen John,Barbato Emanuele,Claeys Marc,Cools Frank,Terzic Ibrahim,Barakovic Fahir,Midzic Zlatko,Pojskic Belma,Fazlibegovic Emir,Dilic Mirza,Durak-Nalbantic Azra,Kulić Mehmed,Vulic Dusko,Muslibegovic Adis,Goronja Boris,Reis Gilmar,Sousa Luciano,Nicolau Jose C,Giorgeto Flavio E,Silva Ricardo P,Maia Lilia Nigro,Rech Rafael,Rossi Paulo R F,Cerqueira Maria José A G,Duda Norberto,Kalil Renato,Kormann Adrian,Abrantes José Antonio M,Filho Pedro Pimentel,Soggia Ana Priscila,de Santos Mayler O N,Neuenschwander Fernando,Bodanese Luiz C,Michalaros Yorghos L,Eliaschewitz Freddy G,Vidotti Maria H,Leaes Paulo E,Botelho Roberto V,Kaiser Sergio,Manenti Euler Roberto F Fernandes,Precoma Dalton B,Jorge Jose C Moura,Silva Pedro,Silveira Jose A,Saporito Wladmir,Neto Jose A Marin,Feitosa Gilson S,Ritt Luiz Eduardo F,de Souza Juliana A,Costa Fernando,Souza Weimar K S B,Reis Helder J L,Lopes Renato D,Machado Leandro,Ayoub José Carlos Aidar,Todorov Georgi V,Nikolov Fedya P,Velcheva Elena S,Tzekova Maria L,Benov Haralambi O,Petranov Stanislav L,Tumbev Haralin S,Shehova-Yankova Nina S,Markov Dimitar T,Raev Dimitar H,Mollov Mihail N,Kichukov Kostadin N,Ilieva-Pandeva Katya A,Gotcheva Nina N,Ivanova Raya,Gospodinov Maryana,Mincheva Valentina M,Lazov Petar V,Dimov Bojidar I,Senaratne Manohara,Stone James,Kornder Jan,Dion Danielle,Savard Daniel,Pesant Yves,Pandey Amritanshu,Robinson Simon,Gosselin Gilbert,Vizel Saul,Hoag Gordon,Bourgeois Ronald,Morisset Anne,Sabbah Eric,Sussex Bruce,Kouz Simon,MacDonald Paul,Diaz Ariel,Michaud Nicolas,Fell David,Vuurmans Tycho,Lai Christopher,Nigro Frank,Davies Richard,Nogareda Gustavo,Vijayaraghavan Ram,Ducas John,Lepage Serge,Mehta Shamir,Cha James,Dupuis Robert,Fong Peter,Lutchmedial Sohrab,Rodes-Cabau Josep,Fadlallah Hussein,Cleveland David,Huynh Thao,Bata Iqbal,Hameed Adnan,Pincetti Cristian,Potthoff Sergio,Prieto Juan C,Acevedo Monica,Aguirre Arnoldo,Vejar Margarita,Yañez Mario,Araneda Guillermo,Fernandez Mauricio,Perez Luis,Varleta Paola,Florenzano Fernando,Huidobro Laura,Raffo Carlos A,Olivares Claudia,Nahuelpan Leonardo,Montecinos Humberto,Chen Jiyan,Dong Yugang,Huang Weijian,Wang Jianzhong,Huang Shi'An,Yao Zhuhua,Li Xiang,Cui Lan,Lin Wenhua,Sun Yuemin,Wang Jingfeng,Li Jianping,Zhang Xuelian,Zhu Hong,Chen Dandan,Huang Lan,Dong Shaohong,Su Guohai,Xu Biao,Su Xi,Cheng Xiaoshu,Lin Jinxiu,Zong Wenxia,Li Huanming,Feng Yi,Xu Dingli,Yang Xinchun,Ke Yuannan,Lin Xuefeng,Zhang Zheng,Zheng Zeqi,Luo Zhurong,Chen Yundai,Ding Chunhua,Zhong Yi,Zheng Yang,Li Xiaodong,Peng Daoquan,Zhao Shuiping,Li Ying,Liu Xuebo,Wei Meng,Liu Shaowen,Yu Yihua,Qu Baiming,Jiang Weihong,Zhou Yujie,Zhao Xingsheng,Yuan Zuyi,Guo Ying,Xu Xiping,Shi Xubo,Ge Junbo,Fu Guosheng,Bai Feng,Fang Weiyi,Shou Xiling,Yang Xiangjun,Wang Jian'An,Xiang Meixiang,Sun Yingxian,Lu Qinghua,Zhang Ruiyan,Zhu Jianhua,Xu Yizhou,Fan Zhongcai,Li Tianchang,Wu Chun,Jaramillo Nicolas,Vallejo Gregorio Sanchez,Luna Botia Diana C,Lopez Rodrigo Botero,Molina De Salazar Dora I,Cadena Bonfanti Alberto J,Aroca Carlos Cotes,Higuera Juan Diego,Blanquicett Marco,Barrera Silva Sandra I,Lozada Henry J Garcia,Coronel Arroyo Julian A,Accini Mendoza Jose L,Ruiz Ricardo L Fernandez,Quintero Ossa Alvaro M,Manzur Jatin Fernando G,Herazo Aristides Sotomayor,Parada Jeffrey Castellanos,Arambula Rafael Suarez,Triana Miguel A Urina,Fernandez Trujillo Angela M,Strozzi Maja,Car Siniša,Jerić Melita,Benčić Martina Lovrić,Pintarić Hrvoje,Prvulović Đeiti,Šikić Jozica,Peršić Viktor,Mileta Dean,Štambuk Kresimir,Babić Zdravko,Tomulic Vjekoslav,Lukenda Josip,Mejic-Krstulovic Stanka,Starcevic Boris,Spinar Jindrich,Horak David,Velicka Zdenek,Stasek Josef,Alan David,Machova Vilma,Linhart Ales,Novotny Vojtech,Kaucak Vladimir,Rokyta Richard,Naplava Robert,Coufal Zdenek,Adamkova Vera,Podpera Ivo,Zizka Jiri,Motovska Zuzana,Marusincova Ivana,Svab Premysl,Ostadal Petr,Heinc Petr,Kuchar Jiri,Povolny Petr,Matuska Jiri,Poulsen Steen H,Raungaard Bent,Clemmensen Peter,Bang Lia E,May Ole,Bøttcher Morten,Hove Jens D,Frost Lars,Gislason Gunnar,Larsen John,Johansen Peter Betton,Hald Flemming,Johansen Peter,Jeppesen Jørgen,Nielsen Tonny,Kristensen Kjeld S,Walichiewicz Piotr Maria,Lomholdt Jens D,Klausen Ib C,Nielsen Peter Kaiser,Davidsen Flemming,Videbaek Lars,Viigimaa Margus,Soots Mai,Vahula Veiko,Hedman Anu,Soopõld Üllar,Märtsin Kaja,Jurgenson Tiina,Kristjan Arved,Nieminen Markku S,Huikuri Heikki,Coste Pierre,Ferrari Emile,Danchin Nicolas,Morel Olivier,Montalescot Gilles,Machecourt Jacques,Barone-Rochette Gilles,Mansourati Jacques,Cottin Yves,Steg Ph Gabriel,Leclercq Florence,Belhassane Abdelkader,Delarche Nicolas,Boccara Franck,Paganelli Franck,Clerc Jérôme,Schiele Francois,Aboyans Victor,Probst Vincent,Berland Jacques,Lefèvre Thierry,Citron Bernard,Chumburidze Vakhtang,Khintibidze Irakli,Shaburishvili Tamaz,Pagava Zurab,Ghlonti Ramaz,Lominadze Zaza,Khabeishvili George,Hemetsberger Rayyan,Edward Kemala,Rauch-Kröhnert Ursula,Stratmann Matthias,Appel Karl-Friedrich,Schmidt Ekkehard,Omran Heyder,Stellbrink Christoph,Dorsel Thomas,Lianopoulos Emmanouil,Vöhringer Hans Friedrich,Marx Roger,Zirlik Andreas,Schellenberg Detlev,Heitzer Thomas,Laufs Ulrich,Werner Christian,Marx Nikolaus,Gielen Stephan,Nuding Sebastian,Winkelmann Bernhard,Behrens Steffen,Sydow Karsten,Karakas Mahir,Simonis Gregor,Muenzel Thomas,Werner Nikos,Leggewie Stefan,Böcker Dirk,Braun-Dullaeus Rüdiger,Toursarkissian Nicole,Jeserich Michael,Weißbrodt Matthias,Schaeufele Tim,Weil Joachim,Völler Heinz,Waltenberger Johannes,Natour Mohammed,Schmitt Susanne,Müller-Wieland Dirk,Steiner Stephan,Heidenreich Lothar,Offers Elmar,Gremmler Uwe,Killat Holger,Rieker Werner,Patsilinakos Sotiris,Kartalis Athanasios,Manolis Athanassios,Sionis Dimitrios,Chachalis Geargios,Liberopoulos Evangelos,Skoumas Ioannis,Athyros Vasilios,Vardas Panagiotis,Parthenakis Frangkiskos,Alexopoulos Dimitrios,Hahalis Georgios,Lekakis John,Hatzitolios Apostolos,Ovando Sergio R Fausto,Valdovinos Pablo Carlos Montenegro,Arango Benecke Juan L,Rodriguez De Leon Edgar R,Yan Bryan P Y,Siu David C W,Turi Tibor,Merkely Bela,Kiss Robert Gabor,Ungi Imre,Lupkovics Geza,Nagy Lajos,Katona András,Édes István,Müller Gábor,Horvath Iván,Kapin Tibor,Szigeti Zsolt,Faluközy József,Kumbla Mukund,Sandhu Manjinder,Annam Sharath,Proddutur Naveen Reddy,Regella Reddy,Premchand Rajendra K,Mahajan Ajaykumar,Pawar Sudhir,Abhyanakar Atul D,Kerkar Prafulla,Govinda Ravishankar A,Oomman Abraham,Sinha Dhurjati,Patil Sachin N,Kahali Dhiman,Sawhney Jitendra,Joshi Abhijeet B,Chaudhary Sanjeev,Harkut Pankaj,Guha Santanu,Porwal Sanjay,Jujjuru Srimannarayana,Pothineni Ramesh B,Monteiro Minguel R,Khan Aziz,Iyengar Shamanna S,Grewal Jasprakash Singh,Chopda Manoj,Fulwani Mahesh C,Patange Dr Aparna,Sachin Patil,Chopra Vijay K,Goyal Naresh K,Shinde Rituparna,Manakshe Gajendra V,Patki Nitin,Sethi Sumeet,Munusamy Vengatesh,Thanvi Sunil Karnaand Sunil,Adhyapak Srilakshmi,Patil Chandrakant,Pandurangi Ulhas,Mathur Rishabh,Gupta Jugal,Kalashetti Suhas,Bhagwat Ajit,Raghuraman Bagirath,Yerra Shiv Kumar,Bhansali Prasant,Borse Rohidas,Rahul Patil,Das Srihari,Kumar Vinay,Abdullakutty Jabir,Saathe Shireesh,Palimkar Priya,Abdullkutty Jabir,Sathe Shireesh,Atar Shaul,Shechter Michael,Mosseri Morris,Arbel Yaron,Ehud Chorin,Ofer Havakuk,Lotan Chaim,Rosenschein Uri,Katz Amos,Henkin Yaakov,Francis Adi,Klutstein Marc,Nikolsky Eugenia,Zukermann Robert,Turgeman Yoav,Halabi Majdi,Marmor Alon,Kornowski Ran,Jonas Michael,Amir Offer,Hasin Yonathan,Rozenman Yoseph,Fuchs Shmuel,Zvi Vered,Hussein Osamah,Gavish Dov,Vered Zvi,Caraco Yoseph,Elias Mazen,Tov Naveh,Wolfovitz Efrat,Lishner Michael,Elias Nizar,Piovaccari Giancarlo,De Pellegrin Annamaria,Garbelotto Raffaella,Guardigli Gabriele,Marco Valgimigli,Licciardello Giovanni,Auguadro Carla,Scalise Filippo,Cuccia Claudio,Salvioni Alessandro,Musumeci Giuseppe,Senni Michelle,Calabrò Paolo,Novo Salvatore,Faggiano Pompilio,Metra Marco,De Cesare Nicoletta B,Berti Sergio,Cavallini Claudio,Puccioni Enrico,Galvani Marcello,Tespili Maurizio,Piatti Piermarco,Palvarini Michela,De Luca Giuseppe,Violini Roberto,De Leo Alessandro,Olivari Zoran,Filardi Pasquale Perrone,Ferratini Maurizio,Racca Vittorio,Dai Kazuoki,Shimatani Yuji,Kamiya Haruo,Ando Kenji,Takeda Yoshihiro,Morino Yoshihiro,Hata Yoshiki,Kimura Kazuo,Kishi Koichi,Michishita Ichiro,Uehara Hiroki,Higashikata Toshinori,Hirayama Atsushi,Hirooka Keiji,Doi Yasuji,Sakagami Satoru,Taguchi Shuichi,Koike Akihiro,Fujinaga Hiroyuki,Koba Shinji,Kozuma Ken,Kawasaki Tomohiro,Ono Yujiro,Shimizu Masatoshi,Katsuda Yousuke,Wada Atsuyuki,Shinke Toshiro,Kimura Takeshi,Ako Junya,Fujii Kenshi,Takahashi Toshiyuki,Sakamoto Tomohiro,Nakao Koichi,Furukawa Yutaka,Sugino Hiroshi,Tamura Ritsu,Mano Toshiaki,Uematsu Masaaki,Utsu Noriaki,Ito Kashima,Haraguchi Takuya,Sato Katsuhiko,Ueda Yasunori,Nishibe Akira,Fujimoto Kazuteru,Masutani Motomaru,Nishibe Akira,Fujimoto Kazuteru,Yoon Jung Han,Kim Sang-Hyun,Kim Hack-Lyoung,Park Hun Sik,Chae In-Ho,Kim Moo Hyun,Jeong Myung Ho,Rha Seungwoon,Kim Chongjin,Kim Hyo-Soo,Kim Hae Young,Hong Taekjong,Tahk Seung-Jea,Kim Youngkwon,Busmane Arija,Pontaga Natalija,Strelnieks Aldis,Mintale Iveta,Sime Iveta,Petrulioniene Zaneta,Kavaliauskiene Roma,Jurgaitiene Ruta,Sakalyte Gintare,Slapikas Rimvydas,Norkiene Sigute,Misonis Nerijus,Kibarskis Aleksandras,Kubilius Raimondas,Bojovski Stojko,Kedev Sasko,Lozance Nensi,Kjovkaroski Aleksandar,Doncovska Snezana,Ong Tiong Kiam,Kasim Sazzli,Maskon Oteh,Kandasamy Balachandran,Yusoff Khalid,Liew Houng B,Mohamed Wan Mohd Izani Wan,Castillo Armando García,López Gabriel Arturo Ramos,Calvillo Jorge Carrillo,Campos Pedro Fajardo,Fragoso Juan Carlos Núñez,Llamas Edmundo Alfredo Bayram,Gamba Marco Antonio Alcocer,Madrigal Jaime Carranza,Salas Luis Gerardo González,Rosas Enrique López,Díaz Belinda González,Vázquez Eduardo Salcido,Ackar Alfredo Nacoud,Esperón Guillermo Antonio Llamas,Sánchez Carlos Rodolfo Martínez,De Leon María Guerrero,Otero Rodrigo Suarez,Salmón Guillermo Fanghänel,Ríos Jesús Antonio Pérez,Ruíz José Angel Garza,Alings Marco,Breedveld Robert W,Feenema-Aardema Margriet,Borger-Van Der Burg Alida,Hoogslag Pieter A M,Suryapranata Harry,Oomen Antonius,Van Haelst Paulus,Feenema-Aradema Margriet,Wiersma Jacobijne J,Basart Dirk,Van Der Wal Ruud M A,Zwart Peter,Monraats Pascalle,Van Kesteren Henricus,Karalis Ioannis,Jukema Johan,Verdel Gerardus J E,Brueren Bart R G,Troquay Roland P T h,Viergever Eric P,Al-Windy Nadea Y Y,Bartels Gerard L,Cornel Jan H,Hermans Walter R M,Herrman Johannes P R,Bos Robert J,Groutars Reginald G E J,Van Der Zwaan Coenraad C,Kaplan Refik,Lionarons Raymond,Ronner Eelko,Groenemeijer Bjorn E,Bronzwaer Patrick N A,Liem Anho A H,Rensing Bernard J W M,Bokern Marcel J J A,Nijmeijer Remco,Hersbach Ferry M R J,Willems Frank F,Gosselink Antonius T M,Rasoul Saman,Elliott John,Wilkins Gerard,Fisher Raewyn,Scott Douglas,Hart Hamish,Stewart Ralph,Harding Scott,Ternouth Ian,Fisher Nicholas,Wilson Samuel,Aitken Denise,Anscombe Russell,Davidson Laura,Tomala Tadeusz,Nygård Ottar,Sparby Jon Arne,Andersen Kjell,Gullestad Lars,Jortveit Jarle,Munk Peter S,Singsaas Erlend gyllensten,Halvorsen Sigrun,Hurtig Ulf,Correa Flores Roger M,Calderon Ticona Jorge R,Velasquez Julio R Durand,Miguel Sandra A Negron,Perez Enrique S Sanabria,Carrion Chambilla Jesus M,Chavez Ayala Carlos A,Leon Reynaldo P Castillo,Vargas Gonzales Rolando J,Hernandez Zuniga Jose D,Cosavalente Luis A Camacho,Bravo Mannucci Jorge E,Landeo Javier Heredia,Llerena Navarro Nassip C,Concha Yudy M Roldan,Rodriguez Chavez Víctor E,Anchante Hernandez Henry A,Zea Nunez Carlos A,Ramos Walter Mogrovejo,Ferrolino Arthur,Sy Rosa Allyn G,Tirador Louie,Sy Rody G,Matiga Generoso,Coching Raul Martin,Bernan Alisa,Rogelio Gregorio,Morales Dante D,Tan Edgar,Sulit Dennis Jose,Wlodarczak Adrian,Jaworska Krystyna,Skonieczny Grzegorz,Pawlowicz Lidia,Wojewoda Pawel,Busz-Papiez Benita,Bednarski Janusz,Goch Aleksander,Staneta Pawel,Dulak Elzbieta,Budaj Andrzej,Saminski Krzysztof,Krasowski Wlodzimierz,Sudnik Wanda,Zurakowski Aleksander,Skorski Marcin,Lysek Roman,Miklaszewicz Beata,Kubica Jacek,Lipko Jan Andrzej,Kostarska-Srokosz Edyta,Piepiorka Marek,Drzewiecka Anna,Sciborski Ryszard,Stasiewski Arkadiusz,Blicharski Tomasz,Bystryk Leszek,Szpajer Michal,Korol Marek,Czerski Tomasz,Mirek-Bryniarska Ewa,Gniot Jacek,Lubinski Andrzej,Gorny Jerzy,Franek Edward,Raczak Grzegorz,Szwed Hanna,Monteiro Pedro,Bastos Jose Mesquita,Pereira Helder H,Martins Dinis,Morais Joao,Seixo Filipe,Mendonça Carlos,Botelho Ana,Caetano Francisca,Minescu Bogdan,Istratoaie Octavian,Tesloianu Dan N,Dorobantu Maria,Cristian Gabriel,Dumitrescu Silviu,Podoleanu Cristian G C,Constantinescu Mircea C A,Bengus Cristina M,Militaru Constantin,Rosu Doina,Parepa Irinel R,Matei Adrian V,Alexandru Tom M,Malis Mihaela,Coman Ioan,Stanescu-Cioranu Rodica,Dimulescu Doina,Shvarts Yury,Orlikova Olga,Kobalava Zhanna,Barbarash Olga L,Markov Valentin,Lyamina Nadezhda,Gordienko Alexander,Zrazhevsky Konstantin,Vishnevsky Alexander Y,Gurevich Victor,Stryuk Raisa,Lomakin Nikita V,Bokarev Igor,Khlevchuk Tatiana,Shalaev Sergey,Khaisheva Larisa,Chizhov Petr,Viktorova Inna,Osokina Natalya,Shchekotov Vladimir,Akatova Evgenia,Chumakova Galina,Libov Igor,Voevoda Mikhail I,Tretyakova Tatyana V,Baranov Evgeny,Shustov Sergey,Yakushin Sergey,Gordeev Ivan,Khasanov Niiaz,Reshetko Olga,Sotnikova Tatiana,Molchanova Olga,Nikolaev Konstantin,Gapon Liudmila,Baranova Elena,Shogenov Zaur,Kosmachova Elena,Karpov Yuriy,Karpov Yuri,Povzun Anton,Egorova Liudmila,Tyrenko Vadim V,Ivanov Igor G,Ilya Masterov,Kanorsky Sergey,Simic Dragan,Ivanovic Nikola,Davidovic Goran,Tasic Nebojsa,Asanin Milika R,Stojic Stevo,Apostolovic Svetlana R,Ilic Stevan,Tosic Biljana Putnikovic,Stankovic Aleksandar,Arandjelovic Aleksandra,Radovanovic Slavica,Todic Branislava,Ristic Arsen D,Balinovac Jovan,Dincic Dragan V,Seferovic Petar,Karadzic Ana,Dodic Slobodan,Dimkovic Sinisa,Jakimov Tamara,Chua Terrance,Poh Kian-Keong,Ong Hean Yee,Tang I-Shing Justin,Micko Karol,Nociar Jan,Pella Daniel,Fulop Peter,Hranai Marian,Palka Juraj,Mazur Juraj,Majercák Ivan,Dzupina Andrej,Fazekas František,Gonsorcik Jozef,Bugan Viliam,Murin Jan,Selecky Juraj,Kamensky Gabriel,Strbova Jaroslava,Smik Rudolf,Dukat Andrej,Olexa Peter,Žuran Ivan,Poklukar Janez,Šuligoj Nataša Černič,Cevc Matija,Fras Zlatko,Cyster Henry P,Ranjith Naresh,Corbett Clive,Bayat Junaid,Makotoko Ellen Makoali,du Toit Theron Hendrik,Kapp Ilse E,de V Basson Matthys M,Lottering Hanlie,Van Aswegen Dina,Van Zyl Louis J,Sebastian Peter J,Pillay Thayabran,Saaiman Jan A,Commerford Patrick J,Cassimjee Soraya,Riaz Garda,Ebrahim Iftikhar O,Sarvan Mahomed,Mynhardt Joseph H,Dalby Anthony J,Reuter Helmuth,Moodley Rajendran,Vida Manuel,Cequier Fillat Angel R,Peris Vicente Bodí,Jimenez Francisco Fuentes,Marín Francisco,Fernández Jose M Cruz,Urbano Rafael Jesus Hidalgo,Gil-Extremera Blas,Toledo Pablo,Diz Fernando Worner,Garcia-Dorado David,Iñiguez Andres,Fernández José Tuñón,Gonzalez-Juanatey Jose R,Portales Javier Fernandez,Murillo Fernando Civeira,Pericas Laia Matas,Zamorano Jose Luis,Martin Manuel De Mora,Cortada Jordi Bruguera,Alonso Martin Joaquin J,Antolin Jose Maria Serrano,De Berrazueta Fernández José R,de Prada José Antonio Vázquez,Fernández Jose Francisco Díaz,Lledó José Alberto García,Sales Juan Cosín,Rodriguez Javier Botas,Tragant Gabriel Gusi,Benedicto Amparo,Gonzalez-Juanatey Carlos,Potau Mercedes Camprubí,Perez Ignacio Plaza,De La Tassa César Morís,Rincon Pablo Loma-Osorio,Recena Javier Balaguer,Escudier Juan M,Payeras Antonio Coca,Orcajo Norberto Alonso,Valdivielso Pedro,Constantine Godwin,Haniffa Ruvaiz,Tissera Nirmali,Amarasekera Stanley,Ponnamperuma Chandrike,Fernando Nimali,Fernando Kaputella,Jayawardena Jayanthimala,Wijeyasingam 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Oleksandr,Prokhorov Alexander,Vakaluyk Ihor,Myshanych Halyna,Reshotko Dmytro,Batushkin Valeriy,Rudenko Leonid,Kovalskyi Ihor,Kushnir Mykola,Tseluyko Vira,Mostovoy Yuriy,Stanislavchuk Mykola,Kyiak Yulian,Karpenko Yuriy,Malynovsky Yaroslav,Klantsa Andriy,Kutniy Oles,Amosova Ekaterina,Tashchuk Viktor,Leshchuk Oleh,Parkhomenko Alexander,Rishko Mykola,Kopytsya Mykola,Yagensky Andriy,Vatutin Mykola,Bagriy Andriy,Barna Olga M,Ushakov Olexiy,Dzyak Georgiy,Goloborodko Borys,Rudenko Anatolii,Zheleznyy Volodymyr,Trevelyan Jasper,Zaman Azfar,Lee Kaeng,Moriarty Andrew,Aggarwal Rajesh K,Clifford Piers,Wong Yuk-Ki,Iqbal Syed M R,Subkovas Eduardas,Braganza Denise,Sarkar David,Storey Robert,Griffiths Huw,Mcclure Sam,Muthusamy Rangasamy,Smith Simon,Kurian John,Levy Terry,Barr Craig,Kadr Honer,Gerber Robert,Simaitis Audrius,Soran Handrean,Mathur Anthony,Brodison Adrian,Ayaz Mohammad,Cheema Muhammad,Oliver Richard,Thackray Simon,Mudawi Telal,Rahman Gohar,Sultan Ayyaz,Reynolds Timothy,Sharman 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E,Butters Julie,Griffith Liddy,Shaw Michelle,Hagström Emil,Grunberg Lena,Szarek Michael,Islam Shahidul,Brégeault Marie-France,Bougon Nathalie,Faustino Douglas,Fontecave Sylvie,Murphy Judith,Tamby Jean-Francois,Verrier Melanie,Agnetti Veronique,Andersen Dorthe,Badreddine Emmy,Bekkouche Mhamed,Bouancheau Cecile,Brigui Imane,Brocklehurst Maddy,Cianciarulo Joseph,Devaul Dawn,Domokos Szilvia,Gache Cecile,Gobillot Caroline,Guillou Severine,Healy Jan,Heath Megan,Jaiwal Gayatri,Javierre Carine,Labeirie Julien,Monier Myriam,Morales Ulises,Mrabti Asmaa,Mthombeni Bicky,Okan Betim,Smith Lucile,Sheller Jennifer,Sopena Sebastien,Pellan Valerie,Benbernou Fadela,Bengrait Nafissa,Lamoureux Maud,Kralova Katarina,Scemama Michel,Bejuit Raphael,Coulange Anthony,Berthou Christelle,Repincay Jérôme,Lorenzato Christelle,Etienne Alexis,Gouet Valerie,Lecorps Guillaume,Loizeau Virginie,Normand Mickael,Ourliac Anne,Rondel Christelle,Adamo Antony,Beltran Pascale,Barraud Pauline,Dubois-Gache Helene,Halle Benjamin,Metwally Lamia,Mourgues Maxime,Sotty Marc,Vincendet Marion,Cotruta Raluca,Chengyue Zhu,Fournie-Lloret Dominique,Morrello Christine,Perthuis Aurelie,Picault Patrick,Zobouyan Isabelle,Colhoun Helen M,Dempsey Michael A,McClanahan Mark A

Affiliation:

1. Canadian VIGOUR Centre, University of Alberta , Edmonton, Alberta , Canada

2. St. Michael's Hospital, University of Toronto , Toronto, Ontario , Canada

3. Université Paris-Cité, Institut Universitaire de France, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, FACT (French Alliance for Cardiovascular Trials), and INSERM U1148 , F-75018 Paris , France

4. CPC Clinical Research and Division of Cardiology, University of Colorado School of Medicine , Aurora, 80045 CO , USA

5. State University of New York, Downstate Health Sciences University , Brooklyn, NY 11203 , USA

6. Mount Sinai Heart, Icahn School of Medicine at Mount Sinai , New York, NY 10029 , USA

7. Division of Cardiovascular Disease, University of Alabama at Birmingham , Birmingham, AL 35233 , USA

8. Estudios Cardiológicos Latinoamérica, Instituto Cardiovascular de Rosario , S2000 Rosario , Argentina

9. Cornell University , New York, NY 10065 , USA

10. Department of Cardiology, Leiden University Medical Center , 2333 ZA Leiden , The Netherlands

11. Netherlands Heart Institute , 3511 EP Utrecht , The Netherlands

12. Green Lane Cardiovascular Research Unit, Te Whatu Ora—Health New Zealand, Te Toka Tumai, and University of Auckland , Auckland 1030 , New Zealand

13. Department of Medicine III, Goethe University , 60596 Frankfurt am Main , Germany

14. Regeneron Pharmaceuticals Inc. , Tarrytown, NY 10591 , USA

15. IT&M Stats , Neuilly-sur-Seine 92200 , France

16. Sanofi , Toronto, ON M2R 3T4 , Canada

17. University of Colorado School of Medicine , Aurora 80045, CO , USA

Abstract

Abstract The ODYSSEY OUTCOMES trial, comprising over 47 000 patient-years of placebo-controlled observation, demonstrated important reductions in the risk of recurrent ischaemic cardiovascular events with the monoclonal antibody to proprotein convertase subtilisin/kexin type 9 alirocumab, as well as lower all-cause death. These benefits were observed in the context of substantial and persistent lowering of low-density lipoprotein cholesterol with alirocumab compared with that achieved with placebo. The safety profile of alirocumab was indistinguishable from matching placebo except for a ∼1.7% absolute increase in local injection site reactions. Further, the safety of alirocumab compared with placebo was evident in vulnerable groups identified before randomization, such as the elderly and those with diabetes mellitus, previous ischaemic stroke, or chronic kidney disease. The frequency of adverse events and laboratory-based abnormalities was generally similar to that in placebo-treated patients. Thus, alirocumab appears to be a safe and effective lipid-modifying treatment over a duration of at least 5 years.

Funder

Sanofi

Regeneron Pharmaceuticals, Inc.

Publisher

Oxford University Press (OUP)

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