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N Engl J Med. 2017 Sep 21;377(12):1119-1131. doi: 10.1056/NEJMoa1707914. Epub 2017 Aug 27.

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease.

Collaborators (2094)

Krum H, Varigos J, Siostrzonek P, Sinnaeve P, Gotcheva N, Yong H, Urina-Triana M, Milicic D, Vettus R, Manolis AJ, Wyss F, Sigurdsson A, Fucili A, Veze I, Petrauskiene B, Salvador L, Klemsdal TO, Medina F, Budaj A, Otasevic P, Lainscak M, Seung KB, Commerford P, Donath M, Hwang JJ, Kultursay H, Bilazarian S, East C, Forgosh L, Harris B, Ligueros M, Bohula E, Charmarthi B, Cheng S, Chou S, Danik J, McMahon G, Maron B, Ning M, Olenchock B, Pande R, Perlstein T, Pradhan A, Rost N, Singhal A, Taqueti V, Wei N, Burris H, Cioffi A, Dalseg AM, Ghosh N, Gralow J, Mayer T, Rugo H, Fowler V, Limaye AP, Cosgrove S, Levine D, Lopes R, Scott J, Hilkert R, Tamesby G, Mickel C, Manning B, Woelcke J, Tan M, Manfreda S, Ponce T, Kam J, Saini R, Banker K, Salko T, Nandy P, Tawfik R, O’Neil G, Manne S, Jirvankar P, Lal S, Nema D, Jose J, Collins R, Bailey K, Blumenthal R, Colhoun H, Gersh B, Abreu M, Actis MV, Aiub J, Aiub F, Albisu J, Alvarisqueta A, Avalos V, Barreto M, Berli MA, Blumberg C, Bocanera M, Botta C, Bowen L, Budassi N, Buhlman S, Westberg JC, Carabajal T, Caruso G, Casala J, Cendali G, Coloma G, Berra FC, Cuneo C, Degennaro N, Dellasa M, Diaz M, Dos Santos P, Espinosa V, Facello A, Facello M, Farias E, Fernandez AA, Ferrari V, Pacora FF, Flores GS, Franco M, Gabito A, Viola HG, Garcia F, Garcia Duran R, Garcia Pinna J, Glenny J, Godoy Sanchez M, Grosse A, Guzman P, Hasbani E, Hominal M, Ibañez J, Jure H, Jure D, Vico ML, Liniado G, Luciardi H, Luquez H, Maehara G, Maffei L, Majul C, Mallagray M, Marinaro S, Martinez J, Massaccesi R, De Los Milagros Had M, Azize GM, Montana O, Montenegro E, Morell Y, Muntaner J, Navarrete S, Olmedo M, Paganini M, Paz S, Perez Manghi F, Piskorz D, Polato C, Recoaro R, Romano A, Salinger M, Sanchez A, Saravia MA, Sarjanovich R, Scaro G, Schiavi LB, Soler J, Tinnirello V, Tomassi A, Valle M, Vallejo MA, Venturini C, Marcela Wenetz LM, Yossen M, Zaidman C, Zalazar L, Zangroniz P, Amerena J, Brady L, Colquhoun D, Eccleston D, Ferreira-Jardim A, French J, Jayasinghe R, Mcintosh C, Ord M, Plotz M, Purnell P, Roberts-Thomson P, Schultz C, Shanahan T, Tan R, Taverner P, Turner F, Vibert J, Vorster M, William M, Youssef G, Bergler-Klein J, Brath H, Brodmann M, Fliesser-Goerzer E, Haider K, Heeren G, Hiden C, Mandic L, Paulweber B, Ploechl A, Prenner A, Steringer-Mascherbauer R, Strohner-Kaestenbauer H, Barbato E, Bouvy C, Briké C, Charlier F, Cools F, De Knijf K, De Wolf L, Delforge M, Deweerdt N, Gits F, Goffinet C, Hermans K, Hollanders G, Mestdagh I, Pirenne B, Servaes V, Simons N, Tahon S, Theunissen E, Van Genechten G, Vervoort G, Vissers C, Vranckx P, Vrolix M, Abib E Jr, Abrantes J, Araujo Fonseca M, Barbosa E, Barroso W, Barroso A, Bodanese L, Botelho R, Costa Amorim R, Da Costa F, Da Silva A, Da Silva O Jr, Da Silva D Jr, Ferreira Dos Santos T, Dos Santos F, Dos Santos A, Duda N, Feitosa G, Felario Junior GA, Ferraz R, Filho P, Fonseca A, Wanderley FF, Freitas E, Fucci F, Marengo Garcia De Carvalho L, Hernandez M, Hettwer Magedanz E, Julião K, Kormann A, Lameira A, Lima F, Lino E, Maia L, Manenti E, Marchi AL, Fischer SM, Michalaros Y, Moraes J Jr, Moreira L, Pagnan M, Pesce F, Pinheiro L, Rassi S, Reis G, Reis H, Resende I, Roel A, Ruschel K, Saporito W, Saraiva JF, Seroqui M, Silva R, Unterkircher B, Vicente C, Vieira N, Xavier JP, Zucchetti C, Angelova I, Dimitrov G, Genova D, Gospodinov K, Goudev A, Grigorova V, Hristova K, Makedonska JJ, Katova T, Kostov K, Lazov P, Manov E, Manukov I, Manukov D, Milanova M, Kabakchieva VM, Petrov D, Petrusheva T, Pramatarova I, Raev D, Runev N, Sirakova-Taseva A, Tisheva-Gospodinova S, Todorova A, Tzekova M, Yakovova S, Yanev T, Abulencia K, Arora S, Baker A, Bata IR, Beaudry M, Belle Isle J, Bilodeau N, Boivin MC, Bolduc H, Bourgeois S, Brons S, Cantor W, Chaussé I, Chhabra A, Chouinard G, Cleveland T, Dattani D, Deslongchamps F, Diodati J, Drouin K, Duchesne L, Fontaine S, d'Amours DG, Gervais B, Gosselin G, Graham J, Grover A, Gupta A, Haldane H, Hartleib M, Hickey L, Huynh T, Johnston J, Julien VE, Lachance P, Lake J, Lamontagne C, Lauzon C, Lepage S, Maheux K, Manyari D, Martin E, McPherson C, Mehta S, Michaud N, Kouz SM, Murphy G, OKeefe D, Otis R, Ouimet F, Pandey S, Peck C, Perkins L, Richert L, Robbins K, Robinson S, Cabau JR, Ross B, Roy C, Roy M, Roy A, Rupka D, Affaki GS, Saunders K, Savard D, Soucy D, St Amour E, Thiessen S, Vertes G, Vezina M, Vincelli G, Weisnagel SJ, Zadra R, Chen J, Chen Y, Dong X, Feng Y, Feng Z, Fu G, Han B, Hao Y, He Y, He Z, Hong T, Jia Z, Jiang T, Jiang J, Jiang X, Ke Y, Li Y, Li Y, Li Z, Li W, Li X, Li Y, Liu P, Liu Y, Liu B, Liu S, Liu L, Lu Z, Lv Y, Ma C, Ma G, Peng L, Qing L, Ren L, Sang X, Song M, Sun Z, Wang J, Wang Y, Wei J, Wu W, Wu J, Xu H, Yan J, Yang P, Yang K, Yao Z, Yaoqing H, Yuan Z, Zhai Z, Zhang J, Zhang Y, Zhao R, Zhou H, Accini Mendoza JL, Aparicio CV, Castillo T, Chaverra I, Conrado Y, Coronel J, Cotes C, Cuentas I, Cuervo A, Dussan MA, Echeverria L, Hernandez E, Ibarra J, Isaza D, Jimenez D, Lopez P, Manzur F, Mejia I, Mendoza Y, Molina DI, Patino JM, Rodriguez D, Rodriguez LM, Rodriguez SM, Sanchez Vallejo G, Luz Serrano H, Sotomayor A, Urina M, Vesga B, Yupanqui H, Akrap B, Busic N, Ciglenecki N, Cmrecnjak J, Fucak E, Gabor M, Jeric M, Jutrisa N, Kordic K, Planinc I, Popovic Z, Radeljic V, Sesto I, Sutalo K, Tusek S, Belohlavek J, Budkova J, Busak L, Capova L, Cech V, Cermak O, Coufalova Z, Cyprian R, Dedek V, Dedkova S, Ferkl R, Hanak P, Hanustiakova A, Homza M, Horackova K, Houra M, Iveta H, Kaiserova L, Kala P, Karel I, Kellnerova I, Koleckar P, Kreckova M, Krupicka J, Lorenc Z, Machova V, Malik J, Masarikova L, Matyasek I, Mikus M, Mikusova T, Ondrasik J, Otava M, Palubova L, Pavlickova L, Peterka M, Petrova I, Pokorna B, Povolny P, Radvan M, Reznakova S, Rickova Z, Roszkowska P, Rotreklova M, Samkova D, Skalicka H, Slechticka A, Sternthal P, Telekes P, Tesak M, Vesely P, Vesely J, Vins P, Vitovec M, Vodnansky P, Zidova M, Keba E, Laane E, Pool T, Randvee L, Ratnik E, Reimand M, Reinmets S, Rivis L, Siemann M, Stern M, Toom M, Vahula V, Apel T, Axthelm C, Ayasse D, Ayasse M, Baar M, Baeumer A, Bagi ES, Becker B, Binder A, Blankenberg S, Braun P, Johansen BB, Contzen C, Delfonso F, Denecke C, Dengler T, Donaubauer T, Eichinger G, Englmann E, Erhard M, Faghih M, Foerster A, Frankenstein L, Fuchs R, Furch G, Gaeb-Strasas B, Germann H, Giese C, Goette A, Gravenhorst-Muenter U, Haege R, Haenel T, Hagemann D, Hagenow A, Hanefeld M, Heider J, Heisters J, Hennig D, Hielscher S, Himpel-Boenninghoff A, Holscher A, Hornig M, Jeserich M, Kaczmarek N, Kanitz S, Kara YD, Khariouzov A, Kiefer R, Kiroglu K, Klamm M, Klein C, Korth-Wiemann B, Krapivsky A, Kuenzler J, Kuntzsch A, Landers B, Lappo M, Laube S, Leggewie S, Lehmann D, Lepp H, Lierse T, Lindner C, Luecke-Uzar M, Luedemann J, Marschke T, Maruzzo S, Mauersberger K, Maus O, Meinrich M, Meissner A, Moehring B, Muehlhaus J, Mueller S, Muenter KC, Muenzel T, Naumann R, Nebel J, Neumann J, Nuding S, Overhoff U, Papke B, Pencz I, Peter Y, Peukert AM, Radde I, Rau T, Regner S, Reichenbach D, Reimer D, Rinke A, Roettges R, Romanski A, Rummel R, Samer H, Sanuri M, Sarnighausen HE, Schäfer B, Scheibner T, Schermaul KH, Schindler A, Schindler A, Schlundt C, Schmidt E, Schmidt K, Schnabel A, Schoen N, Schorn K, Schroeder T, Schulenburg D, Schulz M, Schulze U, Schulze J, Schumacher M, Schwerin G, Schwerin M, Stadelmeier S, Stahl HD, Stahl A, Stockhausen J, Stockhausen G, Stoessel J, Stolze K, Stratmann M, Szymanowski N, Teschner AB, Teske A, Uecker C, Veit S, Voeller H, Walter I, Walter J, Walther I, Weber HG, Weimer J, Wichterich K, Wiebusch A, Willmerdinger M, Willner C, Winkelmann B, Winkler J, Wistuba T, Woehrle J, Wohnlich T, Wolf S, Woyczak D, Wrage P, Zirlik A, Anadiotis A, Chachalis G, Dermitzakis A, Kafarakis P, Kaldara E, Kolokathis F, Kostakou P, Lekakis J, Manolis A, Mantas I, Megalou A, Milkas A, Nanas J, Olympios CD, Patsilinakos S, Perperis A, Poulimenos L, Saloustros I, Tsioufis K, Tsorbatzoglou K, Vardas P, Zarifis I, Aguilar M, Arango JL, Borrayo NA, Corona V, Guerrero A, Guzman I, Haase F, De Krumbach L, Montenegro P, Munoz R, Munoz N, Paniagua A, Solares A, Vogel M, Anita S, Blazsek Z, Decsi K, Fulop T, Hangyal T, Hegedus V, Kalina A, Karakai H, Katona A, Kiss RG, Kovacs A, Laszlo Z, Lupkovics G, Medvegy M, Merkely B, Mihaly N, Nagy AC, Dékány JN, Nikoletta P, Noori E, Penzes J, Poor F, Sarszegi Z, Simay A, Simon J, Szakal I, Szatmarine V, Szocs A, Zilahi Z, Karsai XZ, Andersen K, Sigurdadottir E, Skuladottir F, Abdullakutty J, Abhaichand R, Abhyankar A, Agarwal DK, Aggarwal RK, Ahire N, Awasthi AK, Babu R, Bai A, Bali HK, Banker D, Bhadade S, Bisne V, Bohra P, Raghu C, Chauhan D, Chauhan H, Chavada J, Chaware G, Chella S, Chintala P, Dash D, Desai D, Devasia T, Dhanak R, Dobariya H, Dudhatra N, Duhan S, Fulwani M, Ghondale N, Ghosh S, Gohel P, Govindaraj D, Goyal B, Goyal S, Gundala AK, Gupta A, Gupta M, Hardas S, Iby M, Jagtap P, Jain A, Joshi U, Karpuram M, Kaur H, Khan A, Khan R, Kodem DR, Koeitti P, Kulkarni L, Kullal P, Kumar KS, Kumbla M, Latheef K, Lohkare M, Santosh MJ, Makhe B, Mandati M, Mehta A, Minocha G, Mittal A, Modi R, Mohan K, Oomman A, Pai R, Pai V, Palaniswami N, Pansheriya A, Parekh N, Patel J, Patel R, Patole T, Praveen M, Radhakrishnan V, Rajan B A, Rajasekhar D, Rao M, Rao MB, Rao NM, Rathnavel S, Rathore A, Rathore SRS, Rawat S, Reddy NC, Sarma R, Sathe S, Shah J, Shaikh P, Sharma K, Sharma S, Sharma T, Shetty P, Sidhu G, Singh V, Sohi GS, Srinath VS, Raju SS, Taran A, Thakkar B, Velusamy K, Vijan V, Vora V, Vuriya AK, Agosta GF, Antonicelli R, Ardissino D, Argiolas G, Baldin MG, Benedetti G, Berti S, Bevilacqua MT, Bolognesi MG, Dessalvi CC, Calabrese A, Campanale EG, Candusso R, Caso P, Cosmi F, Crea F, Crocamo A, De Caterina R, De Rosa S, Destro M, Di Biase M, Dognini GP, Eleuteri E, Fedele F, Ferrario M, Gabrielli D, Gamba C, Ganau A, Gravellone M, Iannopollo G, Indolfi C, Infusino F, Invitti C, Landolfi A, Lembo G, Liberato NL, Mannucci E, Marino P, Mariottoni B, Marziali A, Mercuro G, Monti L, Mos L, Mureddu V, Musumeci MB, Novo S, Panzarino C, Parente A, Perotti M, Filardi PP, Petrillo C, Piatti P, Priori S, Racca V, Ragghianti B, Renda G, Righini V, Sarcone M, Senni M, Soro E, Tamburrini P, Vallone L, Villani GQ, Volpe M, Ajioka M, Akai Y, Ashino K, Baden M, Doi M, Eki Y, Endo T, Fukuike C, Hagiwara Y, Hasegawa K, Higuchi Y, Higuchi T, Hioki M, Hirayama A, Hiroma J, Hosokawa S, Ichisawa M, Iijima T, Inada T, Inagaki M, Ito K, Kaigawa K, Kajihara S, Kamiya H, Kamiya J, Kaneno Y, Katahira K, Kataoka M, Kawai M, Kawasaki T, Kojima E, Komura Y, Kuramochi T, Kuruma T, Kyo E, Mani H, Miyamoto T, Morii I, Morinaga Y, Morisawa T, Nagai Y, Naka T, Nakamura Y, Nakamura S, Nakayoshi K, Nishibe A, Ogawa M, Okada Y, Okawa M, Sakamoto Y, Sakurada M, Sasaki S, Seki S, Shimomura H, Shinozaki T, Sugimoto N, Suzuki A, Taguchi S, Takahashi J, Takase S, Tanabe K, Tanaka A, Tani S, Tomioka J, Tsuboi H, Tsuji M, Tsujita K, Tsujiyama S, Umesu A, Yamada T, Yamaguchi E, Yamamoto H, Yamamoto T, Yamane M, Yanase T, Yasuoka S, Yasutake M, Yokoyama M, Yoshida M, Yoshimoto E, Yunoki C, Balode A, Dormidontova G, Flaksa I, Nagele-Luse I, Rancane G, Sime I, Bartuseviciene S, Cepinskiene L, Dobilas V, Grigaraviciene I, Marcinkeviciene J, Mazutavicius R, Miliuniene R, Motiejuniene R, Norkiene S, Norkute-Macijauske U, Rudys A, Slapikas R, Stonkute K, Strazdiene D, Tijuneliene E, Urbonas G, Vanagiene S, Viezelis M, Aguilar M, Arenas Leon JL, Bayram E, Carrillo J, Davalos C, De Los Rios M, Delgadillo T, Hernández N, Leon S, Mendoza N, Muñoz W, Ramos G, Anneveldt A, Bakker H, Brouwer M, Bunschoten P, De Boer P, De Jong C, De Vos A, Den Hartog F, Doesborg L, Dommerholt R, Drost I, Ellenbroek D, Engelen W, Folkeringa RJ, Hamer BJB, Herrman JP, Hoogslag PAM, Jansen M, Jerzewski A, Joosten C, Kalkman C, Kietselaer B, Kok M, Kooiman E, Kose V, Lardinois R, Lenderink T, Lok DJA, Lousberg A, Meijlis P, Mulder R, Singerling M, Smeele F, Stroes E, Swart HP, Ten Holt W, Van Der Wal M, Van Der Zwaan C, Van Kempen WW, Van Maarseveen M, Van Stein I, Viergever EP, Visseren FLJ, Voors C, Nugteren SKZ, Ata B, Berulfsen A, Rønnevik TD, Dickstein K, Furuseth B, Grundtvig M, Hansen H, Hofsoey K, Høivik HO, Bøen RH, Hurtig U, Pettersen KI, Johansen E, Kleve R, Kolleroy C, Moen S, Nilsen V, Norin V, Otterstad JE, Risberg K, Rønnevik P, Sirnes PA, Skjelvan G, Strand S, Szacinski G, Vegsundvåg J, Alcalde JM, Gomez Sanchez J, Rodriguez J, Rodriguez A, Zena N, Baszak J, Cymerman K, Czerski T, Fratczak M, Jaguszewska G, Kawka-Urbanek T, Koba M, Kopaczewski J, Kopczyńska M, Laniec M, Lysek R, Sciborski R, Szpajer M, Torun A, Wujkowski M, Zielinski M, Ahn Y, Baek C, Bang SA, Chang K, Choi AJ, Han S, Hong T, Hyun K, Kim M, Kim KS, Kim B, Lee SH, Lee J, Lee HN, Lee JH, Lee KR, Moon K, Park B, Park C, Tahk S, Yim KH, Yim S, Tase T, Andor M, Aron G, Badea C, Casoinic F, Clocotan M, Coman S, Emil B, Imre BS, Istratoaie O, Liviu C, Maximov D, Militaru C, Minescu B, Istvan KP, Parepa I, Petrescu L, Podoleanu C, Pop CF, Popa V, Popescu E, Radoi M, Sarbu I, Socoteanu E, Socoteanu G, Sorodoc L, Spiridon M, Stanciulescu G, Stefanescu M, Tanaseanu C, Tudoran M, Zdrenghea D, Agafina A, Akatova E, Avdonina N, Balukova E, Barbarash OL, Bartosh L, Boyarkin M, Bulashova O, Burova N, Churina S, Demidova M, Dorogova I, Dovgalevskiy Y, Dovgolis S, Dudarev M, Fitilev S, Gapon L, Gazizianova V, Gordeev I, Ivanov I, Izmozherova N, Kazanskay E, Khirmanov V, Khromtsova O, Konradi A, Kosmacheva E, Kozlova S, Kulibaba E, Kuzin A, Libov I, Lipchenko A, Lozhkina N, Malchikova S, Morozov E, Myslyaeva L, Onuchina E, Palatkina T, Panov A, Parmon E, Petelina T, Repin A, Reznik I, Sazonova E, Sergienko T, Shaposhnik I, Shapovalova Y, Shustov S, Shvarts Y, Skopets I, Skuratova M, Smolenskaya O, Solovev O, Trofimov V, Vasiliev M, Vezikova N, Vozzhaev A, Yakushin S, Zadionchenko V, Apostolovic S, Adjic NC, Ilic I, Ilic S, Nikolic L, Pupic L, Stokuca-Korac N, Antalik L, Bugan V, Csala L, Dokupilova A, Dzupina A, Forgon T, Fulop P, Gonsorcik J, Gyorgyova E, Holoubek D, Horvat P, Kamensky G, Kolikova V, Krupciakova B, Lenner E, Lennerova J, Lukac J, Majercak I, Mancikova I, Micko K, Nociar J, Pales J, Palka J Jr, Poliacik P, Ruffini L, Sabo L, Skubova K, Slanina M, Smik R, Srdos V, Stitova M, Stofkova D, Strbova J, Such S, Toth P, Urgeova L, Vinanska D, Zareczky P, Flezar M, Kovacic D, Marcun R, Zagozen P, Bolsmann C, Commerford P, Conradie C, Dawood SY, Decsi KL, Ebrahim I, Henley L, Horak A, Kapp I, Komati S, Lock E, Maboyi S, Makotoko E, Manga P, Page A, Ramdas S, Ranjith N, Roos J, Talliard C, Ajax K, Al-Khalili F, Assarsson E, Bergholtz T, Blom KB, Boman K, Boström PÅ, Curiac D, Jensen ED, Dahlen G, Davidsson K, Duckert A, Hansson A, Härstedt N, Henriksson A, Olsson GH, Johansson K, Jonsson JE, Knutsson A, Lindholm CJ, Liu B, Lönnberg I, Lundqvist M, Mellberg L, Moodh J, Mooe T, Olofsson M, Risenfors M, Rönndahl M, Sundelin R, Suorra I, Torgersruud M, Torstensson I, Chang KC, Chen CP, Chen ZC, Chen MH, Cheng SM, Cheng JJ, Fang CY, Ho CJ, Hsieh IC, Huang PH, Huang A, Hwang JJ, Kuo JY, Lai WT, Lee SC, Li YH, Lin T, Liu HM, Tsai MC, Tsao HM, Tzong L, Ueng KC, Wang YL, Wang HC, Wang CP, Yang CC, Abaci F, Birdane A, Yilmaz MB, Asim Oktay AO, Kan G, Koldas N, Ozcan IT, Sahin M, Sahin T, Saka B, Tekten T, Ucar N, Uresin S, Yigit Z, Arif I, Bakhai A, Baksi A, Blagdon M, Brickman T, Brown N, Burton M, Burton J, Chaggar S, Chung A, Collier D, Covell W, Crawford G, Davies N, Davies M, Dayer M, Doughty A, Duff J, Dwenger E, Fisher J, Fitzpatrick L, Garner K, Glover J, Haughton G, Ilsley M, Ivan P, Voyzey EJ, Keenan S, Kelt T, Knight J, Kondagunta V, Lang C, Lee K, Lim L, Macdonald J, Mathew A, Mckenzie A, Mckibbin A, Michalska A, Pagett K, Pogson A, Price R, Price D, Procter K, Pye M, Redfearn H, Rewbury J, Ryding A, Sattar N, Sharp A, Shaw P, Simpson H, Smith W, Squire I, Storey R, Teenan M, Thomas H, Townend J, Trevelyan J, Wakeling J, Walukiewicz P, Wilkinson S, Zaman A, Acevedo L, Benton J, Abbate A, Aboufakher R, Acampora M, Acampora D, Aceto L, Acevedo B, Acheatel R, Adams M, Adams A, Ahmad I, Ahmed SH, Aish B, Akyea-Djamson A, Al Joundi T, Alcide P, Alfieri A, Alfonso T, Alfrey A, Allen J, Alllison DC, Almaliky T, Amos A, Angiolillo D, Antolick A, Ara M, Aragorn L, Arevalo S, Armas E, Arthur A, Asafu-Adjaye N, Ashcom T, Ashford M, Aslam A, Ather N, Atieh M, Aull L, Ayala M, Azizad M, Backer T, Baehl S, Bailey S, Bair S, Baker C, Ballmajo M, Pieretti HB, Baquero A, Barnett S, Baron S, Bartkowiak A, Bashir K, Beall K, Beauregard LA, Sarah S, Beckett L, Belejchak P, Bendelow T, Bender D, Benjamin S, Berdoff R, Berger V, Bergeron P, Berk M, Bernstein M, Binns Y, Bitzer V, Blahey M, Bloch S, Bluemel J, Boffetti P, Boley K, Bonner J, Boudreaux R, Boulanger K, Bradley A, Bramlet D, Bredlau C, Briggs S, Brousalis L, Brown S, Brown C, Buchannan 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Abstract

BACKGROUND:

Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved.

METHODS:

We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death.

RESULTS:

At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31).

CONCLUSIONS:

Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846 .).

PMID:
28845751
DOI:
10.1056/NEJMoa1707914
[Indexed for MEDLINE]

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