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2. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
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Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ, Novo S, 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, 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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, 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 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, 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, 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, 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, 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, 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, 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, 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0301 basic medicine ,030204 cardiovascular system & hematology ,law.invention ,0302 clinical medicine ,c-reactive protein ,Randomized controlled trial ,law ,Cardiovascular Disease ,middle aged ,double-blind method ,antibodies ,Myocardial infarction ,humans ,Stroke ,interleukin-1beta ,biology ,Antibodies, Monoclonal ,drug ,General Medicine ,Lipid ,Aged ,anti-inflammatory agents ,monoclonal ,humanized ,atherosclerosis ,cardiovascular diseases ,dose-response relationship ,female ,incidence ,infections ,lipids ,male ,myocardial infarction ,neutropenia ,secondary prevention ,stroke ,Anti-Inflammatory Agent ,aged ,Editorial ,Atherosclerosi ,Monoclonal ,Human ,medicine.drug ,medicine.medical_specialty ,Neutropenia ,Antibodies, Monoclonal, Humanized ,Infections ,Placebo ,antibodies, monoclonal ,dose-response relationship, drug ,infection ,medicine (all) ,03 medical and health sciences ,Internal medicine ,medicine ,Dose-Response Relationship, Drug ,business.industry ,Antiinflammatory Therapy, Canakinumab, for Atherosclerotic Disease ,C-reactive protein ,medicine.disease ,Surgery ,Canakinumab ,030104 developmental biology ,biology.protein ,business - 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.)
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- 2017
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3. Antiinflammatory therapy with canakinumab for atherosclerotic disease
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Ridker P.M., Everett B.M., Thuren T., MacFadyen J.G., Chang W.H., Ballantyne C., Fonseca F., Nicolau J., Koenig W., Anker S.D., Kastelein J.J.P., Cornel J.H., Pais P., Pella D., Genest J., Cifkova R., Lorenzatti A., Forster T., Kobalava Z., Vida-Simiti L., Flather M., Shimokawa H., Ogawa H., Dellborg M., Rossi P.R.F., Troquay R.P.T., Libby P., Glynn R.J., Krum H., Varigos J., Siostrzonek P., Sinnaeve P., Gotcheva N., Yong H., Urina-Triana M., Milicic D., Vettus R., Manolis A.J., Wyss F., Sigurdsson A., Fucili A., Veze I., Petrauskiene B., Salvador L., Klemsdal T.O., Medina F., Budaj A., Otasevic P., Lainscak M., Seung K.B., Commerford P., Donath M., Hwang J.J., 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 A.M., Ghosh N., Gralow J., Mayer T., Rugo H., Fowler V., Limaye A.P., 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 M.V., Aiub J., Aiub F., Albisu J., Alvarisqueta A., Avalos V., Barreto M., Berli M.A., Blumberg C., Bocanera M., Botta C., Bowen L., Budassi N., Buhlman S., Westberg J.C., Carabajal T., Caruso G., Casala J., Cendali G., Coloma G., Berra F.C., Cuneo C., Degennaro N., Dellasa M., Diaz M., Dos Santos P., Espinosa V., Facello A., Facello M., Farias E., Fernandez A.A., Ferrari V., Pacora F.F., Flores G.S., Franco M., Gabito A., Viola H.G., 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 M.L., 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 G.M., 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 M.A., Sarjanovich R., Scaro G., Schiavi L.B., Soler J., Tinnirello V., Tomassi A., Valle M., Vallejo M.A., Venturini C., Marcela Wenetz L.M., 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 F.F., 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 A.L., Fischer S.M., 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 J.F., Seroqui M., Silva R., Unterkircher B., Vicente C., Vieira N., Xavier J.P., Zucchetti C., Angelova I., Dimitrov G., Genova D., Gospodinov K., Goudev A., Grigorova V., Hristova K., Makedonska J.J., Katova T., Kostov K., Lazov P., Manov E., Manukov I., Manukov D., Milanova M., Kabakchieva V.M., 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 I.R., Beaudry M., Belle Isle J., Bilodeau N., Boivin M.C., 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 D.G., Gervais B., Gosselin G., Graham J., Grover A., Gupta A., Haldane H., Hartleib M., Hickey L., Huynh T., Johnston J., Julien V.E., Lachance P., Lake J., Lamontagne C., Lauzon C., Lepage S., Maheux K., Manyari D., Martin E., McPherson C., Mehta S., Michaud N., Kouz S.M., Murphy G., OKeefe D., Otis R., Ouimet F., Pandey S., Peck C., Perkins L., Richert L., Robbins K., Robinson S., Cabau J.R., Ross B., Roy C., Roy M., Roy A., Rupka D., Affaki G.S., Saunders K., Savard D., Soucy D., St Amour E., Thiessen S., Vertes G., Vezina M., Vincelli G., Weisnagel S.J., 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 Z., Li W., Li X., 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 C.V., Castillo T., Chaverra I., Conrado Y., Coronel J., Cotes C., Cuentas I., Cuervo A., Dussan M.A., Echeverria L., Hernandez E., Ibarra J., Isaza D., Jimenez D., Lopez P., Manzur F., Mejia I., Mendoza Y., Molina D.I., Patino J.M., Rodriguez D., Rodriguez L.M., Rodriguez S.M., 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 E.S., Becker B., Binder A., Blankenberg S., Braun P., Johansen B.B., 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 Y.D., 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 K.C., Muenzel T., 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A., Mantas I., Megalou A., Milkas A., Nanas J., Olympios C.D., Patsilinakos S., Perperis A., Poulimenos L., Saloustros I., Tsioufis K., Tsorbatzoglou K., Vardas P., Zarifis I., Aguilar M., Arango J.L., Borrayo N.A., 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 R.G., Kovacs A., Laszlo Z., Lupkovics G., Medvegy M., Merkely B., Mihaly N., Nagy A.C., Dékány J.N., Nikoletta P., Noori E., Penzes J., Poor F., Sarszegi Z., Simay A., Simon J., Szakal I., Szatmarine V., Szocs A., Zilahi Z., Karsai X.Z., Andersen K., Sigurdadottir E., Skuladottir F., Abdullakutty J., Abhaichand R., Abhyankar A., Agarwal D.K., Aggarwal R.K., Ahire N., Awasthi A.K., Babu R., Bai A., Bali H.K., 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 A.K., Gupta M., Hardas S., Iby M., Jagtap P., Jain A., Joshi U., Karpuram M., Kaur H., Khan A., Khan R., Kodem D.R., Koeitti P., Kulkarni L., Kullal P., Kumar K.S., Kumbla M., Latheef K., Lohkare M., Santosh M.J., 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 M.B., Rao N.M., Rathnavel S., Rathore A., Rathore SRS., Rawat S., Reddy N.C., Sarma R., Sathe S., Shah J., Shaikh P., Sharma K., Sharma S., Sharma T., Shetty P., Sidhu G., Singh V., Sohi G.S., Srinath V.S., Raju S.S., Taran A., Thakkar B., Velusamy K., Vijan V., Vora V., Vuriya A.K., Agosta G.F., Antonicelli R., Ardissino D., Argiolas G., Baldin M.G., Benedetti G., Berti S., Bevilacqua M.T., Bolognesi M.G., Dessalvi C.C., Calabrese A., Campanale E.G., Candusso R., Caso P., Cosmi F., Crea F., Crocamo A., De Caterina R., De Rosa S., Destro M., Di Biase M., Dognini G.P., 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 N.L., Mannucci E., Marino P., Mariottoni B., Marziali A., Mercuro G., Monti L., Mos L., Mureddu V., Musumeci M.B., Novo S., Panzarino C., Parente A., Perotti M., Filardi P.P., 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 G.Q., 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., 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 R.J., Hamer BJB., Herrman J.P., 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 H.P., Ten Holt W., Van Der Wal M., Van Der Zwaan C., Van Kempen W.W., Van Maarseveen M., Van Stein I., Viergever E.P., Visseren FLJ., Voors C., Nugteren SKZ., Ata B., Berulfsen A., Rønnevik T.D., Dickstein K., Furuseth B., Grundtvig M., Hansen H., Hofsoey K., Høivik H.O., Bøen R.H., Hurtig U., Pettersen K.I., Johansen E., Kleve R., Kolleroy C., Moen S., Nilsen V., Norin V., Otterstad J.E., Risberg K., Rønnevik P., Sirnes P.A., Skjelvan G., Strand S., Szacinski G., Vegsundvåg J., Alcalde J.M., 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 S.A., Chang K., Choi A.J., Han S., Hyun K., Kim M., Kim K.S., Kim B., Lee S.H., Lee J., Lee H.N., Lee J.H., Moon K., Park B., Park C., Tahk S., Yim K.H., Yim S., Tase T., Andor M., Aron G., Badea C., Casoinic F., Clocotan M., Coman S., Emil B., Imre B.S., Istratoaie O., Liviu C., Maximov D., Militaru C., Minescu B., Istvan K.P., Parepa I., Petrescu L., Podoleanu C., Pop C.F., 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 O.L., 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 N.C., 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., Conradie C., Dawood S.Y., Decsi K.L., 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 K.B., Boman K., Boström P.A., Curiac D., Jensen E.D., Dahlen G., Davidsson K., Duckert A., Hansson A., Härstedt N., Henriksson A., Olsson G.H., Johansson K., Jonsson J.E., Knutsson A., Lindholm C.J., Lönnberg I., Lundqvist M., Mellberg L., Moodh J., Mooe T., Olofsson M., Risenfors M., Rönndahl M., Sundelin R., Suorra I., Torgersruud M., Torstensson I., Chen C.P., Chen Z.C., Chen M.H., Cheng S.M., Cheng J.J., Fang C.Y., Ho C.J., Hsieh I.C., Huang P.H., Huang A., Kuo J.Y., Lai W.T., Lee S.C., Lin T., Liu H.M., Tsai M.C., Tsao H.M., Tzong L., Ueng K.C., Wang Y.L., Wang H.C., Wang C.P., Yang C.C., Abaci F., Birdane A., Yilmaz M.B., Asim Oktay AO., Kan G., Koldas N., Ozcan I.T., 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 E.J., 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., 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W., Caballero-Valiente B., Carr K., Halliwell T.C., Castillo J., Cei L., Cerda L., Chambers J., Chamblee T., Chattin W., Chee L., Chen Y.C., Cherlin R., Cheung D., Chiodi L., Christensen L., Christenson S., Cislowski D., Clavier-Firmin C., Colfer H., Colvin T., Cosgrove N., Covert C., Cox B., Cox R., Craig W., Crandall L., Crepps K., Cromer M., Cruz H., Cruz M., Cucher F., Damron M., Dave K., Dave B., Davis M., Davis B., Dawkins-Hughes S., Dean J., Debnam S., Defosse C., Dehning M., Dela Llana A., Dellorso M., Denham D., Desalle D., Dettmer M., Dhawan M., Diago M., Dicken T., Diederich C., Diederich M., Diehl R., Digangi D., Diller P., Dimattia M., Dodds G., Doggett J., Donahue K., Doughty L., Dragutksy B., Dreese M., Dunhurst F., Dunn D., Dutka C., Earl J., Eaton C., Eaves W., Ebeling K., Eder F., Edgerton L., Edillo C., Edwards J., Edwards T., Einhorn D., El Hafi S., Ellis M., Erickson B., Ervin W., Eskridge L., Fail P., Falcon D., Fang C., Fattal P., Fawson A., Felix L., Ferdinand K., Fien E., Fintel D., Firek C., Fitz-Patrick D., Flores E., Flores H., Floro T., Forker A., Foster M., Foucauld J., Lehman K.F., Fox B., Francoeur L., Frandsen B., Frivold G., Fruchter G., Fullerton D., Gabriel J., Gacioch G., Garas S., Garcia N., Garcia Rinaldi R., Garcia-Fragoso V., Garcia-Portela M., Gelb R., George F., Ghali J., Gilbert J., Gilley J., Glancy R., Goff R., Goldberg N., Gonzales D., Gonzales V., Gonzalez E., Gorges R., Gould R., Grabeau R., Grable M., Graham J.A., Graif J., Green E., Greener R., Greenway F., Grieshaber V., Griffin S., Gros C., Gudipati RVC., Guillinta P., Gupta V., Gutmann J., Gwyn M., El Hachem M., Hage F., Hageman T., Haidar A., Hakas J., Haldis T., Hall L., Hall C., Hall S., Halpern S., Hamud-Socoro A., Hardee L., Harrell W., Harrington A., Hartwell J., Hasan F., Hattler B., Haught H., Haynes E., Haywood A., Heaney L., Hecht J., Hernandez I., Herzog W., Hess E., Hill H., Hilton T., Hinderaker P., Hodnett P., Hoffman M., Hogan C., Holmes Z., Rees D.H., Hotchkiss D., Huang P., Humbert J., Hutchens E., Iachini K., Ibarra M., Igbokidi O., Ilahi T., Imbrognio M., Ipp E., Iteld B., Jacques G., Jafri A., Jafry B., Jardula M., Jefferson D., Jenkins R., Johnson E., Johnson J., Jones S., Kawahara M., Kelehan S., Kelly R., Kendall T., Kereiakes D., Khan M., Khan S., Kick J., Kimmel M., King T., King A., Kirkland S., Kissel S., Kitchens D., Klein P., Klugherz B., Korban E., Koren M., Korte M., Kostis J., Kotek L., Kozak M., Kreutter F., Kusnick B., Labovitz R., Lail J., Lamance J., Lamas G., Lambert J., Lambert C., Landzberg J., Langdon J., Lavoie W., Ledger G., Lee T., Lehman R., Leimbach W., Lennard M., Lepor N., Lester F., Levin P., Levinson L., Lewis D., Lillo J., Link L., Long C., Longaker R., Lorch G., Lucksinger G., Lynd S., Rhudy J.M., Madder R., Magness K., Maheshwari A., Alan A., Malek M., Maletz L., Malhotra V., Malhotra S., Mandviwala M., Mani C.K., Manuel J., Marchelletta N., Marshall L., Marsters M., Martin L., Martinez E., Mavromatis K., Maynard R., Mays M., Mays B., Mbulaiteye A., Mcalister R., Mccoy C., Mccrary D.Jr., Mccullough-O'Brien H., Mcdonald M., Mcgill J., Mcgrew F., Mckenzie C., Mclaurin B., Mclellan B.A., Mcneil D., Mcneill R., Mehrle A., Melbie K., Melliza T., Messina T., Meyer R., Michel K., Mikdadi G., Miller C., Miller R., Miller A., Miller G., Miller W., Mitchell J., Moats DJR., Mody F., Moffat J., Molk B., Molter D., Monroe T., Montero H., Montgomery R., Mookherjee D., Moran J., Moriarty P., Morrison J., Morton D., Moshayedi P., Mosley J., Moustafa M., Munshi K., Murray A., Mustafa J., Nadar V., Naidu R., Nalley J., Navy S., Neil L., Neutel J.M., Niblack P., Nicely V., Nicolai M., Nijmeh G., Nikas A., Nikyar A., Nixon S., Norman L., Noto G., Nour K., Nugent A., Ocman B., Odegard A., Olsen S., Ortiz-Carrasquillo R., Ossino N., Paez H., Palchick B., Paliwal Y., Pannell R., Parfait V., Partridge J., Patel B., Patel M., Patel S., Paysor C., Pena A., Pereira S., Perez M., Perez A., Perkins H., Perry B., Peters P., Phillippi C., Phillips A., Piacente R., Pintado M., Pish R., Pitt W., Poling T., Pomposini D., Poock J., Potts J., Poudrier R., Prior J., Pritchard C., Purighalla R., Quddusi K., Quinones J., Quinton D., Radin M., Radojcsics B., Rajput B., Rama B., Ramos M., Rauch R., Raynes K., Reber A.M., Reddy J., Reeves M., Reilly K., Renaud K., Resnick H., Reyes R., Richardson M., Riethof M., Riser J., Rodero M., Rodriguez Araya E., Roper L., Rozeman P., Ruder D., Runquist L., Sack G., Saint-Jacques H., Salfity M., Sall N., Sam K., Samal A., Sanchez D., Santiago J.Jr., Savignano C., Saylor R., Scheffel M., Schifferdecker B., Schindler E., Schneider P., Schneider R., Schnitzler R., Schrager B., Schwartz A., Scott R., Seals A., Shah A.V., Shah A., Shatsky K., Shayani S., Shealy N., Sheets L., Shelley J., Shepard P., Shetty S., Silver K., Simon M., Singh K., Singh N., Sizemore B.C., Skatrud L., Slayton C., Slimak V., Sloane G., Smallwood B., Smith P., Smith M., Smith T., Smith G., Smith B., Smith J., Soca Y., Sofley C., Sopko K., Sosa-Padilla M., Sotolongo R., Sprinkle B., Srivastava S., Starzec M., Steinhoff J., Stelly L., Stinson J., Stoddard M., Stoltz S., Stone B., Stover T., Strain J., Strugatsky S., Stys T., Suleman A., Sullivan P., Tamez W., Tandon N., Teltser M., Terry P.S., Terry K., Tessmar C., Thekkoott D., Thomas D., Thomas D.M., Thompson E., Thompson J., Thornton A., Tjaden T., Tobias C., Topper J., Tran A., Treasure C., Trenkamp P., Trevino M., Tsou L., Tuholske C., Uy W., Vahtel M., Vaid B., Valenzuela M., Vance A., Vandam J., Vanhecke T., Vanness WC III., Vargas R., Vaz S., Vazquez Tanus J., Veerina K., Vega J., Vento A., Vijay N., Voelker F., Vogt E., Vold D., Vora K., Wade R.D., Wadell C., Waksman R., Walker K., Wallace K., Warren M., Washam M., Watson B., Webel R., Wells T., West M., Whitaker J., White J., White C., White A., Wilhoit G., Wilkins M., Willingham K., Wilson S., Wilson V., Wise J., Woodall S., Woods A., Wright J., Xu Z.J., Yarows S., Young A., Younis L., Zarate J., Zebrack J., Zhang W., Zieve F., Zineldine A., Ridker P.M., Everett B.M., Thuren T., MacFadyen J.G., Chang W.H., Ballantyne C., Fonseca F., Nicolau J., Koenig W., Anker S.D., Kastelein J.J.P., Cornel J.H., Pais P., Pella D., Genest J., Cifkova R., Lorenzatti A., Forster T., Kobalava Z., Vida-Simiti L., Flather M., Shimokawa H., Ogawa H., Dellborg M., Rossi P.R.F., Troquay R.P.T., Libby P., Glynn R.J., Krum H., Varigos J., Siostrzonek P., Sinnaeve P., Gotcheva N., Yong H., Urina-Triana M., Milicic D., Vettus R., Manolis A.J., Wyss F., Sigurdsson A., Fucili A., Veze I., Petrauskiene B., Salvador L., Klemsdal T.O., Medina F., Budaj A., Otasevic P., Lainscak M., Seung K.B., Commerford P., Donath M., Hwang J.J., 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 A.M., Ghosh N., Gralow J., Mayer T., Rugo H., Fowler V., Limaye A.P., 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 M.V., Aiub J., Aiub F., Albisu J., Alvarisqueta A., Avalos V., Barreto M., Berli M.A., Blumberg C., Bocanera M., Botta C., Bowen L., Budassi N., Buhlman S., Westberg J.C., Carabajal T., Caruso G., Casala J., Cendali G., Coloma G., Berra F.C., Cuneo C., Degennaro N., Dellasa M., Diaz M., Dos Santos P., Espinosa V., Facello A., Facello M., Farias E., Fernandez A.A., Ferrari V., Pacora F.F., Flores G.S., Franco M., Gabito A., Viola H.G., Garcia F., Garcia Duran R., Garcia Pinna J., Glenny J., Godoy Sanchez M., Grosse A., Guzman P., Hasbani E., 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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 F.F., 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 A.L., Fischer S.M., 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., 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Mehta S., Michaud N., Kouz S.M., Murphy G., OKeefe D., Otis R., Ouimet F., Pandey S., Peck C., Perkins L., Richert L., Robbins K., Robinson S., Cabau J.R., Ross B., Roy C., Roy M., Roy A., Rupka D., Affaki G.S., Saunders K., Savard D., Soucy D., St Amour E., Thiessen S., Vertes G., Vezina M., Vincelli G., Weisnagel S.J., 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 Z., Li W., Li X., 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 C.V., Castillo T., Chaverra I., Conrado Y., Coronel J., Cotes C., Cuentas I., Cuervo A., Dussan M.A., Echeverria L., Hernandez E., Ibarra J., Isaza D., Jimenez D., Lopez P., Manzur F., Mejia I., Mendoza Y., Molina D.I., Patino J.M., Rodriguez D., Rodriguez L.M., Rodriguez S.M., 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 E.S., Becker B., Binder A., Blankenberg S., Braun P., Johansen B.B., 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 Y.D., 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 K.C., Muenzel T., Naumann R., Nebel J., Neumann J., Nuding S., Overhoff U., Papke B., Pencz I., Peter Y., Peukert A.M., Radde I., Rau T., Regner S., Reichenbach D., Reimer D., Rinke A., Roettges R., Romanski A., Rummel R., Samer H., Sanuri M., Sarnighausen H.E., Schäfer B., Scheibner T., Schermaul K.H., 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 H.D., Stahl A., Stockhausen J., Stockhausen G., Stoessel J., Stolze K., Stratmann M., Szymanowski N., Teschner A.B., Teske A., Uecker C., Veit S., Voeller H., Walter I., Walter J., Walther I., Weber H.G., 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 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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 A.K., Gupta M., Hardas S., Iby M., Jagtap P., Jain A., Joshi U., Karpuram M., Kaur H., Khan A., Khan R., Kodem D.R., Koeitti P., Kulkarni L., Kullal P., Kumar K.S., Kumbla M., Latheef K., Lohkare M., Santosh M.J., 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 M.B., Rao N.M., Rathnavel S., Rathore A., Rathore SRS., Rawat S., Reddy N.C., Sarma R., Sathe S., Shah J., Shaikh P., Sharma K., Sharma S., Sharma T., Shetty P., Sidhu G., Singh V., Sohi G.S., Srinath V.S., Raju S.S., Taran A., Thakkar B., Velusamy K., Vijan V., Vora V., Vuriya A.K., Agosta 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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., 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 R.J., Hamer BJB., Herrman J.P., 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 H.P., Ten Holt W., Van Der Wal M., Van Der Zwaan C., Van Kempen W.W., Van Maarseveen M., Van Stein I., Viergever E.P., Visseren FLJ., Voors C., Nugteren SKZ., Ata B., Berulfsen A., Rønnevik T.D., Dickstein K., Furuseth B., Grundtvig M., Hansen H., Hofsoey K., Høivik H.O., Bøen R.H., Hurtig U., Pettersen K.I., Johansen E., Kleve R., Kolleroy 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Willingham K., Wilson S., Wilson V., Wise J., Woodall S., Woods A., Wright J., Xu Z.J., Yarows S., Young A., Younis L., Zarate J., Zebrack J., Zhang W., Zieve F., and Zineldine A.
- 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
4. Phospho-SIM and exon8b of PML protein regulate formation of doxorubicin-induced rDNA-PML compartment.
- Author
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Hornofova T, Pokorna B, Hubackova SS, Uvizl A, Kosla J, Bartek J, Hodny Z, and Vasicova P
- Subjects
- DNA, Ribosomal genetics, Doxorubicin pharmacology, Protein Isoforms metabolism, Tumor Suppressor Proteins genetics, Tumor Suppressor Proteins metabolism, Nuclear Proteins metabolism, Peptide Nucleic Acids
- Abstract
Repetitive sequences are among the most unstable regions in the eukaryotic genome and defects in their maintenance correlate with premature aging and cancer development. Promyelocytic leukemia protein (PML) induces accumulation of proteins at distinct nuclear sites, thereby affecting a plethora of processes including DNA repair or maintenance of telomeres. Doxorubicin, the broadly used chemotherapeutic compound, induces formation of PML-nucleolar associations (PNAs). Nevertheless, molecular factors affecting formation of PNAs are still largely unknown. Here we show that PNAs can accumulate ribosomal DNA (rDNA) and, after restoration of RNA polymerase I activity, these structures transfer a fraction of rDNA outside the nucleolus. Mutagenesis of PML isoforms revealed that this process depends on the SUMO-interacting motif and adjacent serine-rich region, and is enhanced by exon8b present exclusively in PML IV isoform. Moreover, we demonstrate that PNAs formation is also regulated by p14ARF/p53 tumor suppressors and casein kinase 2. Our data elucidate how PML nucleolar compartment is assembled, bring the first evidence of PML interacting with rDNA, and show the PML-dependent translocation of rDNA away from the nucleolus., (Copyright © 2022 Elsevier B.V. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
5. Kinetic constant variability in bacterial oxidation of elemental sulfur.
- Author
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Pokorna B, Mandl M, Borilova S, Ceskova P, Markova R, and Janiczek O
- Subjects
- Bioreactors, DNA, Bacterial chemistry, DNA, Bacterial genetics, DNA, Ribosomal chemistry, DNA, Ribosomal genetics, Kinetics, Molecular Sequence Data, Oxidation-Reduction, RNA, Bacterial genetics, RNA, Ribosomal, 16S genetics, Sequence Analysis, DNA, Acidithiobacillus metabolism, Sulfur metabolism
- Abstract
Wide ranges of growth yields on sulfur (from 2.4 x 10(10) to 8.1 x 10(11) cells g(-1)) and maximum sulfur oxidation rates (from 0.068 to 1.30 mmol liter(-1) h(-1)) of an Acidithiobacillus ferrooxidans strain (CCM 4253) were observed in 73 batch cultures. No significant correlation between the constants was observed. Changes of the Michaelis constant for sulfur (from 0.46 to 15.5 mM) in resting cells were also noted.
- Published
- 2007
- Full Text
- View/download PDF
6. Use of immobilized cytochrome c as a ligand for affinity chromatography of thiosulfate dehydrogenase from Acidithiobacillus ferrooxidans.
- Author
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Janiczek O, Pokorna B, Zemanova J, and Mandl M
- Subjects
- Ligands, Protein Binding, Acidithiobacillus enzymology, Chromatography, Affinity, Cytochromes c metabolism, Enzymes, Immobilized metabolism, Oxidoreductases isolation & purification
- Abstract
Three matrices were used for immobilizing the cytochrome c: Sepharose CL-4B, Silasorb SPH amine and a laboratory-prepared new matrix based on crosslinked triazine (2,4,6-tris(aminoethylamine)-1,3,5-triazine) (TAT). Cytochrome c was immobilized on the matrices by several procedures and the amount of incorporated cytochrome c was determined. Cytochrome c immobilized on Sepharose CL-4B with periodate activation, cytochrome c immobilized on Silasorb-amine with carbodiimide activation and cytochrome c immobilized on crosslinked triazine were suitable for purification of thiosulfate dehydrogenase from Acidithiobacillus ferrooxidans. The yield with all matrices was about 90%. The purification factor of the above matrices was about 15. A new matrix based on TAT with cytochrome c represented a suitable way for thiosulfate dehydrogenase purification.
- Published
- 2005
- Full Text
- View/download PDF
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