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N Engl J Med. 2017 Apr 20;376(16):1527-1539. doi: 10.1056/NEJMoa1701488. Epub 2017 Mar 17.

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients.

Collaborators (1609)

Conde D, Colquhoun D, Missault L, Grégoire J, Gao R, Urina M, Solar M, Jensen HK, Grobbee D, Savolainen M, Schiele FN, Montalescot G, Edes I, Blake G, Lotan C, Maggioni A, Savonitto S, Lee CW, Leiva Pons JL, Dan GA, Cortada JB, Mellbin L, Kahan T, Noble S, Hwang JJ, Sritara P, Tökgozoğlu L, Tarasenko L, Borer JS, Black H, Carmena R, Furie KL, McMurray J, Neaton J, Zannad F, O’Neill B, Welty F, McNamara R, Chun H, Abbott JD, Jacoby D, McPherson C, Jadbabaie F, Pinto D, McCullough L, Silverman IE, Sansing LH, Dearborn-Tomazos J, Foody J, Schindler J, Piazza G, Chakrabarti A, Pride Y, Gelfand E, Baultrukonis D, Chaudhuri S, Frederich R, Johnson M, Mridha K, Powell C, Wang E, Wei C, Anderson P, Buonanno M, Epsley C, Evans B, Frolova M, Goetsch M, Hessinger D, Ikehara E, Ivanac K, Kizko J, Le K, McNally-Dufort C, Morocco T, Nadkarni S, Nissen T, Nye R, Pak R, Pence D, Redifer P, Schwartz W, Sattler C, Schade R, Sullivan B, Wegner J, Alvarez CA, Budassi N, Vogel DR, Avaca H, Conde DG, Estol CC, Gelersztein E, Glenny JA, Hershson AR, Bruno RL, Maffei LE, Soler JM, Zaidman CJ, Carnero GS, Colombo HR, Jure HO, Luquez HA, Ramos HR, Resk JH, Rusculleda MM, Ulla MR, Caccavo A, Farias EF, Wenetz LM, Cabella PR, Cuadrado JA, Chahin M, Mackinnon IJ, Zarandon RB, Schmidberg J, Fernandez AA, Montana O, Codutti OR, Gorosito VM, Maldonado N, Sala J, De La Fuente RA, Casabella TE, Di Gennaro JP, Guerrero RA, Alvarez MS, Berli M, Botta CE, Montenegro EE, Vico ML, Begg A, Lehman R, Gilfillan CP, d'Emden M, Markovic TP, Sullivan D, Aroney C, Stranks SN, Crimmins DS, Arstall M, Van Gaal W, Davis T, Aylward PE, Amerena J, William M, Proietto J, Purnell PW, Singh B, Arya KW, Dart AM, Colquhoun D, Thompson P, Davis SM, Carroll PA, De Looze F, Jayasinghe R, Bhindi R, Buysschaert I, Sarens T, van de Borne P, Scott BP, Roosen J, Cools F, Missault LH, Debroye C, Schoors DF, Hollanders G, Schroe HH, De Sutter J, Hermans K, Carlier M, van Landegem P, Verwerft J, Mulleners T, Delforge MD, Soufflet V, Elegeert I, Descamps OS, Janssens S, Lemmens RC, Desfontaines P, Scheen A, Heijmans S, Capiau L, Vervoort G, Carlier SG, Faes D, Alzand B, Keuleers S, De Wolf L, Thoeng J, De Bruyne L, de Santos MO, Felicio JS, Areas CA, Figueiredo EL, Michalaros YL, Neuenschwander FC, Reis G, Saad JA, Kormann AP, Nascimento CV, Precoma DB, Abib E Jr, dos Santos FR, Mello YG, Saraiva JF, Rech RL, Cerci R, Fortes JA, Rossi PR, de Lima e Silva FA, Hissa M, Silva RP, de Souza WK, Guimarães Filho FV, Mangili OC, de Oliveira Paiva MS, Tumelero R, Abrantes JA, Caramori PR, Dutra OP, Leaes PE, Manenti ER, Polanczyk CA, Bandeira e Farias FA, de Moraes Junior JB, Russo LA, Alves AR Jr, Dracoulakis MD, Ritt LE, Saporito WF, Herdy AH, Maia LN, Sternieri MV, Ayoub JC, Bianco HT, da Costa FA, Eliaschewitz FG, Fonseca FA, Nakandakare ER, Bonansea TC, Castro NM, de Barros e Silva PG, Smith P, Botelho RV, Resende ES, Barbieri DS, Hernandes ME, Bajaj H, Beaudry P, Berlingieri JC, Salter TJ, Ajala B, Anderson TJ, Nanji A, Ross S, Pandey S, Desrosiers D, Gaudet D, Moran G, Csanadi MA, St-Amour E, Cusimano S, Halperin FA, Babapulle M, Vizel S, Petrella J, Spence JD, Gupta N, Tellier G, Bourgeois R, Gregóire JC, Wesson T, Zadra R, Twum-Barima DY, Cha JY, Hartleib MC, Bergeron J, Chouinard G, McPherson TP, Searles G, Peterson SR, Mukherjee A, Lepage S, Conway JR, Kouz SM, Dion D, Pesant Y, Cheung SS, Goldenberg RM, Aronson R, Gupta AK, O’Mahoney M, Pliamm L, Teitelbaum I, Hoag GN, Nadra IJ, Yared Z, Yao LC, Nguyen T, Saunders KK, Potthoff S, Varleta P, Assef V, Godoy JG, Olivares C, Roman O, Vejar M, Montecinos H, Pincetti C, Li Y, Wang D, Li J, Yang X, Du Y, Wang G, Yang P, Zhang X, Xu P, Zhao Y, Chen J, Li S, Li W, Zhang L, Zhu Y, Zhang Y, Zhou C, Wang Y, Liu F, Ma Y, Ti Z, Zeng X, Zhou Y, Cui G, Li D, Xue L, Jiang J, Lian Y, He Y, Mendoza JA, Bonfanti JA, Dada FA, Urina-Triana MA, Rodriguez WR, Sanchez ML, Lozno HY, Triana EH, Arambula RM, Rico-Carrillo AE, Gallo HJ, Catano JS, Jattin FG, Plazas JA, Gomez JE, Botero-Lopez R, Gomez NI, Munoz CF, Pelaez SV, Eraso AM, Goyes AR, Elbl L, Fiserova N, Vesely J, Wasserburger B, Blaha V, Vojacek J, Maskova P, Hutyra M, Vrkoc J, Hala T, Vodnansky P, Bocek P, Cifkova R, Bufka V, Ceska R, Machkova M, Zidkova E, Lukac M, Mikusova T, Kellnerova I, Kuchar L, Ferkl R, Cech V, Zemek S, Monhart Z, Davidsen F, Joensen A, Lihn AS, Rasmussen TK, Wiggers H, Lindgren LM, Schmidt U, Galatius S, Sillesen H, Bronnum Schou J, Thomsen KK, Urhammer S, Jeppensen J, Schou M, May O, Steffensen R, Nielsen WB, Nielesen T, Jepsen JM, Rai A, Sykulski R, Andersen LT, Rickers H, Frost L, Lomholdt J, Egstrup K, Wermuth S, Klausen L, Lassus J, Palomaki A, Khari J, Tatlisumak T, Kekki S, Vanttinen E, Strandberg A, Valtonen M, Sia SM, Nerg O, Puhakka M, Savolainen M, Strand J, Timonen M, Levola J, Arstila L, Taurio J, Kantola I, Suomi J, Humaloja K, Askonen K, Schiele F, Sibon I, Zemour G, Goube P, Petit C, Chati Z, Range G, Rabahi F, Rihani R, Bergerot C, Roubille F, Boye A, Probst V, Ferrari E, Cayla G, Thouvenot E, Delarche N, Couffinhal T, Coisne D, Paillard F, Elbaz M, Decoulx E, Angoulvant D, Agraou B, Caudmont S, Berrouschot J, Lauer B, Schoell I, Trenk D, Derwahl KM, Khariouzov A, Proepper F, Stawowy P, Da Stephan U, Stoessel J, Voehringer HF, Dorsel T, Stellbrink C, Rinke A, Northroff J, Bourhaial H, Stratmann M, Wetzel T, Axthelm C, Guenzel A, Weigmann I, Faghih M, Hagemann D, Schaefer A, Weber D, Luedemann J, Contzen C, Kornmann MO, Winkelmann B, Simon J, Felix S, Brauer C, Laufs U, Schmidt E, Marten I, Licka M, Heisters J, Appel KF, Kleinecke-Pohl U, Klein C, von Hodenberg EF, Maus O, Sigal H, Taeschner H, Schwimmbeck P, Lemke B, Perings C, Illies G, Pfuetzner A, Salbach P, Hengstenberg C, Kohler A, Mudra H, Behnke T, Baar M, Jeserich M, Scholz G, Naudts I, Voller H, Herrmann HJ, von Engelhardt CB, Gerke S, Pohlmeier L, Schaufele T, Woehrle J, Al-Zoebi A, Horacek T, Peterfai E, Kemeny V, Lakatos F, Bod E, Andrassy P, Andreka P, Balo T, Davidovits Z, Laszlo Z, Nagy K, Papp A, Somogyi A, Toldy-Schedel E, Vertes A, Voros P, Paragh G, Martyin T, Edes I, Hajdu C, Deak L, Farago K, Nagy A, Kirschner R, Koszegi Z, Zilahi Z, Toth K, Wittmann I, Bajcsi D, Reiber I, Toth L, Benczur B, Nagy L, Sydo T, Lupkovics G, Oroszlan T, Crean P, Mahon NG, McAdam B, MacNeill B, Katz A, Tsalihin D, Vazan A, Eitan A, Lewis BS, Gavish D, Wainstein J, Lotan C, Mosenzon O, Mosseri M, Vishlitzky V, Atar S, Nseir WB, Brenner H, Elis A, Fuchs S, Shimon I, Solodky A, Goldhaber A, Tanne D, Knobler H, Kracoff OH, Hussein O, Auriel E, Chorin E, Sharir T, Bitzur R, Shechter M, Antonicelli R, Franceschini E, Porcu M, Sesti G, Savonitto S, Maggiolini S, Salvioni A, Filardi PP, Trimarco B, Averna M, Pasqualini L, Pirro M, Pantaleoni M, Piovaccari G, Arca M, Fedele F, Roncon L, Anselmi M, Sganzerla P, Morocutti G, Bonora E, Dimas AL, Esperon GA, Morales-Villegas E, Isunza JM, Beltran LG, Molina CA, Garcia DK, Ruiz LA, Reyna LS, De los Rios Ibarra MO, Soto JR, Gonzalez-Ortiz M, Herrera-Marmolejo M, Ramos SA, Ramos-Lopez GA, Stobschinski CA, AguilarSalinas CA, Alpizar-Salazar M, Jimenez-Sanchez M, Sanchez Mijangos JH, Elizondo Moreno ER, Garcia Castillo A, Garcia Hernandez PA, Gonzalez-Gonzalez JG, Riojas Charles CM, Valdez Lopez HG, Nuriulu Escobar PL, Lechuga Martin del Campo A, Castro Montes BE, Mendez Bucio A, Leiva Pons JL, Rodriguez-Briones I, Torre Amione G, Violante Ortiz R, Luna Ceballos RI, Lopez Rosas E, Bax WA, Alhakim M, van de Wiel A, Liem SS, Groutars RG, Herrman JP, Hovingh GK, van de Wetering ML, van Royen N, Groenemeijer BE, Hoedemaker G, Schaap J, Ronner E, Angun M, Mairuhu AT, Van Alem AP, Martens FM, Heijmeriks JA, van Hal JM, Schoofs MW, den Hartog FR, Kentgens S, Post JC, Louwerenburg JW, van Rossum P, Viergever EP, Donders SH, Kamphuisen PW, van Beek E, Nijmeijer R, Lenderink T, Schreuder T, Kuijper AF, The SH, Van het Hof-Wiersma JJ, Tichelaar P, Westerndorp I, Breedveld RW, Karalis I, Romer TJ, Bogaard K, Van Koningsbruggen P, Kroon AA, Hoogslag PA, Rensing BJ, Cramer E, Remmen JJ, Riksen NP, Bokern MJ, Cabezas MC, Mulder H, Nierop PR, van Kempen WW, Zoet-Nugteren SK, van Daele ME, Swart HP, van der Zwaan CT, Hermans WR, Magro M, van de Wal RM, Hassink RJ, Visseren F, Veenendaal A, De Nooijer C, Troquay RP, Imholz BP, van der Meer P, Visser RP, van Leendert RJ, Gosselink MA, Baker J, Benatar JR, Kerr J, Pryke JR, Scott RS, Millar-Corte GD, Williams M, Montgomery B, Venter DJ, Ternouth IF, DeCaigney SC, Hart HH, Corin A, Garden PI, Sheahan D, Harding SA, Korecki J, Supronik J, Styczkiewicz M, Bijata-Bronisz R, Rusicka T, Walczak M, Krolikowski Z, Ostrowski J, Lukaszewicz M, Przekwas-Jaruchowska M, Zieba B, Miekus P, Orkwiszewska-Nalewajko A, Piepiorka M, Kubalski P, Wychota K, Blach E, Ochala A, Okopien B, Wronska D, Janion M, Czarnecka D, Kolodziejczyk J, Konieczynska M, Landa K, Mirek-Bryniarska E, Necki M, Pasternak DA, Rozpondek P, Trebacz J, Walczewska J, Sidor M, Broncel M, Drozdz J, Kosmider M, Saryusz-Wolska M, Kucharska D, Opalinska E, Pijanowski Z, Wozniak I, Banaszkiewicz K, Klecha A, Horodecki M, Piskorz-Wapinska J, Kobielusz-Gembala I, Kim MH, Kim DK, Cho BR, Kim KS, Her SH, Lee SY, Rhee MY, Kim K, Kang WC, Kim DH, Cho YS, Kim SH, Lee CW, Rim SJ, Tahk SJ, Jeon HK, Yoon J, Mociran M, Pop CF, Minescu B, Andrei LD, Radoi M, Calin A, Ciomag RM, Copaci I, Dan GA, Fruntelata AG, Popescu M, Tivadar S, Roman G, Avram RI, Mistodie CV, Morosanu M, Popa AR, Popescu ML, Popoviciu MS, Tase A, Busegeanu M, Popescu A, Szilagyi I, Sitterli-Natea CN, Maximov DM, Munteanu M, Negrisanu GD, Kuzin A, Popov D, Shapovalova J, Vishneva E, Shutemova E, Pasechnik E, Bogdanov E, Khasanov N, Barbarash OL, Shangina OA, Tarasov N, Solonev O, Kosmacheva E, Chernyatina MA, Ginzburg M, Blokhin A, Bulanova N, Drapkina OM, Gordeev IG, Libov IA, Lomakin N, Panchenko E, Shogenov ZS, Zateyshchikov D, Klein G, Motylev I, Belenkiy DI, Demin A, Nikolaev KY, Oleynikov V, Zrazhevskiy K, Katelnitskiy I, Khaisheva L, Aksentiev S, Nedoshivin A, Popova VB, Agafina AS, Ballyuzek M, Baranova E, Burova N, Eryshev S, Filippov A, Goloshchekin BM, Konstantinov V, Kostenko VA, Simanenkov VI, Volkova A, Duplyakov D, Reshetko O, Shvarts Y, Kuznetsov VA, Samoylova YG, Tolkacheva V, Shalaev SV, Khokhlov AL, Malygin A, Shilkina NP, Yakusevich VV, Margoczy R, Zubek V, Dzupina A, Dubrava J, Dulkova K, Fabryova L, Gaspar L, Kamensky G, Kokles M, Raslova K, Soosova I, Stevlik J, Strbova J, Sumbal J, Uhliar R, Micik J, Truban J, Fedacko J, Pastrnakova E, Pella D, Fazekas F, Ambrovicova V, Kycina P, Martinka E, Nociar J, Belicova M, Banik M, Kanderkova D, Hranai M, Duris T, Krahulec B, Benacka J, Vinanska D, Roskova E, Skripova D, Macek V, Vohnout B, Buganova I, Engelbrecht JM, Pretorius MM, Ebrahim IO, Bayat J, Ganesh S, Ranjith N, Coetzer TF, Jacovides A, Distiller LA, Hellig FS, Engelbrecht IV, Mahomed AA, Blignault SC, Burgess LJ, Kotze HJ, van Nieuwenhuizen E, Musungaie DB, Emanuel S, van der Walt E, Pretorius CE, Roos JS, Roux SM, Badat AE, Fouche L, Vahed YA, Jansen van Resburg D, van Zyl LJ, Soto Gonzalez A, Diaz JL, Segura T, Botella Serrano M, Botas Rodrigues J, Molto-Jorda JM, Dominguez Escribano JR, Sogorb Garri F, Blanco Coronado JL, Gaztambide Saenz MS, Brotons Cuixart C, Bruguera Cortada J, Garcia-Moll Marimon X, Gonzalbez Morgaez JD, Maisterra Santos O, Roquer Gonzalez J, Sobrino-Martinez J, Chueca Fernandez JE, Narejos S, Suarez Garcia S, Perez Martinez P, Figueras Camos R, Medrano Martinez V, Bellido Guerrero D, Martinez Deben F, Vila Belmonte A, Mediavilla Garcia JD, Romero Hinojosa JA, Martorell Mateu E, Cequier Fillat AR, Pinto Sala X, Adroer Martori R, Bueno Diez M, Lopez Cano C, Worner Diz F, Gonzalez Juanatey C, Alvarez-Sala Walther LA, De Dios Garcia Diaz J, Garcia Puig J, Jodar Gimeno E, Plaza Perez I, Suarez-Fernandez C, Tunon J, Zamorano Gomez JL, Brito Sanfiel MA, Escudier Villa JM, de Mora Martin M, Dominguez Lopez M, Hernandez Garcia JM, Tinahones Madueno FJ, Perez Paredes M, Aracil Villar J, Barreda Gonzalez MJ, Ripoll Vera TV, Tofe Povedano S, Sanchez Alvarez J, Martinez Via L, Robles Iniesta A, Masana L, Vinyoles Bargallo E, Calvo Gomez C, Gonzalez Juanatey JR, Cruz Fernandez JM, De La Cuesta Mayor C, Duran Garcia S, Jimenez Hernandez MD, Morales Portillo C, Muniz Grijalvo O, De Castro R, Taverna Llaurado E, Pons Amate JM, Terns Riera M, Civeira Murillo F, Linderfalk C, Curiac D, Saldeen-Nilehn K, Koskinen P, Khalili P, Tortensson I, Lindholm CJ, Luts A, Koskinen PT, Gottsater A, Persson BE, Mooe T, Larnefeldt H, Boman K, Mellbin L, Crisby M, Kahan T, Rasmanis G, Tengmark BO, Witt N, Hagstrom E, Viklund J, Muller C, Mach F, Burnier M, Nanchen D, Wuerzner G, Banyai M, Moccetti T, Miserez AR, Bilz S, Weber K, Lai WT, Chang KC, Ueng KC, Tsai WC, Chiang CE, Hou C, Hwang JJ, Pei D, Krittayaphong R, Kiatchoosakun S, Srimahachota S, Boonyavarakul A, Sritara P, Jintapakorn W, Gullu H, Onrat E, Erkan AF, Demirci D, Sari R, Ceyhan C, Ari H, Araz M, Degertekin M, Goktekin O, Uresin AY, Yigit Z, Akdeniz B, Comlekci A, Kayikcioglu M, Sahin T, Ozcan T, Durakoglugil E, Asamoah-Owusu N, Reed R, Bakhai A, Dixon L, Sharma R, Avornyo AA, Jones AF, Lip G, Clark R, Banerjee M, Wakeling J, Arden C, Blagden MD, Walukiewica P, Marshall A, Maxwell TG, Gunstone AE, Kadr HH, Patle R, Arif I, Jhund PS, McKaig G, Douglas F, Mierzejewski L, Turner W, Sathyapalan T, Ivan P, Manoj A, Rice S, Collier DJ, Nair DR, Thom S, Fiore G, De Belder M, Price D, Sobolewska J, Martin S, Takhar A, Moriarty A, Kondagunta V, Myhill T, Gibson JM, Cecil JT, Halcox J, Annamalai N, Gorog DA, McCormack T, Pegge N, Field A, Adams F, Klein JJ, Busch RS, Bretton EM, Jaffrani N, Salacata A, Assadourian A, Gogia HS, Dyke CK, Rubenfire M, Essandoh LK, Welker JA, Ledesma G, Lupovitch S, Delgado JP, Hendrix EL, Quyyumi AA, Riesenberg RA, Robertson DG, Weinstein DL, Weiss R, Casaubon L, Gammon RS, Brar HS, Bittar GD, Guarnieri TT, Ince CS Jr, Quraishi AM, Saeed S, Albert M, Sotolongo RP, Bernard JV, Karlsbergg RP, Lepor NE, Kirby WE, McLean B, Miller AP, Ovalle F, Townsend JC, Beckett PL, Eaves WB, West SH, Kosinski EJ, Zarich SW, Mahal SS, Maw K, Maynard KM, Chen JC, Gelormini J, Gottlieb DW, Gabra NW, Narayan P, Sparks J, Field JC, Willits VL, O’Steen MB, Pasquini JA, Sensebrenner JW, Yarows SA, Hiotis L, Jagielo TJ, Levinson DJ, Diller PM, Kereiakes DJ, Turner TA, Vincent S, Camp AD, Denker PS, Manning MB, Rocco MB, Stamps HB, Strader JR, Uusinarkaus KT, Kennett JD, Leichter SB, McNeil DL, Schumacher DR, Chang AR, Ellison HS, Updegrove JD, Hamroff GS, Kay JS, Marar IE, Flores E, Saini S, Abdullah S, Berk MR, Fordan S, Joshi PH, McCullough PA, Reynolds RD, Rosenstock J, Sachson RA, Shammas N, Fishbein GJ, Randall WJ, Henderson DA, Nash ML, Barker BA, Cohen SS, Seidman B, Odekirk LL, Grillo RS, Martinez LM, Multani P, Alwine LK, McGarvey JF, Mollerus ME, Miller AB, Kotek LW, Changlani M, Zavaro SH, Munoz F, Mehta PM, Helm RJ, Farhat NZ, Farsad R, Raoof TJ, Shultz JH, Geohas JG, Allaw MA, Dela Llana A, Gutmann JE, Inzerello AT, Alappat P, George AR, Haddad TM, Lillestol MJ, Grodman R, Peniston JH, Wadud K, Garcia B, Hamilton ME, Lerman S, Perloff DE, Graff A, Saxena S, Alvarado OP, Malik A, Reddy RD, Kinzfogl G, Cornett GM, Norwood PC, Gilbert JM, Willis JG, McGrew F, Sharma S, Castro MA, Cucher FH, Altafullah IM, Khurana S, Knutson TJ, Kinnaman SJ, Stuckey T, Pudi KK, Mayfield RK, Funk GS, Nixon WA, Dor I, Boyett BE, Srivastava S, Elosegui AM, Isserman SM, Cheek HB, Promisloff SD, Tami LF, Zeig S, fitz-Patrick D, Dave KN, Ahmad A, Arain S, Ballantyne CM, Doshi A, El Hafi SE, Feldman J, Fragoso VG, Gilford T, Hoffman AS, Pouzar JE, Vivekananthan K, Ansari SH, Strzinek RA, Crater TA, Robinson JG, Fulmer JJ, Patel AM, Pereira ES, Stich MA, Sultan S, Geskin G, Ruoff GE, Gillespie E, Bybee KA, Moriarty PM, Savin V, Agaiby JM, Melucci MB, Jantzi CM, Davidson E, Smith WB, Treasure CB, Wakefield PH, Deck K, Edris MA, Gilmore RM, Seep MK, Andersen JL, Detweiler RO, Rosenfeld JC, Strobl DJ, Steinhoff JP, Adams A, Estevez R, Molin CJ, Kim CY, Dy J, Fox KE, Farris NR, Wayne JD, Whitney RT, Randhawa PM, Mego DM, MacDolnald L, Caputo RP, Rigolosi R, VanNatta B, Pacheco TR, El-Shahawy M, Gonzalez EJ, Guice MJ, Cherlin RS, Bays HE, Shoukfeh M, Morris FH, Loy J, Vora SK, Staab PK, Frisoli A, Kimmel MA, Cohen AJ, Green CB, Whitlock L, Butuk DJ, McCartney MJ, Ables LR, Acosta R, Alvarez JG, Barrera CM, Benitez O, Berenguer RA, Breton CF, Chiong R, Delgado MI, Dufreny A, Fialkow JA, Franczek S, Frias JJ, Iglesias C, Landron-Garcia L, Llerena SN, Martinez RF, Miranda AA, Morytko JA, Rodriguez IJ, Sotolongo R, Suarez-Sarmiento A, Terrelonge AE, Vaca CE, Venereo JM, Verdeza C, Zeno ML, Chilka S, Felten WR, Hartman AN, Shayani SS, Duprez D, Knickelbine T, Chambers JD, Cone CL, Broughton R, Napoli MC, Seaton BL, Smith SK, Reedy MA, Kesani MK, Nicol PR, Stringam SO, Talano JV, Barnum O, Desai V, Montero M, Jacks RK, Kostis JB, Owen JG, Makam SK, Grosman I, Underberg JA, Masri BE, Peters SS, Serje J, Lenhard MJ, Glover R, Paraboschi CF, Lim EH, Connery L, Kipgen W, Bravo P, DiGiovanna MJ, Tayoum H, Gabriel JD, Ariani MK, Robinson MF, Clemens PC, Corder CN, Schifferdecker B, Tahirkheli NK, Hurling RT, Rendell MS, Shivaswamy V, Madu IJ, Dahl CF, Ayesu K, Kim C, Barettella MB, Jamidar HA, Bloom SA, Vora KN, Ong ST, Aggarwala G, Sack G, Blaze K, Krichmar P, Murcia A, Teltser M, Villaman-Bencosme Y, Fahdi IE, Williams DG, Lain EL, Garcia HL, Karim SN, Francyk DM, Gordon MB, Palchick BA, McKenzie ME, Gimness MP, Greiff J, Ruiz-R L, Vazquez-Tanus JB, Schlager D, Connelly T, Soroka E, Hastings WL, O’Dea DJ, Purdy DA, Jackson B, Arcanese ML, Strain JE, Schmedtje JF Jr, Davis MG, A A, Prasada S, Scott DL, Vukotic G, Akhtar N, Larsen DC, Rhudy JM, Zebrack JS, Bailey SR, Grant DC, Mora A, Perez JA, Reyes RG, Sutton JC, Brandon DM, First BP, Risser JA, Claudio J, Figueroa-Cruz WL, Sosa-Padilla MA, Tan AE, Traboulssi MA, 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Plowchalk D, Sasson S, Skaggs J, Sweeney K, Vincent J.

Abstract

BACKGROUND:

Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk.

METHODS:

In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months.

RESULTS:

At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P=0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P=0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P=0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001).

CONCLUSIONS:

In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients. (Funded by Pfizer; SPIRE-1 and SPIRE-2 ClinicalTrials.gov numbers, NCT01975376 and NCT01975389 .).

PMID:
28304242
DOI:
10.1056/NEJMoa1701488
[Indexed for MEDLINE]
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