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2. Efficacy and safety of initial combination therapy with amlodipine/valsartan compared with amlodipine monotherapy in black patients with stage 2 hypertension: the EX-STAND study
- Author
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Flack, J M, Calhoun, D A, Satlin, L, Barbier, M, Hilkert, R, and Brunel, P
- Published
- 2009
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3. 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, 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 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 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 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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, 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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 C, Burke W, Burley T, Burton C, Burtt D, Byars W, Caballero-Valiente B, Carr K, Halliwell TC, Castillo J, Cei L, Cerda L, Chambers J, Chamblee T, Chattin W, Chee L, Chen YC, 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 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, 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Hodnett P, Hoffman M, Hogan C, Holmes Z, Rees DH, 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, Lee K, 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 JM, Madder R, Magness K, Maheshwari A, Alan A, Malek M, Maletz L, Malhotra V, Malhotra S, Mandviwala M, Mani CK, 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 BA, 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 JM, 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 R, Patel M, Patel S, Paysor C, Pena A, Pereira S, Perez M, Perez A, Perkins H, Perry B, Peters P, Phillippi C, Phillips A, Phillips A, Piacente R, Pintado M, Pish R, Pitt W, Poling T, Pomposini 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M., Everett, B. M., Thuren, T., Macfadyen, J. G., Chang, W. H., Ballantyne, C., FONSECA E PIRES, CARLOS EDUARDO, 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, CANTOS Trial, Group, Perrone, Filardi, P, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, and ACS - Atherosclerosis & ischemic syndromes
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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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4. 358Understanding and mitigating the risk of infection with canakinumab
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Libby, P, primary, Glynn, R, additional, Thuren, T, additional, Hilkert, R, additional, and Ridker, P, additional
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- 2018
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5. COMBINATION ALISKIREN+AMLODIPINE IS MORE EFFECTIVE THAN AMLODIPINE MONOTHERAPY IN MALE AND FEMALE AFRICAN AMERICAN SUBJECTS WITH STAGE 2 HYPERTENSION: PP.5.186
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Black, H, primary, Weinberger, M, additional, Purkayastha, D, additional, Lee, J, additional, Israel, M, additional, Hilkert, R, additional, and Izzo, J, additional
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- 2010
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6. COMBINATION ALISKIREN+AMLODIPINE PROVIDES GREATER BLOOD PRESSURE REDUCTION THAN AMLODIPINE ALONE IN AFRICAN AMERICANS WITH STAGE 2 HYPERTENSION AND OBESITY OR METABOLIC SYNDROME: PP.5.173
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Weinberger, M, primary, Izzo, J, additional, Purkayastha, D, additional, Lee, J, additional, Israel, M, additional, Hilkert, R, additional, and Black, H, additional
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- 2010
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7. INTENSIVE TREATMENT WITH COMBINATION AMLODIPINE/VALSARTAN VS MODERATE THERAPY FOR HYPERTENSIVE PATIENTS WITH DIABETES OR CKD UNCONTROLLED ON ARB MONOTHERAPY: PP.17.149
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Sowers, J, primary, Giles, T, additional, Ofili, E, additional, Pitt, B, additional, Seifu, Y, additional, Samuel, R, additional, Hilkert, R, additional, and Oparil, S, additional
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- 2010
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8. TRIPLE COMBINATION THERAPY WITH AMLODIPINE/VALSARTAN/HCTZ AT MAXIMAL DOSES IS SAFE AND EFFECTIVE FOR HYPERTENSIVE PATIENTS UNCONTROLLED ON ARB MONOTHERAPY: THE EXTRA STUDY: PP.5.216
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Oparil, S, primary, Giles, T, additional, Ofili, E, additional, Pitt, B, additional, Seifu, Y, additional, Samuel, R, additional, Hilkert, R, additional, and Sowers, J, additional
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- 2010
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9. INTENSIVE TREATMENT WITH COMBINATION AMLODIPINE/VALSARTAN PROVIDES GREATER EFFICACY VS MODERATE TREATMENT FOR HYPERTENSIVE PATIENTS UNCONTROLLED ON ARB MONOTHERAPY: THE EXTRA STUDY: PP.5.208
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Oparil, S, primary, Giles, T, additional, Ofili, E, additional, Pitt, B, additional, Seifu, Y, additional, Samuel, R, additional, Hilkert, R, additional, and Sowers, J, additional
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- 2010
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10. RACE/ETHNIC DIFFERENCES IN ANTIHYPERTENSIVE RESPONSE TO MODERATE VS INTENSIVE DOSE OF COMBINATION AMLODIPINE/VALSARTAN IN PATIENTS UNCONTROLLED ON ARB MONOTHERAPY: PP.5.204
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Ofili, E, primary, Oparil, S, additional, Giles, T, additional, Pitt, B, additional, Seifu, Y, additional, Samuel, R, additional, Hilkert, R, additional, and Sowers, J, additional
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- 2010
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11. ALISKIREN+AMLODIPINE COMBINATION REDUCES CENTRAL BLOOD PRESSURE MORE THAN AMLODIPINE ALONE IN AFRICAN AMERICANS WITH STAGE 2 HYPERTENSION: PP.5.171
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Izzo, J, primary, Weinberger, M, additional, Israel, M, additional, Hilkert, R, additional, Purkayastha, D, additional, Lee, J, additional, and Black, H, additional
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- 2010
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12. INTENSIVE DOSE OF COMBINATION AMLODIPINE/VALSARTAN PROVIDES IMPROVED 24-H BP RESPONSE COMPARED TO MODERATE DOSE IN HYPERTENSIVE PATIENTS UNCONTROLLED ON ARB MONOTHERAPY: PP.5.211
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Giles, T, primary, Oparil, S, additional, Ofili, E, additional, Pitt, B, additional, Seifu, Y, additional, Samuel, R, additional, Hilkert, R, additional, and Sowers, J, additional
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- 2010
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13. GREATER EFFICACY WITH AMLODIPINE/VALSARTAN COMBINATION INTENSIVE VS MODERATE TREATMENT FOR HYPERTENSIVE PATIENTS WITH CARDIOMETABOLIC SYNDROME UNCONTROLLED ON ARB MONOTHERAPY: PP.34.432
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Sowers, J, primary, Giles, T, additional, Ofili, E, additional, Pitt, B, additional, Seifu, Y, additional, Samuel, R, additional, Hilkert, R, additional, and Oparil, S, additional
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- 2010
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14. COMBINATION ALISKIREN+AMLODIPINE PROVIDES GREATER REDUCTIONS IN CLINIC AND 24-HOUR AMBULATORY BLOOD PRESSURES THAN AMLODIPINE ALONE IN AFRICAN AMERICANS WITH STAGE 2 HYPERTENSION: PP.5.187
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Black, H, primary, Weinberger, M, additional, Purkayastha, D, additional, Lee, J, additional, Israel, M, additional, Hilkert, R, additional, and Izzo, J, additional
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- 2010
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15. Comparative efficacy and safety of amlodipine/benazepril combination therapy and amlodipine monotherapy in severe hypertension
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Izzo, J L, primary, Purkayastha, D, additional, Hall, D, additional, and Hilkert, R J, additional
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- 2009
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16. TWO DRUG CLASS ANTI-HYPERTENSIVE THERAPY AND CARDIOVASCULAR OUTCOMES IN OLDER WOMEN
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Wassertheil-Smoller, S., primary, Psaty, B., additional, Greenland, P., additional, Margolis, K., additional, Oberman, A., additional, Kotchen, T., additional, Mouton, C., additional, Hilkert, R., additional, Black, H., additional, and Aragaki, A., additional
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- 2004
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17. The relationship between renal impairment and left ventricular structure, function, and ventricular-arterial interaction in hypertension.
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Shah AM, Lam CS, Cheng S, Verma A, Desai AS, Rocha RA, Hilkert R, Izzo J, Oparil S, Pitt B, Thomas JD, Zile MR, Aurigemma GP, Solomon SD, Shah, Amil M, Lam, Carolyn S P, Cheng, Susan, Verma, Anil, Desai, Akshay S, and Rocha, Ricardo A
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- 2011
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18. Moderate versus intensive treatment of hypertension with amlodipine/valsartan for patients uncontrolled on angiotensin receptor blocker monotherapy.
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Oparil S, Giles T, Ofili EO, Pitt B, Seifu Y, Hilkert R, Samuel R, Sowers JR, Oparil, Suzanne, Giles, Thomas, Ofili, Elizabeth O, Pitt, Bertram, Seifu, Yodit, Hilkert, Robert, Samuel, Rita, and Sowers, James R
- Published
- 2011
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19. Disulfide linkage of biotin identifies a 106-kDa Ca2+release channel in sarcoplasmic reticulum*
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Zaidi, N F, Lagenaur, C F, Hilkert, R J, Xiong, H, Abramson, J J, and Salama, G
- Abstract
Reactive disulfide reagents (RDSs) with a biotin moiety have been synthesized and found to cause Ca2+release from sarcoplasmic reticulum (SR) vesicles. The RDSs oxidize SH sites on SR proteins via a thiol-disulfide exchange, with the formation of mixed disulfide bonds between SR proteins and biotin. Biotinylated RDSs identified a 106-kDa protein which was purified by biotin-avidin chromatography. Disulfide reducing agents, like dithiothreitol, reverse the effect of RDSs and thus promoted active re-uptake of Ca2+and dissociated biotin from the labeled protein indicating that biotin was covalently linked to the 106-kDa protein via a disulfide bond. Several lines of evidence indicate that this protein is not Ca2+,Mg2+-ATPase and is not a proteolytic fragment or a subunit of the 400-kDa Ca2+-ryanodine receptor complex (RRC). Monoclonal antibodies against the ATPase did not cross-react with the 106-kDa protein, and polyclonal antibodies against the 106-kDa did not cross-react with either the ATPase or the 400-kDa RRC. RDSs did not label the 400-kDa RRC with biotin. Linear sucrose gradients used to purify the RRC show that the 106-kDa protein migrated throughout 5–20% linear sucrose gradients, including the high sucrose density protein fractions containing 400-kDa RRC. Protease inhibitors diisopropylfluorophosphate used to prevent proteolysis of 400-kDa proteins did not alter the migration of 106-kDa in sucrose gradients nor the patterns of biotin labeling of the 106-kDa protein. Incorporation of highly purified 106-kDa protein (free of RRC) in planar bilayers revealed cationic channels with large Na+(gNa+= 375 ± 15 pS) and Ca2+(gCa2+= 107.7 ± 12 pS) conductances which were activated by micromolar [Ca2+]freeor millimolar [ATP] and blocked by micromolar ruthenium red or millimolar [Mg2+]. Thus, the SR contains a sulfhydryl-activated 106-kDa Ca2+channel with apparently similar characteristics to the 400-kDa “feet” proteins.
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- 1989
- Full Text
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20. 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 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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 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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., 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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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
21. Disulfide linkage of biotin identifies a 106-kDa Ca2+ release channel in sarcoplasmic reticulum
- Author
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Zaidi, N F, primary, Lagenaur, C F, additional, Hilkert, R J, additional, Xiong, H, additional, Abramson, J J, additional, and Salama, G, additional
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- 1989
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22. Recurrent Hospitalizations and Response to Vericiguat in Heart Failure and Reduced Ejection Fraction.
- Author
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Mentz RJ, Stebbins A, Butler J, Chiang CE, Ezekowitz JA, Hernandez AF, Hilkert R, Lam CSP, McDonald K, O'Connor CM, Pieske B, Ponikowski P, Roessig L, Sweitzer NK, Voors AA, Anstrom KJ, and Armstrong PW
- Subjects
- Humans, Male, Female, Aged, Middle Aged, Peptide Fragments blood, Double-Blind Method, Treatment Outcome, Heterocyclic Compounds, 2-Ring, Heart Failure drug therapy, Heart Failure mortality, Heart Failure physiopathology, Stroke Volume physiology, Pyrimidines therapeutic use, Hospitalization statistics & numerical data, Natriuretic Peptide, Brain blood
- Abstract
Background: In VICTORIA (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction), vericiguat compared with placebo reduced cardiovascular death or heart failure (HF) hospitalization in patients with HF with reduced ejection fraction., Objectives: This study explored the association between vericiguat and recurrent hospitalizations and subsequent mortality after HF hospitalization., Methods: The treatment effect of vericiguat on the burden of HF hospitalizations was evaluated by assessing total HF hospitalization and cardiovascular death in the overall trial and based on baseline N-terminal pro-B-type natriuretic peptide levels with and without adjustment for VICTORIA model covariates (ie, baseline variables associated with the primary endpoint) assessed via the Andersen-Gill method. Associations between vericiguat and recurrent hospitalization and mortality adjusted for VICTORIA model covariates are reported., Results: There were 1,222 total HF hospitalizations and cardiovascular deaths among 2,526 patients in the vericiguat group and 1,336 total events among 2,524 patients in the placebo group (unadjusted HR: 0.89 [95% CI: 0.81-0.97] and adjusted HR: 0.92 [95% CI: 0.84-1.01]). In the subgroup with N-terminal pro-B-type natriuretic peptide levels ≤2,816 pg/mL (ie, Q1 and Q2; median or below), there was a suggestion of a benefit with vericiguat (adjusted HRs of 0.80 [95% CI: 0.64-1.01] and 0.77 [95% CI: 0.62-0.94], respectively) compared with those above this value (adjusted HRs of 1.12 [95% CI: 0.93-1.34] and 0.87 [95% CI: 0.74-1.04] for Q3 and Q4). There was no significant difference in treatment effect between patients with vs without an HF hospitalization. After HF hospitalization, the all-cause mortality rate (events per 100 patient-years) was 48.6 for vericiguat and 44.1 for placebo., Conclusions: Additional investigation of the association between vericiguat and cardiovascular death and total HF hospitalizations by recurrent event analysis did not show a statistically significant reduction in events. Mortality was high after HF hospitalization, emphasizing the need for further therapies to reduce morbidity and mortality. (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction [VICTORIA]; NCT02861534)., Competing Interests: Funding Support and Author Disclosures The VICTORIA trial was funded by Merck Sharp & Dohme Corp, a subsidiary of Merck & Company, Inc, and Bayer AG. Dr Mentz has received research support and honoraria from Bayer and Merck Sharp & Dohme Corporation, a subsidiary of Merck & Company, Inc. Dr Butler has received consulting fees from Abbott, Adrenomed, Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CVRx, G3 Pharmaceutical, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Roche, and Vifor. Dr Chiang has received honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, MSD, Novartis, Pfizer, and Sanofi. Dr Ezekowitz has received research grants and consulting fees from Bayer, Merck, Servier, Amgen Sanofi, Novartis, Cytokinetics, American Regent, and Applied Therapeutics. Dr Hernandez has received research grants from Merck, AstraZeneca, Novartis, and Verily; and received honoraria from Merck, Bayer, Amgen, AstraZeneca, and Novartis. Dr Hilkert is an employee of Merck & Company, Inc. Dr Lam has received research grants from Bayer, the National Medical Research Council of Singapore, Boston Scientific, Roche Diagnostic, Medtronic, Vifor Pharma, and AstraZeneca; has received consulting fees from Merck, Bayer, Boston Scientific, Roche Diagnostic, Vifor Pharma, AstraZeneca, Novartis, Amgen, Janssen Research & Development LLC, Menarini, Boehringer Ingelheim, Abbott Diagnostics, Corvia, Stealth BioTherapeutics, Novo Nordisk, JanaCare, Biofourmis, Darma, Applied Therapeutics, MyoKardia, Cytokinetics, WebMD Global LLC, and Radcliffe Group Ltd, Corpus; has a patent pending (PCT/SG2016/050217 & 16/216929); and is a co-founder and nonexecutive director of eKo.ai. Dr O’Connor has received research funding from Merck and consulting fees from Bayer, Dey LP, and the Bristol Myers Squibb Foundation. Dr Pieske has received research support from Boston Scientific and honoraria from Bayer, MSD, Novartis, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, BMS, Edwards Lifesciences, and Boston Scientific. Dr Ponikowski has received research grants, consulting fees, and Speakers Bureau for Bayer, MSD, Servier, Novartis, Vifor Pharma Ltd, BMS, Boehringer Ingelheim, Respicardia, AstraZeneca, Cibiem, RenalGuard Solutions, and Berlin-Chemie. Dr Roessig is an employee of Bayer AG. Dr Voors has received research support and honoraria from AstraZeneca, BMS, Bayer, Boehringer Ingelheim, Cytokinetics, Merck, Novartis, Novo Nordisk, and Roche Diagnostics. Dr Anstrom has received research grants from Merck and the National Institutes of Health. Dr Armstrong has received research grants from Merck, Bayer, Sanofi-Aventis Recherche & Développement, Boehringer Ingelheim, and CSL Limited; and has received consulting fees from Merck, Bayer, AstraZeneca, and Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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23. The association between social determinants of health and patient-centred outcomes in adults with heart failure with reduced ejection fraction.
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Dunbar SB, Tan X, Lautsch D, Maculaitis MC, Ricker B, Nagle T, Clark LT, Hilkert R, Brady JE, Black HL, and Spertus JA
- Subjects
- Aged, Humans, Adult, Female, United States, Cross-Sectional Studies, Stroke Volume, Medicare, Chronic Disease, Social Determinants of Health, Heart Failure therapy
- Abstract
Aims: To explore the associations between social determinants of health and patient-centred outcomes among adults with chronic heart failure with reduced ejection fraction., Design: Cross-sectional online self-report survey., Methods: A survey assessing social determinants of health (demographics, socio-economic position, affordability of care and social support) and patient-centred outcomes, including the Kansas City Cardiomyopathy Questionnaire-12 and validated measures of medication adherence, treatment satisfaction, treatment burden and mental health, was completed by 512 adults with chronic heart failure with a reduced ejection fraction between 06 March and 29 June 2020. Multivariable analyses included linear and logistic regression., Results: Female gender, having a care partner, and being offered financial assistance with medications were associated with worse health status, while perceiving medication as affordable and being married were associated with better health status. Females and having Medicaid, dual Medicaid/Medicare or no medical insurance were associated with a higher likelihood of depression, and non-white race/ethnicity was associated with less depression. Medication adherence was lower in patients having a care partner and offered financial assistance. Patients being offered financial and medication management assistance were more likely to be overwhelmed by the treatment burden, whereas those having some college education were less so., Conclusions: Social determinants of health are associated with patients' disease-specific health status, mental health and treatment satisfaction and burden. These findings underscore the importance of assessing social determinants of health in clinical practice and the need for developing and testing novel strategies to determine whether they improve patients' health., Impact: The relationship between social determinants of health- and patient-centred outcomes was assessed; affordability of care and social support factors were most strongly associated with outcomes for patients with chronic heart failure and reduced ejection fraction, underscoring the importance of assessing social determinants of health in routine clinical care., Implications for the Profession And/or Patient Care: Social determinants of health data could potentially inform care delivery for patients with heart failure and reduced ejection fraction by helping to identify those who require additional support to manage their symptoms, access care and adhere to treatment. Social support and affordability of treatment were associated with most patient-centred outcomes, suggesting these factors may provide clinicians with an indicator of a patient's level of general well-being that could be assessed during routine follow-up care., Reporting Method: This research followed the STROBE checklist for cross-sectional studies., Patient or Public Contribution: Adults who have heart failure with reduced ejection fraction that consented to participate in the study provided the data used for all analyses reported on in the manuscript. Service users, caregivers or members of the public had no involvement in the study., (© 2023 John Wiley & Sons Ltd.)
- Published
- 2023
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24. Applicability of Vericiguat to Patients Hospitalized for Heart Failure in the United States.
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Khan MS, Xu H, Fonarow GC, Lautsch D, Hilkert R, Allen LA, DeVore AD, Alhanti B, Yancy CW, Albert NM, Butler J, and Greene SJ
- Subjects
- Aged, Humans, Female, United States epidemiology, Aftercare, Medicare, Patient Discharge, Stroke Volume, Heart Failure therapy
- Abstract
Background: In January 2021, vericiguat, a soluble guanylate cyclase stimulator, was approved by the U.S. Food and Drug Administration (FDA) to reduce the risk of cardiovascular death and heart failure (HF) hospitalization among patients with a recent worsening HF event based on the VICTORIA (VerICiguaT Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial., Objectives: This study sought to leverage a contemporary U.S. registry of patients hospitalized for heart failure (HF) to characterize patients who may be candidates for vericiguat based on FDA label and the VICTORIA trial eligibility criteria., Methods: The authors studied patients hospitalized for HF with ejection fraction (EF) <45% across 525 sites in the GWTG-HF (Get With The Guidelines-Heart Failure) registry between January 2014 and December 2020. Approximate FDA label criteria (excluding estimated glomerular filtration rate [eGFR] <15 mL/min/1.73 m
2 , dialysis, or patients with heart transplantation or durable mechanical circulatory support) and eligibility criteria for the VICTORIA trial were applied to the GWTG-HF cohort., Results: Among 241,057 patients with EF <45% in the GWTG-HF registry, 221,730 (92%) could be candidates for vericiguat under the FDA label and 92,249 (38%) would have been eligible for the VICTORIA trial. The most frequent reasons for ineligibility for the FDA label were eGFR <15 mL/min/1.73 m2 (5.7%) and dialysis (1.6%). Although there were greater proportions of women and Black patients in the GWTG-HF registry, most clinical characteristics were qualitatively similar with patients enrolled in the VICTORIA trial. Among Medicare beneficiaries in the GWTG-HF registry eligible for vericiguat by either FDA label or VICTORIA trial criteria, 12-month postdischarge rates of mortality (36%-37%), HF hospitalization (33%-35%), all-cause hospitalization (64%-66%), and mean health care expenditure (U.S. $25,106-$25,428) were high., Conclusions: Data from a large, contemporary U.S. registry of patients actively hospitalized for HF with EF <45% suggest that approximately 4 in 10 patients meet the criteria of the VICTORIA trial and that more than 9 in 10 patients are potential candidates for vericiguat based on the FDA label. Contemporary Medicare beneficiaries hospitalized for HF with EF <45% and eligible for vericiguat face high rates of postdischarge mortality and readmission and accrue substantial health care costs., Competing Interests: Funding Support and Author Disclosures This study was supported by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc (Rahway, New Jersey, USA). The Get With The Guidelines–Heart Failure program is provided by the American Heart Association and sponsored, in part, by Novartis, Boehringer Ingelheim and Eli Lilly Diabetes Alliance, Novo Nordisk, Sanofi, AstraZeneca, and Bayer. Dr Fonarow has served as a consultant for Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Janssen, Medtronic, Merck Sharp & Dohme LLC (a subsidiary of Merck & Co, Inc), and Novartis. Drs Lautsch and Hilkert are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc. Dr Allen has received grant support from the National Institutes of Health and Patient-Centered Outcomes Research Institute; and has received consulting fees from ACI Clinical, American Heart Association, Boston Scientific, Cytokinetics, Novartis, and UpToDate. Dr Albert has received grant support from Novartis and AstraZeneca; and consulting fees from Boston Scientific, Boehringer Ingelheim/Lilly, Cytokinetics, and Merck Sharp & Dohme LLC (a subsidiary of Merck & Co, Inc). Dr Butler has served as a consultant for Abbott, Adrenomed, Arena Pharma, Array, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Cardior, CVRx, Eli Lilly, G3 Pharma, Imbria, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck Sharp & Dohme LLC (a subsidiary of Merck & Co, Inc), Novartis, Novo Nordisk, Sequana Medical, V-Wave Limited, and Vifor. Dr Greene has received research support from the Duke University Department of Medicine Chair’s Research Award, American Heart Association (#929502), National Heart, Lung, and Blood Institute, Amgen, AstraZeneca, Bristol Myers Squibb, Cytokinetics, Merck Sharp & Dohme LLC (a subsidiary of Merck & Co, Inc), Novartis, Pfizer, and Sanofi; served on the advisory board for Amgen, AstraZeneca, Boehringer Ingelheim/Lilly, Bristol Myers Squibb, Cytokinetics, Roche Diagnostics, scPharmaceuticals, and Sanofi; and served as a consultant for Amgen, Bayer, Boehringer Ingelheim/Lilly, Bristol Myers Squibb, CSL Vifor, Corteria Therapeutics, Merck Sharp & Dohme LLC (a subsidiary of Merck & Co, Inc), PharmaIN, Roche Diagnostics, Sanofi, Tricog Health, and Urovant Pharmaceuticals; and has received speaker fees from Boehringer Ingelheim and Cytokinetics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)- Published
- 2023
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25. Outpatient versus inpatient intravenous diuretic therapy for heart failure in the United States.
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Greene SJ, Goto D, Wang D, Hilkert R, Lautsch D, and Fonarow GC
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- United States epidemiology, Humans, Outpatients, Inpatients, Administration, Intravenous, Diuretics therapeutic use, Heart Failure drug therapy
- Published
- 2022
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26. Medication Trajectory and Treatment Patterns in Medicare Patients With Heart Failure and Reduced Ejection Fraction.
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Mentz RJ, Lautsch D, Pulungan Z, Kim S, Hilkert R, Teigland C, Yang M, and Djatche L
- Subjects
- Adrenergic beta-Antagonists therapeutic use, Aged, Angiotensin Receptor Antagonists pharmacology, Angiotensin Receptor Antagonists therapeutic use, Humans, Medicare, Mineralocorticoid Receptor Antagonists therapeutic use, Neprilysin, Retrospective Studies, Stroke Volume, United States epidemiology, Heart Failure drug therapy, Heart Failure epidemiology
- Abstract
Background: Although a worsening heart failure event (WHFE) is associated with poor outcomes in patients with heart failure with reduced ejection fraction (HFrEF), it is unclear how guideline-directed medical therapy (GDMT) is used in this population compared to those without WHFEs. This study evaluated treatment patterns in patients with HFrEF, both with and without WHFEs., Methods: A retrospective study using 100% Medicare Fee-For-Service claims identified beneficiaries with HFrEF, stratified by those with and without WHFEs (defined as hospitalization due to HF or outpatient intravenous diuretic use). The use of GDMT for HFrEF before and after WHFEs and adherence were assessed in patients who were prescribed and initiated GDMT. Logistic regression identified patients' characteristics associated with medication nonadherence., Results: Of 353,642 patients with HFrEF, 31.4% had a WHFE. Although there was no overall change in the treatment trajectory of patients without WHFEs, GDMT use in patients with WHFEs intensified within the first 3 months of a WHFE, but the intensification was not sustained in subsequent months. From 0-3 months pre-WHFE to 0-3 months post-WHFE, the proportion of patients receiving dual (41%-48%) and triple-therapy (4%-12%) increased, followed by a decline to pre-WHFE rates. The 1-year adherence rates for those with and without WHFEs were 67.9% vs 73.3% for beta-blockers; 59.1% vs 70.9% for angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists; 53.9% vs 61.3% for angiotensin receptor-neprilysin inhibitors; and 49.2% vs 59.3% for mineralocorticoid receptor antagonists. WHFE, age < 65 years, Black race, asthma, chronic kidney disease, and depression were associated with nonadherence to medications. Asians and Hispanics were less adherent to some medication classes., Conclusions: This study demonstrated underuse of GDMT for patients with HFrEF with or without WHFEs. Although there was a treatment escalation within 3 months following WHFE, it was not sustained thereafter., (Copyright © 2021 Merck Sharp & Dohme Corp., The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2022
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27. Out-of-pocket payments for part d covered medications by medicare fee-for-service beneficiaries with heart failure with reduced ejection fraction.
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Fendrick AM, Djatche L, Pulungan Z, Teigland C, Yang M, Lautsch D, Hilkert R, and Mentz R
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- Aged, Fee-for-Service Plans, Health Expenditures, Humans, Stroke Volume, United States, Heart Failure drug therapy, Medicare Part D
- Abstract
Background: Out-of-pocket (OOP) drug costs for Medicare Fee-for-Service (FFS) beneficiaries with heart failure with reduced ejection fraction (HFrEF) are not well characterized. This study evaluated Part D OOP spending by Medicare beneficiaries with chronic HFrEF, stratified by those with and without a worsening HF event (WHFE)., Methods: Medicare FFS 100% Part D claims were used to identify HFrEF patients with 12 months of continuous Part D enrollment in 2018. HFrEF was defined as 1 inpatient or 2 outpatient claims of systolic HF or 1 systolic HF plus 1 HF outpatient claim. WHFE was defined as having a HF hospitalization or intravenous diuretic use within 12 months of HFrEF index date. OOP costs by Medicare Part D coverage phase for all covered drugs were calculated for HFrEF patients, and those with and without WHFE., Results: Of 305,373 Medicare patients with HFrEF, 26% had a WHFE. Total mean (SD) OOP drug costs among all HFrEF patients was $1,166 (1,205)/year. Patients with WHFE and patients without WHFE had respectively a mean (SD) annual OOP costs of $1,302 (1,273) and $1,117 (1,176). Over 39% of HFrEF patients entered the "donut hole" (44% and 37% of patients with WHFE and without WHFE, respectively), while 11% of HFrEF patients entered the catastrophic phase (13% and 10% of patients with and without WHFE, respectively)., Conclusions: More than 1 in 10 patients with heart failure entered the catastrophic phase within Medicare-Fee-For-Service, whereas in 2018 only 10% of costs were attributable to heart failure medication and 90% to comorbidities., (Copyright © 2021 Merck Sharp & Dohme Corp,, The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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28. Patient-centered Outcomes in HFrEF Following a Worsening Heart Failure Event: A Survey Analysis.
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Dunbar SB, Tan X, Lautsch D, Yang M, Ricker B, Maculaitis MC, Nagle T, Clark LT, Hilkert R, Brady JE, and Spertus JA
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- Hospitalization, Humans, Patient-Centered Care, Stroke Volume, Surveys and Questionnaires, Heart Failure drug therapy, Heart Failure epidemiology
- Abstract
Background: Heart failure is a chronic disease punctuated by intermittent exacerbations that require hospitalization or intravenous diuretic therapy. The association of worsening heart failure events (WHFEs) with patient-centered outcomes in heart failure with reduced ejection fraction (HFrEF) remains unexplored., Methods and Results: Patients with HFrEF completed an online survey assessing health status, medication adherence, treatment satisfaction, treatment burden, and medication costs and affordability. Patients with and without WHFEs were compared on all study variables, with adjustment for patient characteristics using linear or logistic regression. Overall, 512 patients (52.0% WHFEs) were included. Patients with WHFEs more commonly had depression (55.3% vs 24.0%), anxiety (46.2% vs 17.9%), and insomnia (77.8% vs 44.7%; P < 0.001 for all). Patients with WHFEs had lower adjusted mean Kansas City Cardiomyopathy Questionnaire values (52.9 vs 56.0) and Satisfaction with Medications Questionnaire values (70.5 vs 72.6) and higher Treatment Burden Questionnaire scores (51.1 vs 45.1; P < 0.001). Medication-related beliefs and long-term concerns were independently associated with nonadherence in patients with WHFE (adjusted odds ratios: 4.2 and 5.2, respectively; P < 0.01 for both). Patients with WHFE incurred 50.0% higher median monthly out-of-pocket HF prescription medication costs and less often perceived HF medications to be affordable., Conclusions: WHFE is associated with several adverse impacts on patients with HFrEF. Additional support is warranted to manage symptoms, comorbidities, and HF treatments to improve adherence and outcomes., Competing Interests: Declaration of Competing Interest SBD has received consultation fees from Merck & Co. XT, DL, LTC, RH, and JEB are employees of Merck Sharp & Dohme, a subsidiary of Merck & Co., Kenilworth, NJ, and are stockholders in Merck & Co., Kenilworth, NJ. MY was an employee of Merck Sharp & Dohme, a subsidiary of Merck during the time of conducting this study; BR, MCM and TN are employees of Kantar, which received funding from Merck & Co. to conduct and report on the study; JAS has served as a consultant on the use of PROs to Merck, Bayer, Amgen, Myokardia, Novartis, and Janssen; he owns the copyright to the Kansas City Cardiomyopathy, Seattle Angina and Peripheral Artery questionnaires and has an equity interest in Health Outcomes Sciences; he serves on a cardiovascular advisory board for United Healthcare and the Board of Directors for Blue Cross Blue Shield of Kansas City., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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29. Quality outcomes, healthcare resource utilization and costs in Medicare patients with chronic heart failure with reduced ejection fraction with and without a worsening event.
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Mentz RJ, Pulungan Z, Kim S, Yang M, Teigland C, Hilkert R, and Djatche LM
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- Aged, Fee-for-Service Plans, Humans, Patient Acceptance of Health Care, Retrospective Studies, Stroke Volume, United States, Heart Failure, Medicare Part C
- Abstract
Aims: The study compared quality outcomes, resource utilization, and costs in Medicare beneficiaries with chronic heart failure with reduced ejection fraction (HFrEF) with and without a worsening heart failure event (WHFE)., Methods: This retrospective observational study evaluated claims data for two cohorts of Medicare beneficiaries with chronic HFrEF who were enrolled in Medicare fee-for-service (FFS) or Medicare advantage (MA) plans. The index date was the first claim of HFrEF between October 2015 and September 2017. Patients with WHFE were identified if they had IV diuretic use or hospitalization for HF during 12 months after index date; with remaining patients classified as non-WHFE. During follow-up, starting from the 13
th month after HFrEF index date to end of follow-up, generalized linear models were used to adjust for patient characteristics to compare mean per patient per year (PPPY) quality outcomes, resource utilization, and costs between HFrEF patients with and without WHFE., Results: Of the 1,182,509 FFS and 28,645 MA patients with HFrEF, 34.2% and 32.5% developed WHFE, respectively. Compared to patients without WHFE, patients with WHFE had higher rates of all-cause 30-day readmissions (FFS: 42% vs. 31%; MA: 41% vs. 31%), hospitalizations (FFS: 2.27 vs. 1.36; MA: 1.47 vs. 0.78 PPPY) and ED visits (FFS: 1.82 vs. 1.25; MA: 1.43 vs. 0.96 PPPY); all comparisons p < .05. Mortality rates in FFS patients were higher among patients with WHFE (34.3%) compared to those without (23.4%). All-cause total PPPY costs were higher for patients with WHFE compared to those without by $20,825 in FFS and $15,974 in MA. Similar trends were observed for HF-related outcomes., Conclusion: Medicare patients with chronic HFrEF experiencing a WHFE had worse quality outcomes as well as higher resource utilization and costs compared to those without WHFE, thus, suggesting the need for better treatments and interventions to manage these patients.- Published
- 2021
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30. Comparative efficacy and safety of combination aliskiren/amlodipine and amlodipine monotherapy in African Americans with stage 2 hypertension.
- Author
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Black HR, Weinberger MH, Purkayastha D, Lee J, Sridharan K, Israel M, Hilkert R, and Izzo J
- Subjects
- Adult, Amides adverse effects, Amides pharmacology, Amlodipine adverse effects, Amlodipine pharmacology, Blood Pressure drug effects, Blood Pressure physiology, Blood Pressure Monitoring, Ambulatory, Double-Blind Method, Drug Therapy, Combination, Edema chemically induced, Edema epidemiology, Fatigue chemically induced, Fatigue epidemiology, Female, Fumarates adverse effects, Fumarates pharmacology, Headache chemically induced, Headache epidemiology, Humans, Hypertension physiopathology, Incidence, Male, Middle Aged, Prospective Studies, Treatment Outcome, Black or African American ethnology, Amides therapeutic use, Amlodipine therapeutic use, Fumarates therapeutic use, Hypertension drug therapy, Hypertension ethnology, Severity of Illness Index
- Abstract
Initial multiple drug therapy for hypertension achieves greater and quicker reductions and higher blood pressure (BP) control rates than monotherapy. This 8-week, prospective, multicenter, randomized, double-blind study compared the efficacy and safety of the initial combination of aliskiren/amlodipine with amlodipine monotherapy in African Americans with stage 2 hypertension. After a 1- to 4-week washout, patients received aliskiren/amlodipine 150/5 mg or amlodipine 5 mg for 1 week and then were force-titrated to aliskiren/amlodipine 300/10 mg or amlodipine 10 mg for 7 weeks. At week 8, greater reductions in mean sitting systolic BP were obtained with aliskiren/amlodipine (n = 220) than with amlodipine (n = 223) (least squares mean change [standard error of the mean], -34.1 [1.14] mm Hg vs -28.9 [1.12] mm Hg; P<.001). Ambulatory and central BP measures were consistent with clinic BP findings, although these were conducted in a small subset of patients (n = 94 in ambulatory BP monitoring substudy and n = 136 for central BP). More patients achieved goal BP (<140/90 mm Hg) with aliskiren/amlodipine than with amlodipine at week 8 (57.3% vs 48.0%; P = .051). Both treatment groups had similar adverse event rates (35.0% and 32.7%, respectively). The most common adverse events were peripheral edema (7.7% with aliskiren/amlodipine and 9.0% with amlodipine), headache, fatigue, and nausea. The combination of aliskiren/amlodipine reduced peripheral, ambulatory, and central BP more than amlodipine alone with similar tolerability in African Americans with stage 2 hypertension., (© 2011 Wiley Periodicals, Inc.)
- Published
- 2011
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31. Moderate versus intensive treatment of hypertension using amlodipine/valsartan and with the addition of hydrochlorothiazide for patients uncontrolled on angiotensin receptor blocker monotherapy: results in racial/ethnic subgroups.
- Author
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Ofili EO, Oparil S, Giles T, Pitt B, Purkayastha D, Hilkert R, Samuel R, and Sowers JR
- Subjects
- Adult, Black or African American, Aged, Blood Pressure drug effects, Double-Blind Method, Drug Therapy, Combination, Female, Hispanic or Latino, Humans, Male, Middle Aged, Valine administration & dosage, Valsartan, White People, Amlodipine administration & dosage, Antihypertensive Agents administration & dosage, Hydrochlorothiazide administration & dosage, Hypertension drug therapy, Hypertension ethnology, Receptors, Angiotensin administration & dosage, Tetrazoles administration & dosage, Valine analogs & derivatives
- Abstract
Combination therapy may reduce racial/ethnic differences in response to antihypertensives. In this post-hoc analysis, we evaluated treatment response by race/ethnicity among hypertensive adults enrolled in a 12-week, double-blind study in which patients previously uncontrolled (mean sitting systolic blood pressure [MSSBP] ≥150 and <200 mm Hg) on angiotensin receptor blocker (ARB) monotherapy (other than valsartan) for 28 days or more (n = 728) were randomized to amlodipine/valsartan 10/320 mg (intensive) or 5/160 mg (moderate). Treatment-naïve patients (in previous 28 days) or those who failed on a non-ARB first underwent a 28-day run-in period with olmesartan 20 mg or 40 mg, respectively. Hydrochlorothiazide (HCTZ) 12.5 mg was added to both arms at week 4; optional up-titration to 25 mg at week 8 (if MSSBP >140 mm Hg). Intensive treatment provided greater BP lowering versus moderate treatment throughout the study, regardless of race/ethnicity (474 white, 198 African American, 165 Hispanic individuals). Least-square mean reductions from baseline to week 4 in MSSBP (primary outcome) ranged from 20.4 to 23.5 mm Hg (intensive) versus 17.5 to 19.0 mm Hg (moderate), across racial/ethnic subgroups. Both regimens were well tolerated. Amlodipine/valsartan/HCTZ combination therapy was efficacious across racial/ethnic subgroups. Maximal efficacy was obtained with intensive treatment., (Copyright © 2011. Published by Elsevier Inc.)
- Published
- 2011
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32. The role of ambulatory blood pressure monitoring compared with clinic and home blood pressure measures in evaluating moderate versus intensive treatment of hypertension with amlodipine/valsartan for patients uncontrolled on angiotensin receptor blocker monotherapy.
- Author
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Giles TD, Oparil S, Ofili EO, Pitt B, Purkayastha D, Hilkert R, Samuel R, and Sowers JR
- Subjects
- Adult, Aged, Amlodipine, Valsartan Drug Combination, Blood Pressure drug effects, Blood Pressure Monitoring, Ambulatory instrumentation, Double-Blind Method, Drug Combinations, Female, Humans, Male, Middle Aged, Self Care instrumentation, Self Care methods, Amlodipine therapeutic use, Angiotensin Receptor Antagonists therapeutic use, Antihypertensive Agents therapeutic use, Blood Pressure Monitoring, Ambulatory methods, Hypertension drug therapy, Tetrazoles therapeutic use
- Abstract
Objectives: Ambulatory blood pressure monitoring (ABPM) has greater predictive value than office blood pressure (BP) with respect to hypertension-related target-organ damage and morbidity. ABPM in a subset of 80 patients from the Exforge Target Achievement trial (N=728) was used to compare the efficacy of intensive-treatment and moderate-treatment regimens of amlodipine/valsartan, and to determine whether treatment differences could be better assessed with ABPM than with office or home BP. Home BP was measured on the morning of clinic visits to minimize differences that timing might have on home versus office BP measures., Methods: A 12-week randomized, double-blind study in which hypertensive patients earlier uncontrolled (mean sitting systolic BP≥150 and <200 mmHg) on angiotensin receptor blocker monotherapy (other than valsartan) after 28 days or more (N=728) were randomized to amlodipine/valsartan treatment [10/320 mg (intensive) or 5/160 mg (moderate)]. Treatment-naive patients (in previous 28 days) or patients who failed on a nonangiotensin receptor blocker agent underwent a 28-day run-in period with a 20-mg or 40-mg dose of olmesartan, respectively., Results: Significantly greater 24-h ABP reductions from baseline to week 4 (primary time point) were observed with intensive versus moderate treatment (least-square mean systolic/diastolic BP reduction of -16.2/-10.1 vs. -9.5/-6.5 mmHg; P=0.0024/P=0.010 for least-square mean difference). Similarly, a significantly greater proportion of patients receiving an intensive treatment achieved ambulatory BP goal (<130/80 mmHg) at week 4 than did those receiving a moderate treatment (P=0.040). Treatment-group differences did not reach statistical significance for these end points when measured by office and home BP., Conclusion: In this first randomized trial evaluating the effects of intensive versus moderate dosing of the combination of amlodipine/valsartan, our data suggest that ABPM was a better method for assessing between-treatment differences than clinic or home BP recordings, although measurement of home BP as a single recording was a limitation of our trial.
- Published
- 2011
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33. EXCEED: Exforge-intensive control of hypertension to evaluate efficacy in diastolic dysfunction: study rationale, design, and participant characteristics.
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Hassanein A, Desai A, Verma A, Oparil S, Izzo J, Rocha R, Hilkert R, Seifu Y, Pitt B, and Solomon S
- Subjects
- Aged, Amlodipine therapeutic use, Amlodipine, Valsartan Drug Combination, Diastole, Drug Combinations, Echocardiography, Doppler methods, Female, Humans, Hypertension complications, Hypertension physiopathology, Hypertrophy, Left Ventricular complications, Male, Manometry, Middle Aged, Prospective Studies, Radial Artery, Severity of Illness Index, Tetrazoles therapeutic use, Antihypertensive Agents therapeutic use, Blood Pressure drug effects, Hypertension drug therapy
- Abstract
Background: Both diastolic dysfunction and increased vascular stiffness represent important measures of target-organ damage in hypertension. Whether intensive blood pressure (BP) control can further improve these measures remains unknown., Methods: EXCEED is a prospective, randomized open-label blinded endpoint trial (PROBE) design, aiming to test the hypothesis that more aggressive BP lowering would result in greater improvement in diastolic function among patients with stage II hypertension, evidence of diastolic dysfunction and preserved systolic function (EF > or = 50%). Patients were randomized to one of two treatment strategies, targeting systolic blood pressure (SBP) <140 mmHg or <130 mmHg using a combination of amlodipine/valsartan with additional antihypertensive medications as needed to achieve the prescribed targets. Diastolic function was assessed using Doppler tissue imaging of early diastolic velocity of lateral mitral annulus (E'), while vascular stiffness was assessed using radial augmentation index (RAI) derived from radial artery tonometry. The study primary endpoint will be the change in lateral E' velocity between baseline and 24 weeks., Results: Two hundred and twenty eight patients (50% female) with mean age of (59.6+/-9.7) years and mean BP of (162+/-14/92+/-13 mmHg) were randomized equally to either treatment strategies. Left ventricular hypertrophy was present among <4% of the enrolled patients. Inspite diastolic function was impaired, baseline lateral E' velocity (7.6+/-1.2 cm/s) was not related to baseline SBP while baseline RAI was weakly related (r = 0.2, p <0.01) to SBP even after adjustment to age, gender and heart rate., Conclusion: EXCEED will determine whether intensive BP lowering will further improve diastolic dysfunction and vascular stiffness among patients with uncontrolled hypertension.
- Published
- 2009
- Full Text
- View/download PDF
34. Magnetic resonance imaging left ventricular mass reduction with fixed-dose angiotensin-converting enzyme inhibitor-based regimens in patients with high-risk hypertension.
- Author
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Reichek N, Devereux RB, Rocha RA, Hilkert R, Hall D, Purkayastha D, and Pitt B
- Subjects
- Aged, Amlodipine adverse effects, Amlodipine pharmacology, Amlodipine therapeutic use, Angiotensin-Converting Enzyme Inhibitors adverse effects, Benzazepines adverse effects, Benzazepines pharmacology, Benzazepines therapeutic use, Calcium Channel Blockers adverse effects, Calcium Channel Blockers pharmacology, Calcium Channel Blockers therapeutic use, Diuretics adverse effects, Diuretics pharmacology, Diuretics therapeutic use, Dose-Response Relationship, Drug, Double-Blind Method, Drug Combinations, Female, Humans, Hydrochlorothiazide adverse effects, Hydrochlorothiazide pharmacology, Hydrochlorothiazide therapeutic use, Hypertrophy, Left Ventricular pathology, Magnetic Resonance Imaging, Male, Middle Aged, Risk Factors, Sex Characteristics, Treatment Outcome, Angiotensin-Converting Enzyme Inhibitors pharmacology, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Heart Ventricles drug effects, Heart Ventricles pathology, Hypertension complications, Hypertension drug therapy, Hypertrophy, Left Ventricular epidemiology
- Abstract
Left ventricular hypertrophy, a major cardiovascular risk factor for morbidity and mortality, is commonly caused by arterial hypertension. The renin-angiotensin-aldosterone system may contribute to the pathogenesis of left ventricular hypertrophy. The Assessment of Lotrel in Left Ventricular Hypertrophy and Hypertension Study compared a single-pill combination of amlodipine/benazepril at doses 5.0/20.0 mg, 5.0/40.0 mg, and 10.0/40.0 mg with hydrochlorothiazide/benazepril at doses 12.5/20.0 mg, 12.5/40.0 mg, and 25.0/40.0 mg on the reduction of left ventricular mass index measured by cardiac MRI in stage 2 hypertensive patients over 52 weeks of treatment in a randomized clinical trial. A total of 125 male and female patients, > or =55 years of age, with echocardiographic left ventricular hypertrophy and high-risk hypertension defined as blood pressure > or =160/100 mm Hg or current antihypertensive treatment were enrolled. After 52 weeks of treatment, left ventricular mass index was significantly reduced from baseline with amlodipine/benazepril (mean: 10.16 g/m(2)) or hydrochlorothiazide/benazepril (mean: 6.74 g/m(2); both P<0.0001), with a mean difference between treatment groups of 3.36 g/m(2) (P=0.16). No significant treatment differences were observed in subgroups defined by age, male gender, race, diabetes status, or dose level. However, in female patients, left ventricular mass index reduction was greater with amlodipine/benazepril (P=0.02). Both treatments were well tolerated.
- Published
- 2009
- Full Text
- View/download PDF
35. Single-pill combination of amlodipine and valsartan in the management of hypertension.
- Author
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Flack JM and Hilkert R
- Subjects
- Amlodipine pharmacokinetics, Amlodipine pharmacology, Angiotensin II Type 1 Receptor Blockers pharmacokinetics, Angiotensin II Type 1 Receptor Blockers pharmacology, Antihypertensive Agents pharmacokinetics, Antihypertensive Agents pharmacology, Blood Pressure drug effects, Calcium Channel Blockers pharmacokinetics, Calcium Channel Blockers pharmacology, Drug Combinations, Humans, Patient Compliance, Tetrazoles pharmacokinetics, Tetrazoles pharmacology, Valine pharmacokinetics, Valine pharmacology, Valine therapeutic use, Valsartan, Amlodipine therapeutic use, Angiotensin II Type 1 Receptor Blockers therapeutic use, Antihypertensive Agents therapeutic use, Calcium Channel Blockers therapeutic use, Hypertension drug therapy, Tetrazoles therapeutic use, Valine analogs & derivatives
- Abstract
Combination therapy is increasingly recommended for selected patients with hypertension to facilitate prompt attainment and maintenance of goal blood pressure (BP). Single-pill combination therapy simplifies treatment and optimizes long-term compliance. Amlodipine, a dihydropyridine calcium antagonist, and valsartan, an angiotensin receptor blocker, are well-established antihypertensive agents with complementary mechanisms of action. This combination lowers BP significantly more than either of its components, and valsartan reduces the incidence of dose-related amlodipine-induced edema. Rigorous clinical trial data have proven the BP-lowering efficacy and high tolerability of the amlodipine/valsartan combination in patients with moderate to severe hypertension as well as other difficult-to-treat populations. Amlodipine/valsartan is indicated as initial therapy in patients who are unlikely to be controlled with a single drug and as second-line therapy in patients not responding adequately to monotherapy.
- Published
- 2009
- Full Text
- View/download PDF
36. Sleep and quality of life in stable heart failure.
- Author
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Redeker NS and Hilkert R
- Subjects
- Adult, Aged, Aged, 80 and over, Cross-Sectional Studies, Female, Heart Failure complications, Humans, Male, Middle Aged, Sleep Wake Disorders etiology, Surveys and Questionnaires, Heart Failure physiopathology, Heart Failure psychology, Quality of Life, Sleep Wake Disorders physiopathology
- Abstract
Background: Functional performance and mental health are significant quality of life concerns for heart failure (HF) patients. Poor sleep also appears to be common. We examined the extent to which sleep was associated with functional performance and mental health among persons who had stable systolic HF., Methods and Results: Sixty-one patients with stable systolic HF wore wrist actigraphs to record nocturnal sleep and daily activity for 3 days while living at home, performed 6-minute walks (6MWT), and completed the Pittsburgh Sleep Quality Index and the Medical Outcomes Study SF-36 questionnaire. Self-reported sleep quality and actigraph-recorded wake time and wake bout time explained 9% to 20% of the variance in the functional performance variables (daytime activity level, 6MWT, self-reported physical function), and mental health, after controlling for age, gender, comorbidity, and New York Heart Association class. Time in bed was negatively associated with functional performance. There were no statistically significant relationships between sleep duration and functional performance., Conclusions: Self-reported sleep quality and sleep continuity (sleep that is undisturbed by nocturnal awakenings) are associated with functional performance and mental health in stable systolic HF patients. Effective treatment of sleep problems may contribute to improvement in quality of life.
- Published
- 2005
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37. Repair of left ventricular aneurysm: long-term results of linear repair versus endoaneurysmorrhaphy.
- Author
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Shapira OM, Davidoff R, Hilkert RJ, Aldea GS, Fitzgerald CA, and Shemin RJ
- Subjects
- Case-Control Studies, Female, Follow-Up Studies, Heart Aneurysm diagnostic imaging, Heart Aneurysm mortality, Heart Aneurysm physiopathology, Humans, Male, Middle Aged, Retrospective Studies, Survival Rate, Time Factors, Ultrasonography, Ventricular Function, Left physiology, Heart Aneurysm surgery
- Abstract
Background: Recently, endoaneurysomorrhaphy has been proposed as a more physiologic repair of postinfarction left ventricular aneurysm than is linear repair. There are only a few studies comparing the short-term and long-term results of the two techniques., Methods: Clinical outcomes and echocardiographic measurements of left ventricular volume and sphericity in 27 patients who underwent endoaneurysmorrhaphy were compared with those in 20 patients who had linear repair., Results: The two groups were matched with respect to age, gender, comorbid risk factors, functional class, urgency of the operation, and concomitant procedures. Preoperatively, left ventricular ejection fraction was lower in the endoaneurysmorrhaphy group (0.25 +/- 0.08 versus 0.30 +/- 0.09; p = 0.03). Follow-up was available in 44 patients (94%) and ranged from 2 to 86 months (mean, 41.0 +/- 26.5 months). Thirty-day operative mortality, perioperative complications, 5-year survival, and freedom from cardiac death were similar. Early postoperative percentage increase in left ventricular ejection fraction was greater after endoaneurysmorrhaphy (0.51 +/- 0.64 versus 0.18 +/- 0.48; p = 0.036). Long-term functional improvement was significantly better in the endoaneurysmorrhaphy group: At the time of last follow-up, 88% of patients were in New York Heart Association class I/II, compared with 53% after linear repair (p = 0.01). There were no measurable differences between the groups with respect to left ventricular ejection fraction (0.28 +/- 0.11 versus 0.27 +/- 0.11; p = 0.90), left ventricular volume (171.6 +/- 59.1 versus 169.9 +/- 54.4 mL; p = 0.94), and sphericity index (0.61 +/- 0.09 versus 0.61 +/- 0.12; p = 1.0)., Conclusions: Despite having a similar effect on left ventricular geometry, endoaneurysmorrhaphy resulted in a greater increase in postoperative left ventricular ejection fraction and a substantially improved long-term clinical outcome.
- Published
- 1997
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38. Left ventricular dysfunction during infrarenal abdominal aortic aneurysm repair.
- Author
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Gillespie DL, Connelly GP, Arkoff HM, Dempsey AL, Hilkert RJ, and Menzoian JO
- Subjects
- Aged, Aged, 80 and over, Aortic Aneurysm, Abdominal diagnosis, Arterial Occlusive Diseases etiology, Blood Volume physiology, Constriction, Echocardiography, Transesophageal, Female, Humans, Kidney, Male, Medical History Taking, Middle Aged, Monitoring, Intraoperative, Multivariate Analysis, Postoperative Complications etiology, Premedication, Preoperative Care, Pulmonary Wedge Pressure physiology, Aortic Aneurysm, Abdominal physiopathology, Aortic Aneurysm, Abdominal surgery, Arterial Occlusive Diseases physiopathology, Postoperative Complications physiopathology, Pulmonary Artery physiopathology, Ventricular Function, Left physiology
- Abstract
Background: Clinical observations suggest that pulmonary artery occlusion pressure (PAOP) underestimates the resuscitative volumes required prior to release of aortic cross-clamp., Methods: To investigate pressure-volume relationships associated with repair of abdominal aortic aneurysm (AAA), we simultaneously monitored PAOP by pulmonary artery catheter (PAC) and estimated left ventricular (LV) diastolic volume using two-dimensional transesophageal echocardiography (TEE) in 22 patients undergoing AAA repair. Data from PAC monitoring and TEE were collected before, during, and after aortic occlusion. TEE cross-sectional images were obtained at the mid-papillary level., Results: Overall, PAOP correlated with left ventricular end-diastolic area (LVEDA), but the correlation was not particularly strong (r = 0.37, P < 0.0001). Even within individual patients, LVEDA varied widely for a given PAOP. The strength of the correlation between PAOP and LVEDA also appeared to deteriorate during the course of surgery. The best correlation was seen prior to aortic cross-clamping (r = 0.50, P < 0.0001), but fell somewhat during aortic cross-clamping (r = 0.41, P < 0.0001), and even further after unclamping (r = 0.25, P = 0.005)., Conclusion: This study demonstrates a relatively weak correlation between PAOP and LVEDA using intraoperative TEE during AAA repair. Furthermore, the strength of the correlation worsened during surgery, particularly after unclamping. Although unclear at this time, this finding may be attributable to changes in LV compliance. We found TEE to be a valuable adjunct in guiding volume resuscitation of patients undergoing AAA repair.
- Published
- 1994
- Full Text
- View/download PDF
39. Structural organization and chromosomal assignment of the gene encoding the human heparin-binding epidermal growth factor-like growth factor/diphtheria toxin receptor.
- Author
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Fen Z, Dhadly MS, Yoshizumi M, Hilkert RJ, Quertermous T, Eddy RL, Shows TB, and Lee ME
- Subjects
- Amino Acid Sequence, Animals, Base Sequence, Cells, Cultured, Chloramphenicol O-Acetyltransferase genetics, Chromosome Mapping, Cloning, Molecular, Epidermal Growth Factor chemistry, Exons, Heparin-binding EGF-like Growth Factor, Humans, Hybrid Cells, Intercellular Signaling Peptides and Proteins, Mice, Molecular Sequence Data, Promoter Regions, Genetic, Receptors, Cholinergic chemistry, Recombinant Fusion Proteins, Transcription, Genetic, Transfection, Chromosomes, Human, Pair 5, Epidermal Growth Factor genetics, Receptors, Cell Surface, Receptors, Cholinergic genetics
- Abstract
Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a recently identified, potent smooth muscle cell mitogen of macrophage origin. It is expressed in a highly regulated fashion in vascular endothelial and smooth muscle cells, indicating a potentially important role for this gene in atherosclerosis. In addition, the HB-EGF precursor has recently been found to function as a receptor for diphtheria toxin. Using an HB-EGF cDNA probe, we cloned the human gene encoding HB-EGF. The HB-EGF gene contains six exons and five intervening sequences spanning 14 kb of DNA. By primer extension and S1 nuclease analysis, we located a major transcription start site (corresponding to an A residue) 14 bp beyond the 5' end of the HB-EGF cDNA. There were no TATAAA or CCAAT consensus sequences upstream of the transcription start site. The density of primer extension bands generated by RNA from endothelial cells treated with tumor necrosis factor-alpha (TNF-alpha) was 10 times higher than that of bands generated by the control, indicating that TNF-alpha increased the level of HB-EGF mRNA. Using transient reporter gene transfection experiments, we show that 2.0 kb of HB-EGF 5'-flanking sequence has promoter activity in bovine aortic endothelial cells. By analysis of DNA isolated from human-mouse somatic hybrid cell lines, we assign the HB-EGF gene to chromosome 5. By functional study, chromosome 5 has been associated with diphtheria toxin susceptibility.
- Published
- 1993
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40. Genetic regulation of endothelin-1 in vascular endothelial cells.
- Author
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Hilkert RJ, Lee ME, and Quertermous T
- Abstract
Endothelin-1 (ET-1) is a potent vasoconstrictor and smooth muscle cell mitogen synthesized and secreted by endothelial cells. This vasoactive peptide is genetically regulated by many of the cytokines, hormones, and physical forces that are involved in vascular disease processes. Transcriptional regulation of the ET-1 gene depends upon the cis-acting elements of the ET-1 promoter and their interaction with the protooncogene products Fos and Jun as well as other DNA-binding proteins., (Copyright © 1992. Published by Elsevier Inc.)
- Published
- 1992
- Full Text
- View/download PDF
41. Properties of immunoaffinity purified 106-kDa Ca2+ release channels from the skeletal sarcoplasmic reticulum.
- Author
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Hilkert R, Zaidi N, Shome K, Nigam M, Lagenaur C, and Salama G
- Subjects
- Animals, Antibodies physiology, Calcium Channels drug effects, Calcium Channels immunology, Chromatography, Affinity, Ion Channel Gating, Molecular Weight, Oxidation-Reduction, Rabbits, Sarcoplasmic Reticulum drug effects, Sulfhydryl Compounds, Calcium Channels chemistry, Sarcoplasmic Reticulum chemistry
- Abstract
The sulfhydryl-gated 106-kDa Ca(2+)-release channel (SG-106) was purified by biotin-avidin chromatography from skeletal sarcoplasmic reticulum (SR) vesicles and used as an antigen to raise polyclonal antibodies. Western blots showed that the antisera crossreacted with the antigenic SG-106 and not with SR Ca2+, Mg(2+)-ATPase or with junctional foot proteins (JFPs) (Zaidi et al., 1989, J. Biol. Chem. 264(36), 21, 725-21, 736; 21, 737-21, 747). Polyclonal antibody-affinity columns were used to selectively purify SG-106-kDa proteins which, upon incorporation in planar bilayers, revealed the presence of a cationic channels with properties similar to "native" Ca(2+)-release channels obtained through the fusion of SR vesicles with planar bilayers. In agreement with measurements of Ca2+ release from SR vesicles, sulfhydryl oxidizing and reducing agents (i.e., 2,2'-dithiodipyridine and dithiothreitol) respectively increased and decreased the open-time probability of 106-kDa Ca(2+)-release channels. In contrast with reports on JFPs, ryanodine at 0.5-1 nM increased the open-time probability and at 2-10 nM locked 106-kDa Ca(2+)-release channels in a closed state rather than an open subconductance state. The SG-106 was activated by millimolar ATP, inhibited by millimolar Mg2+, and blocked by micromolar ruthenium red. Adriamycin (2-10 microM) caused a transient activation of SG-106 Ca(2+)-release channels, followed by closure in about 5 min, and intermittent activation to a subconductance state. Polyclonal antibodies used to purify the SG-106 also activated the channel when added to the cis side but not the trans side of the bilayer. Thus, SG-106 channels possess features that are similar to "native" SR Ca(2+)-release channels, are immunologically distinct from JFPs, and interact in seconds with nanomolar ryanodine in planar bilayers.
- Published
- 1992
- Full Text
- View/download PDF
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