Format

Send to

Choose Destination
Circulation. 2015 Jan 6;131(1):54-61. doi: 10.1161/CIRCULATIONAHA.114.013748. Epub 2014 Nov 17.

Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure.

Collaborators (1129)

McMurray J, Packer M, Rouleau J, Solomon S, Swedberg K, Zile M, Solomon S, Desai A, Kaplan A, Brown N, Zuraw B, Dargie H, Foley R, Francis G, Komajda M, Pocock S, Martinez F, Albisu J, Alvarisqueta A, Amuchastegui M, Astesiano A, Avila E, Beloscar J, Berli M, Borrego C, Bustos B, Calella P, Carbajales J, Caruso G, Caruso O, Casabé H, Cimbaro Canella J, Colombo Berra F, Colque R, Costello R, Dran R, Ferre Pacora F, Gabito A, Glenny J, Guzman P, Ibañez J, Ingaramo R, Kotliar C, Leon de la Fuente R, Liberman A, Liniado G, Llanos J, Lobo Marquez L, Luquez H, Mackinnon I, Mallagray M, Martingano R, Mercado D, Moises Azize G, Parody L, Perez Rey R, Petenian E, Rodríguez M, Rojas C, Romano A, Salvatierra Ruiz A, Sanchez A, Sarjanovich R, Sarries A, Schiavi L, Sessa H, Soler J, Vico M, Zaidman C, Vanhaecke J, Decroly P, Dendale P, Ector B, Friart A, Heyse A, Missault L, Mulleners T, Smolders W, Vandekerckhove H, Vincent M, Weytjens C, Wollaert B, Ramires F, Andrade C, Bassan R, Borelli F, Botelho R, Braga J, Braile M, Costa C, Costa F, Duda N, Garcia M, Greco O, Hernandes M, Jaeger C, Koehler I, Luiz Rech R, Mesquita E, Moraes J Jr, Neto J, Neuenschwander F, Paiva M, Rassi S, Reis G, Rossi P, Rabelo A, Reis H, Saporito W, Simoes M, Souza W, Vilas Boas F, Katova T, Benov H, Boeva-Chompalova B, Chobanska P, Denchev S, Dimov B, Donova T, Georgiev P, Gotchev D, Goudev A, Gruev T, Hergeldjieva V, Lazov P, Manukov I, Marchev S, Mihov L, Milanova M, Mileva-Manolova A, Mincheva-Kabakchieva V, Parvanova Z, Pencheva G, Petranov S, Raev D, Ramshev K, Sirakova V, Staneva A, Tisheva-Gospodinova S, Todorov G, Tokmakova M, Tzekova M, Valchanova P, Yotov Y, Zhelev V, Arnold M, Bergeron S, Bourgeois R, Bourgeois S, Cha J, DeGrâce M, Delgado D, Deslongchamps F, Dion D, Giannetti N, Huynh T, Johnston J, Klinke P, Kornder J, Labonte R, Lauzon C, Lepage S, Mak S, Moe G, Murthy D, Pandey S, Parker J, Rajda M, Robinson S, Rupka D, Sabe-Affaki G, Sestier F, Sheppard R, Yao L, Albornoz F, Avendaño P, Cobos L, Escobar E, Fernandez M, Jalil J, Lanas F, Sepulveda P, Stockins B, Yovaniniz P, Huang J, Gui M, Hu HD, Ke YN, Li LG, Li XD, Li XL, Li WM, Liu SW, Liu XH, Ma GS, Sun NL, Xu G, Yang K, Yuan ZY, Zhang J, Zhao RP, Gomez E, Accini J, Almanzar A, Coronel J, Cotes C, Echeverria L, Manzur F, María E, Reynales H, Rodriguez M, Sotomayor A, Urina M, Velasquez J, Vélez S, Vesga B, Belohlavek J, Burianova H, Carda J, Cech V, Cepelak M, Hanustiakova A, Horny I, Kolar K, Krupicka J, Kvasnicka J, Lindovsky P, Lorenc Z, Malek F, Malik J, Mandovec A, Petrova I, Podzemska B, Povolny P, Radvan M, Richter M, Riha V, Sabl P, Slaby J, Svejda J, Telekes P, Ulman J, Vomacka Z, Zemek S, Lederballe O, Refsgaard J, Andersen H, Egstrup K, Elming H, Eske N, Gøtzsche O, Jensen J, Køber L, May O, Pedersen O, Rickers H, Steffensen F, González A, Paulino A, Martinez P, Duarte YC, Delgado C, Duarte Y, Hidalgo FL, Mariscal C, Marmol R, Rosenthal A, Kaasik A, Kaik J, Laane E, Peuhkurinen K, Jääskeläinen T, Kiilavuori K, Taurio J, Hagege AA, Alexeeva-Kovalchuk A, Bauer F, Berdague P, Berneau JB, Bouvier JM, Damien L, Damy T, Davy JM, Decoulx DE, EL-Mansour N, Etchecopar C, Galinier M, Gibelin P, Gosse P, Guetlin A, Labeque JN, Livarek B, Logeart D, Martelet M, Nazeyrollas P, Neuder Y, Nourredine M, Poulard JE, RaidRihani R, Sabatier R, Tran NT, Yannick N, Zannad F, Böhm M, Adelberger V, Al-Zoebi A, Bastian A, Behrens S, Bessler H, Braun R, Brehm B, Buhr M, Cieslinski G, Dahl Jv, Daut W, Demmig HJ, Denny S, Ebert HH, Fechtrup C, Fischer S, Frick HM, Genth-Zotz S, Gerbaulet U, Germann H, Geßner S, Gola G, Grönefeld G, Hagenow A, Hampf J, Hartmann A, Hauf G, Hegeler-Molkewehrum C, Hegemann P, Hermes S, Himpel-Bönninghoff A, Hoeltz S, Jerwan-Keim R, Kadel C, Karle C, Kindermann I, Knapp M, Krause KH, Krosse B, Kühne U, Kuhrs M, Leicht M, Löbe M, Loos H, Mehling H, Melchior K, Menzel F, Münzel T, Natour M, Naudts I, Naumann R, Nischik R, Olbrich HG, Pohl W, Prohaska M, Proskynitopoulus N, Regner S, Reimer D, Roeder S, Rummel R, Salbach P, Schäfer T, Schaum T, Schenkenberger I, Schindler A, Schmidt A, Schmidt E, Schnabel A, Schneider R, Schneider W, Schreckenberg A, Schreibmüller F, Schreiner M, Schröder T, Schumacher M, Segner A, Seibert H, Siao G, Siao K, Sohn HY, Stöhring R, Tangerding G, Taubert G, Terhorst A, Tesch C, Toursarkissian N, Tyler K, Uebel P, Weyland K, Wilke A, Yilmaz A, Zemmrich C, Zeh W, Zotz R, Arango JL, Arriola J, Corona V, Leal S, López E, Muñoz R, Ovando A, Paniagua A, Rodríguez D, Velasquez L, Wyss F, Tse HF, Li SK, Yan B, Yip G, Merkely B, Andrassy G, Andreka P, Bakai J, Csapo K, Cziraki A, Édes I, Forster T, Hajko E, Illes A, Jánoskuti L, Kalina A, Kovacs Z, László Z, Lupkovics G, Matoltsy A, Müller G, Nagy A, Noori E, Nyolczas N, Papp A, Salamon C, Szántai G, Szocs A, Tomcsányi J, Toth D, Varjú I, Veress G, Vertes A, Zámolyi K, Zilahi Z, Andersen K, Gudnason T, Sigurdsson A, Thorgeirsson G, Abhyankar A, Agarwal D, Aggarwal R, Bagirath R, Banker D, Bisne V, Bohra P, Chopra V, Dani S, Dharmadhikari A, Fulwani M, Gadkari M, Ghaisas N, Basavanagowdappa H, Gupta S, Hiremath S, Jagtap P, Jain A, Jain V, Jindal R, Joseph S, Kerkar P, Kumbla M, Malipeddi B, Mathan G, Mehta A, Mohan M, Murthy L, Nair A, Pai V, Pandey A, Prakash V, Srinivasa Rao M, Srinivasa Rao N, Reddy N, Sarma P, Shah P, Shamsudden K, Sharma K, Sinha S, Thakkar B, Thanvi S, Trivedi P, Vijan V, Yugandhar B, Aronson D, Ben Gal T, Goland S, Katz A, Keren A, Lewis B, Marmor A, Mayler S, Shochat M, Senni M, Anastasio L, Baldin M, Brunelli C, Casolo G, Coppolino C, Cosmi F, Danzi G, Destro M, Di Napoli T, D'Ospina A, Fucili A, Gigantino A, Liberato NL, Lombardi F, Lembo G, Magrini F, Mannarino E, Marchese D, Minneci C, Modena MG, Mos L, Napoli T, Opasich C, Pajes G, Perticone F, Pileri PV, Poddighe G, Ronchi E, Saba PS, Sicuro M, Silvestri F, Uriarte AS, Spagnuolo V, Sprovieri M, Taddei S, Terrosu P, Tespili M, Uriarte J, Vergoni W, Volterrani M, Erglis A, Dormidontova G, Eglite R, Lvova T, Rancane G, Sime I, Petrulioniene Z, Luksiene D, Maleckas T, Mazutavicius R, Miliuniene R, Petrulioniene Z, Slapikas R, Ahmad W, Chew D, Ismail O, Ong T, Llamas EB, Aguilera M, Arenas J, Carrillo J, González J, Leon S, Llamas G, Macias A, Meaney A, Orihuela O, Pavía A, Rodriguez I, Rodriguez T, Salcido E, Solache G, Velasco R, Mosterd A, Basart D, Bellersen L, Derks A, Dijkgraaf R, Dunselman P, van Eck J, Gurlek C, den Hartog F, Hoedemaker G, Kaplan R, Koolen J, Liem L, Milhous J, de Nooijer C, Pronk A, Brunner-la Rocca H, Ronner E, Swart H, Tjeerdsma G, Willems F, Avilés E, Frago G, González B, Nieto R, Cabrera W, Alegre R, Azañero R, García JH, Godoy A, Heredia J, Lu L, Orihuela B, Rodriguez A, Roldan Y, Torres P, Urquiaga J, Sibulo AS Jr, Anonuevo J, Atilano A, Borromeo A, Castillo R, Chua P, Ferrolino A, Guerrero A, Locnen S, Manlutac B, Rogelio G, Rosita R, Ruales A, Vilela G, Negrusz-Kawecka M, Bebenek W, Sobkowicz B, Cymerman K, Dabrowska M, Foczpaniak M, Jazwinska-Tarnawska E, Kabara A, Kania G, Kolaczyk P, Kucharski W, Landa K, Mirek-Bryniarska E, Piepiorka M, Pijanowski Z, Sciborski R, Szpajer M, Tyminski M, Weglarz P, Wojciechowska C, Wronska D, Cardoso JS, Almeida F, Andrade A, Braganca N, Carvalho S, Fonseca C, Oliveira L, Padua F, Silvestre I, Soares R, Vinereanu D, Andor M, Bartos D, Basarab G, Coman I, Copaci I, Cristea M, Dragulescu S, Enache D, Fruntelata A, Iliescu L, Istratoaie O, Lighezan D, Militaru C, Nanea T, Nechita C, Puschita M, Tomescu M, Tudoran M, Boitsov S, Ageev F, Averkov O, Akimov A, Ballyuzek M, Baranov E, Baranova E, Barbarash O, Berkovich O, Berns S, Bessonova N, Boyarkin M, Bulashova O, Chernetsov V, Chukaeva I, Kamensky I, Dovgalevsky Y, Dovgolis S, Duplyakov D, Ermoshkina L, Fitilev S, Galyavich A, Gendlin G, Gofman A, Goloschekin B, Gomova T, Gordienko A, Karpov Y, Kastanayan A, Khromtsova O, Kisliak O, Kobalava Z, Konradi A, Korolev M, Kosmacheva E, Kostenko V, Koziolova N, Kuimov A, Kulibaba E, Lebedev P, Lesnov V, Libis R, Lopatin Y, Makukhin V, Masterov I, Moiseeva Y, Morozova T, Motylev I, Murashkina S, Nosov V, Oleynikov V, Palatkina T, Parmon E, Pimenov L, Privalov D, Rafalsky V, Rebrov A, Reznik I, Ruda M, Saifutdinov R, Sayganov S, Shvarts Y, Shpagina L, Shustov S, Shutemova E, Sitnikova M, Sizova J, Smolenskaya O, Solovieva A, Staroverov I, Struk R, Svistov A, Tarasov N, Tarlovskaya E, Tereschenko S, Trofimov N, Uspensky Y, Vasilieva E, Vezikova N, Vishnevsky A, Volkov D, Yakhontov D, Yakovlev A, Yavdosyuk A, Zateyshchikova A, Zharkov O, Zhilyaev E, Zotov D, Zrazhevsky K, Wong R, Lee C, Ong H, Yeo D, Dukát A, Antalík L, Baníková A, Demešová D, Dvoržák M, Fazekaš F, Foldiová D, Fülöp P, Kabaivanov P, Kovács J, Maček V, Majerčák I, Mazúr J, Mihalíková A, Olexa P, Pacherová J, Palinský M, Pálka J, Pella D, Remišová S, Schichorová J, Smik R, Sokolová B, Šuch S, Viňanská D, Burgess L, Ahmed F, Baben L, Badat A, Basson D, Bester F, Bruning A, Delport E, Dindar F, Foccart J, Gani M, Gerntholtz T, Hellstrom E, Horak A, Ismail S, Jamjam L, Kapp C, Latiff G, Lerumo T, Lombaard J, Manga P, van der Merwe N, Mkhwanazi M, Mohamed Z, Mpe M, Naidoo D, Padayachee T, Ranjith N, Jansen van Rensburg D, Saaiman J, Sebopa B, Tayob M, Theron H, Thomas M, Vally T, Venter T, Wellmann H, van Zyl L, Calvo C, Luis-Arias J, Arias-Castaño JC, Comín J, de Teresa L, Fernandez-Aviles F, Gomez-Huelgas R, González-Bueno M, Cosín J, Cremer D, Crespo M, Deben F, Freixa R, Galve E, Garcia M, Gomez R, Jiménez M, Mainar L, Marin I, Martinez F, Martínez-Sellés M, Marzal D, Muñoz B, Núñez J, Pascual D, Peña G, Reyes A, Sanmartín M, Torres F, Vida M, Fu M, Ahlström P, Hagerman I, Hajimirsadeghi A, Hansson A, Kempe A, Thorsén C, Zethson-Halldén M, Chen CH, Chen CP, Chen PS, Hsu KL, Lin LY, Pai PY, Tsao HM, Tzeng BH, Kiatchoosakun S, Hengrussamee K, Piyayotai D, Sanguanwong S, Thongsri T, Kozan O, Aktoz M, Barcin C, Birdane A, Camsari A, Ermis C, Guray Y, Kudat H, Ural D, Yavuzgil O, Yenigun M, Yigit Z, Yilmaz MB, Yokusoglu M, Squire I, Apostolakis S, Banerjee P, Barr C, Bhatia V, Bogle R, Boos C, Brigden G, Brown N, Bulugahapitiya S, Dayer M, Dutka D, El-Harari M, Fisher M, Gaballa M, Ghandi N, Glover J, James R, Kadr H, Kalra P, Kardos A, Lang C, Leslie S, Levy T, Lynch M, MacFadyen R, Mahmood S, Mamas M, Martin W, Megarry S, Mohindra R, More R, Moriarty A, Murphy J, Muthusamy R, Neyses L, Nightingale A, O'Toole L, Price D, Purvis J, Ryding A, Smith D, Sobolewska J, Soo L, Strain D, Trelawny J, Trevelyan J, Watkin R, Witherow F, Woldman S, Yousef Z, Starling R, Teerlink J, Adamson P, Akinboboye O, Akyea-Djamson A, Amin A, Amkieh A, Amos A, Anand I, Awasty V, Banish D, Bank A, Bargout R, Barnard D, Beacom M, Berg I, Berk M, Best J, Bilazarian S, Bouchard A, Bozkurt B, Breisblatt W, Brookfield L, Brown C, Browne K, Canadas-Zizzias R, Carr K, Chapman D, Chu A, Chung E, Colan D, Davis B, Denning S, Desai V, Dexter J, Dharma C, Edwards J, Efstratiadis S, Eisen H, Fattal P, Fenster B, Fernandez J, Flores A, Flores E, Floro J, Frivold G, Fuhs B, Goldscher D, Gould R, Grazette L, Laufer N, Lieber IH, Haas G, Habet K, Hack T, Haidar A, Halpern S, Hargrove J, Harris J, Hart T, Hass G, Hattler B, Hazelrigg M, Heilman K, Heiman M, Heroux A, Herzog W, Hoffman M, Hunter J, Iteld B, Jackson D, Jaffrani N, Janik M, Jardula M, Joseph J, Kaneshige A, Khan M, Klapholz M, Koren M, Kostis J, Larrain G, Lasala G, Laufer N, Lee K, Leonen M, Lieber I, Liu M, Magno J, Maher J, Maisel A, Maislos F, Malkowski M, Mallis G, Mandviwala M, Mani C, Markham D, Marple R, Maurer M, McKenzie W, Mehrle A, Mendez J, Miller A, Miller R, Miller V, Mishkin J, Mitchell J, Mody F, Montgomery B, Murray D, Murray A, Naidu J, Neutel J, Nguyen D, O'Brien T, Olsen S, Ooi H, Orchard R, Parrott C, Petersen J 2nd, Poling T, Prodafikas J, Ptacin M, Quinlan E 3rd, Quinn T, Rama B, Ramanathan K, Rawitscher D, Rosado J, Rosenthal S, Oberoi MS, Samal A, Schmalfuss C, Schwartz S, Seals A, Selektor Y, Schaefer S, Seto T, Shah S, Shanes J, Sims J, Singh S, Sooudi S, Sotolongo R, Suiter D, Sunderam S, Thadani U, Thrasher J, Trichon B, Vicuna R, Vranian R, Jackson R, Wallach S, Ward N, Weinstein D, Wells T, Wickemeyer W, Wight J, Williams C, Wu L, Xu G, Zebrack J, Mendoza I, Avendaño A, Alvarez M, Silva E, Vergara G, Hotchkiss D, Hunter C, Kim KS, Baek SH, Zo JH, Hong GR, Kang DH, Kang SM, Kim DS, Kim BJ, Kim U, Park DG, Shin JH, Yoo BS.

Abstract

BACKGROUND:

Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients.

METHODS AND RESULTS:

We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensin-converting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial. The analyses focused on prespecified measures of nonfatal clinical deterioration. In comparison with the enalapril group, fewer LCZ696-treated patients required intensification of medical treatment for heart failure (520 versus 604; hazard ratio, 0.84; 95% confidence interval, 0.74-0.94; P=0.003) or an emergency department visit for worsening heart failure (hazard ratio, 0.66; 95% confidence interval, 0.52-0.85; P=0.001). The patients in the LCZ696 group had 23% fewer hospitalizations for worsening heart failure (851 versus 1079; P<0.001) and were less likely to require intensive care (768 versus 879; 18% rate reduction, P=0.005), to receive intravenous positive inotropic agents (31% risk reduction, P<0.001), and to have implantation of a heart failure device or cardiac transplantation (22% risk reduction, P=0.07). The reduction in heart failure hospitalization with LCZ696 was evident within the first 30 days after randomization. Worsening of symptom scores in surviving patients was consistently more common in the enalapril group. LCZ696 led to an early and sustained reduction in biomarkers of myocardial wall stress and injury (N-terminal pro-B-type natriuretic peptide and troponin) versus enalapril.

CONCLUSIONS:

Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotensin-converting enzyme inhibition.

CLINICAL TRIAL REGISTRATION URL:

http://www.clinicaltrials.gov. Unique identifier: NCT01035255.

KEYWORDS:

heart failure; neprilysin; receptors, angiotensin

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center