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Lancet. 2010 Sep 11;376(9744):875-85. doi: 10.1016/S0140-6736(10)61198-1.

Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study.

Collaborators (784)

Swedberg K, Komajda M, Tavazzi L, Borer JS, Böhm M, Ford I, Dubost-Brama A, Lerebours G, Perrone S, Krum H, Van Mieghem W, Bocchi EA, Katova T, Liu P, Jalil J, Hu D, Vitovec J, Køber L, Uuetoa T, Niemela M, Jondeau G, Werdan K, Kremastinos D, Yu CM, Toth K, Rao DS, McDonald K, Metra M, Oh BH, Jirgenson J, Erglis A, Kavoluniene A, Sim KH, Voors AA, Dickstein K, Opolski G, Providencia L, Ionescu DD, Aroutiounov G, Hatala R, Sebestjen M, Aviles F, Willenheimer R, Oto A, Cowie M, Parkhomenko O, Lopez-Sendon JL, Dickstein K, Ponikowski P, Gavazzi A, Lopez de Sa E, Juanatey JR, Alings AM, Poole-Wilson P, Pocock S, Camm J, Nieminen M, Le Heuzey JY, Amuchastegui M, Barrios AR, Bendersky M, Beneítez CF, Buscema JJ, Labarta GB, Cacharrón JL, Caime JD, Colombo H, Colque RM, Costello AR, Diez F, Fernández A, Ferrari GM, Ferreyra R, Fuselli J, Gambarte AJ, Garrido M, Gorini NU, Carrillo NC, Guzmán L, Hasbani E, Jure HO, Kuschnir E, Lastiri H, Marquez LL, Luciardi HL, Luquez H, Majul CR, Marino J, Martingano R, Miriuka SG, Muntaner J, Perna E, Piasentin JA, Piskorz D, Pomposiello JC, Porcile R, Poy CA, Ramos HR, Acuña AA, Rusculleda M, Nisi JS, Sanchez JM, Sarjanovich R, Scaro G, Secchi JM, Severino P, Snitman MJ, Liprandi MI, Sultan MG, Vázquez RJ, Vigo CF, Vulcano N, Howes L, Jeffery I, Krum H, Rogers J, Russell A, Singh B, Soward A, Maurer G, Mörtl D, Castadot M, Chenu P, Cools F, Dendale P, Droogné W, El Allaf D, Gabriel L, Goethals M, Hollanders G, Mairesse GH, Materne P, Pierard L, Smeets JP, Smolders W, Troisfontaines P, Van Heddegem G, Van Mieghem W, Albuquerque DC, Almeida DR, Aziz JL, Boas FV, Bocchi EA, Bodanese LC, Braga JC, Chaves R, Figueiredo JC, Greco OT, Kohler I, Leaes PE, Mady C, Maia LN, Manenti E, Montera MW, Motta MS, Moura LZ, Precoma DB, Rassi S, Saraiva JF, Silveira JR, Filho DS, Teixeira M, Zimmermann SL, Benov H, Chobanska P, Chompalova B, Denchev S, Donova T, Georgiev B, Grigorov M, Hergeldjieva V, Kamenova Z, Karastanev K, Marchev S, Mihov L, Mileva A, Mincheva V, Petranov S, Popov A, Raev D, Sirakova V, Tisheva S, Torbova S, Tzekova M, Zlatareva N, Arnold JM, Bernstein V, Bhargava R, Bose S, Brossoit R, Ducharme A, Giannetti N, Grover A, Hill L, Kouz S, Labonté R, Liu P, Nawaz S, Proulx G, Savard D, Vizel S, Yao L, Bus AA, Bugueño C, Castro P, Cobos L, Escobar E, Moreno M, Castro CR, Schnettler MC, Sepúlveda P, Stockins B, Chen J, Cheng X, Gai L, Gao W, Guo T, Hong H, Hong L, Hu D, Huang D, Li H, Li L, Li L, Li T, Li W, Li X, Li X, Lin Y, Liu X, Luo K, Luo M, Ma G, Ma J, Pu X, Qi G, Qi X, Song J, Sun Y, Sun Y, Tang J, Wang H, Wang J, Wang M, Wang W, Wang X, Wei M, Wu S, Xu D, Yan X, Yang L, Yang T, Yang Y, Yao Z, Yuan Z, Zhang F, Zhang Y, Zhang Z, Zhao L, Zhao R, Zhao S, Ballek L, Bartůnková V, Cermák O, Drazka J, Fábik L, Filipenský B, Filipovský J, Galuszka J, Hanustiaková A, Herold M, Jerábek I, Jirka V, Kaislerová M, Malecha J, Marcinek G, Melenovský V, Pĕnicka M, Siegelová J, Skalická H, Sochor K, Soucek M, Spacek R, Spinar J, Spinarová L, Stípal R, Sulda M, Vencour D, Zajícek P, Brønnum-Schou J, Davidsen F, Dorph-Petersen A, Falstie-Jensen N, Gøtzsche O, Køber L, Korup E, Lederballe O, Nielsen T, Nyvad O, Rickers H, Roseva-Nielsen N, Skagen K, Larsen CT, Tuxen C, Videbaek L, Rasmussen OW, Averina O, Hedman A, Kaik J, Vahula V, Hällberg V, Karmakoski J, Kettunen P, Kettunen R, Melin J, Utriainen S, Vikström K, Ylitalo K, Belhassen L, Solal AC, Decoulx E, Delahaye F, Demarcq JM, El Mansour N, Funck F, Galinier M, Galley D, Gibelin P, Godenir JP, Gueffet JP, Guillot JP, De Mahenge AH, Jondeau G, Komajda M, Mansourati J, Martelet M, Mirode A, Ovize M, Roul G, Zannad F, Al-Zoebi A, Appel KF, Bauknecht C, Bergmann K, Böhm M, Deissner M, Dörr R, Drexler M, Förster A, Fries P, Genth-Zotz S, Grooterhorst P, Grötz J, Haustein G, Kleinertz K, Mitrovic V, Müller O, Patten M, Pospiech R, Proskynitopoulos N, Remppis A, Rummel R, Schenkenberger I, Schlegel F, Schmidt E, Schreckenberg A, Schwinger RH, Sechtem U, Spengler U, Taggeselle J, Weil J, Weissbrodt M, Werdan K, Zugck C, Anastasiou-Nana M, Christou A, Dimitroula V, Fotiadis I, Koliopoulos N, Kremastinos D, Kyriakides Z, Liagas K, Manolis A, Nanas I, Stakos D, Yu CM, Borbola J, Cziráki A, Czuriga I, Edes I, Herczeg B, Hunyady B, Józan-Jilling M, Juhász A, Kaló E, Katona A, Kiss RG, Kósa I, Kovács A, Kovács Z, Lakatos F, Lippai J, Lupkovics G, Matoltsy A, Mohácsi A, Nagy A, Nyárádi A, Pálinkás A, Pálvölgyi N, Rumi G, Sereg M, Takács J, Tomcsányi J, Tóth K, Veress G, Vértes A, Zámolyi K, Gadkari MA, Gowdappa HB, Hardas SP, Janorkar SS, Mehrotra S, Prasad GN, Puri VK, Rajasekar V, Rao VS, Reddy GV, Kumar PS, Rao DS, Sinha N, Crean P, Mahon N, McAdam B, McDonald K, Nash P, Agostoni P, Astarita C, Campana C, Dei Cas L, Ferrari R, Filorizzo G, Fragasso G, Gaspardone A, Giovannini E, Indolfi C, La Rovere MT, Ieva M, Lombardi F, Petacchi R, Pettinati G, Pirelli S, Pulignano G, Renaldini E, Scelsi L, Scrutino D, Spinnler MT, Tavazzi L, Vanoli E, Vassanelli C, Vitale C, Baika A, Erglis A, Gersamija A, Libins A, Ozolina MA, Pontaga N, Rancane G, Strizko I, Anusauskiene J, Dailydkiene A, Grabauskiene V, Kavoliuniene A, Kibarskis A, Kirkutis A, Maslauskaite-Voluckiene EE, Vasiliauskas DA, Chew DS, Sim KH, wan Ahmad WA, Alings AM, Bartels GL, Cornel JH, Daniels MC, Dirkali A, Herrman JP, Herweijer A, Hoedemaker G, Holwerda NJ, Hoogslag PA, Jerzewski A, Kok WE, Kuijper AF, Lenderink T, Lionarons RJ, Michels HR, Nierop PR, Nijland F, Pieterse MG, Plomp J, Ramanna H, Van Boven AJ, Van der Meer P, Van Kempen LH, Van Vlies B, Van Wijk LM, Voors AA, Wesdorp JC, Willems FF, Withagen AJ, Zwart P, Agewall S, Atar D, Dickstein K, Grundtvig M, Gundersen T, Omland TM, Otterstad JE, Werner EL, Westheim A, Andrzejak R, Bronisz M, Cymerman K, Dluzniewski M, Gasior Z, Gorny J, Grodzicki T, Janion M, Kalarus Z, Kania G, Kawecka-Jaszcz K, Kawka-Urbanek T, Kolodziej P, Korewicki J, Krynicki R, Krzciuk M, Krzeminska-Pakula M, Kurowski M, Miekus P, Musial W, Opolski G, Piepiorka M, Piwowarska W, Pluta W, Pulkowski G, Ruminski W, Ruzyllo W, Rynkiewicz A, Sadowski J, Sinkiewicz S, Szachniewicz J, Szolkiewicz M, Szpajer M, Targonski R, Tendera M, Trojnar R, Trusz-Gluza M, Turek P, Wardega T, Wodniecki J, Wrzosek B, Wysocki H, Zmudka K, Bettencourt P, Gil V, Morais J, Lopes JP, Providência L, Sarmento P, Gomes RS, Aron G, Arsenescu C, Avram R, Carasca E, Cinteza M, Datcu M, Dimulescu DR, Dragomir D, Ionascu-Fometescu R, Ionescu DD, Kiss L, Macarie C, Manitiu I, Minescu B, Opris MM, Pop C, Radoi M, Radu I, Sinescu CJ, Tanaseanu CM, Tase A, Tomescu M, Topolnitchi L, Vintila M, Vladoianu M, Zdrenghea D, Arkhipov M, Aroutiounov G, Barbarash O, Butko D, Chukaeva I, Chumakova G, Fomin I, Glezer M, Gorbachenkov A, Gordeev I, Gorokhovskaya G, Kazakevich E, Kobalava J, Koziolova N, Kuimov A, Lopatin Y, Mareev V, Martyushov S, Moiseeva O, Narusov O, Nedogoda S, Obrezan A, Olbinskaya L, Pavlyukova EN, Petrov A, Pimenov L, Rebrov A, Rodoman G, Sayfutdinov R, Sayganov S, Schekotov V, Scherbak A, Semernin E, Shalaev S, Shpektor A, Shvarts Y, Sizova Z, Skvortsov A, Smolenskaya O, Soloviev O, Stryuk R, Suvorov A, Tankhilevich B, Tarlovskaya E, Tereschenko S, Tsyba L, Turin V, Turina T, Yakhontova P, Yakusevich V, Zemtsovsky EV, Baníková A, Bugán V, Fabián J, Filipová S, Goncalvesová E, Hatala R, Kmec J, Kokles M, Palko S, Vahala P, Flezar M, Lainscak M, Markez J, Sebestjen M, Mocnik FS, Pusnik CS, Veternik-Debeljak A, Baek SH, Chae JK, Chae SC, Cho MC, Choi DJ, Ha JW, Han KR, Jeon ES, Kim DS, Kim HJ, Kim JJ, Kim KS, Lee SH, Lim DS, Oh BH, Oh SJ, Park JC, Ryu KH, Shin MS, Yang JY, Yoo BS, Bethencourt A, Cortada JB, de Berrazueta JR, Galan Lde L, Galve E, Maqueda IG, Navarro MJ, Aranda VL, Macaya CM, Luengo CM, Selles MM, Aguilera RM, Rabadán IR, Román AV, Ahremark U, Akesson H, Al-Khalili F, Andersson B, Angman K, Bandh S, Boström PA, Braunschweig F, Ellström J, Johansson L, Kronvall T, Larnefeldt H, Larsson LE, Ljungberg J, Lycksell M, Näslund U, Ohlin H, Persson H, Peterson M, Radeberg M, Rydberg E, Söderberg S, Stjerna A, Swedberg K, Timberg I, Ullman B, Wikström G, Akarturk E, Erol MK, Gurgun C, Kozan O, Mutlu B, Sahin M, Sonmez K, Yilmaz H, Cowie M, Davies A, Groves P, Hudson I, McCann G, Moriarty A, Purvis J, Squire I, Travill C, Amosova K, Bazylevych A, Bula L, Dzyak G, Girina O, Glushko L, Goloborodko B, Ignatenko G, Karpenko O, Korkushko O, Korzh O, Kovalenko V, Kovalsky I, Kraydashenko O, Krayz I, Kubyshkin V, Kuryata O, Levchenko O, Mostovoy Y, Parkhomenko O, Pertseva T, Popyk G, Prerepelytsya M, Rishko M, Rudenko L, Rudyk Y, Sakharchuk I, Serkova V, Sharuk O, Soldatchenko S, Storozhuk B, Sychov O, Syvolap V, Tashchuk V, Tseluyko V, Vatutin M, Vizir V, Vlasenko M, Voronkov L, Yagensky A, Zavgorodniy A, Zharinov O.

Author information

  • 1Department of Emergency and Cardiovascular Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden. karl.swedberg@gu.se

Erratum in

  • Lancet. 2010 Dec 11;376(9757):1988. Lajnscak, M [corrected to Lainscak, M]; Rabanedo, I Roldan [corrected to Rabadán, I Roldan]; Leva, M [corrected to Ieva, M].

Abstract

BACKGROUND:

Chronic heart failure is associated with high mortality and morbidity. Raised resting heart rate is a risk factor for adverse outcomes. We aimed to assess the effect of heart-rate reduction by the selective sinus-node inhibitor ivabradine on outcomes in heart failure.

METHODS:

Patients were eligible for participation in this randomised, double-blind, placebo-controlled, parallel-group study if they had symptomatic heart failure and a left-ventricular ejection fraction of 35% or lower, were in sinus rhythm with heart rate 70 beats per min or higher, had been admitted to hospital for heart failure within the previous year, and were on stable background treatment including a β blocker if tolerated. Patients were randomly assigned by computer-generated allocation schedule to ivabradine titrated to a maximum of 7.5 mg twice daily or matching placebo. Patients and investigators were masked to treatment allocation. The primary endpoint was the composite of cardiovascular death or hospital admission for worsening heart failure. Analysis was by intention to treat. This trial is registered, number ISRCTN70429960.

FINDINGS:

6558 patients were randomly assigned to treatment groups (3268 ivabradine, 3290 placebo). Data were available for analysis for 3241 patients in the ivabradine group and 3264 patients allocated placebo. Median follow-up was 22.9 (IQR 18-28) months. 793 (24%) patients in the ivabradine group and 937 (29%) of those taking placebo had a primary endpoint event (HR 0.82, 95% CI 0.75-0.90, p<0.0001). The effects were driven mainly by hospital admissions for worsening heart failure (672 [21%] placebo vs 514 [16%] ivabradine; HR 0.74, 0.66-0.83; p<0.0001) and deaths due to heart failure (151 [5%] vs 113 [3%]; HR 0.74, 0.58-0.94, p=0.014). Fewer serious adverse events occurred in the ivabradine group (3388 events) than in the placebo group (3847; p=0.025). 150 (5%) of ivabradine patients had symptomatic bradycardia compared with 32 (1%) of the placebo group (p<0.0001). Visual side-effects (phosphenes) were reported by 89 (3%) of patients on ivabradine and 17 (1%) on placebo (p<0.0001).

INTERPRETATION:

Our results support the importance of heart-rate reduction with ivabradine for improvement of clinical outcomes in heart failure and confirm the important role of heart rate in the pathophysiology of this disorder.

FUNDING:

Servier, France.

Copyright 2010 Elsevier Ltd. All rights reserved.

Comment in

PMID:
20801500
[PubMed - indexed for MEDLINE]
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