Document Detail


Dronedarone in high-risk permanent atrial fibrillation.
MedLine Citation:
PMID:  22082198     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular antiarrhythmic effects. We hypothesized that dronedarone would reduce major vascular events in high-risk permanent atrial fibrillation.
METHODS: We assigned patients who were at least 65 years of age with at least a 6-month history of permanent atrial fibrillation and risk factors for major vascular events to receive dronedarone or placebo. The first coprimary outcome was stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes. The second coprimary outcome was unplanned hospitalization for a cardiovascular cause or death.
RESULTS: After the enrollment of 3236 patients, the study was stopped for safety reasons. The first coprimary outcome occurred in 43 patients receiving dronedarone and 19 receiving placebo (hazard ratio, 2.29; 95% confidence interval [CI], 1.34 to 3.94; P=0.002). There were 21 deaths from cardiovascular causes in the dronedarone group and 10 in the placebo group (hazard ratio, 2.11; 95% CI, 1.00 to 4.49; P=0.046), including death from arrhythmia in 13 patients and 4 patients, respectively (hazard ratio, 3.26; 95% CI, 1.06 to 10.00; P=0.03). Stroke occurred in 23 patients in the dronedarone group and 10 in the placebo group (hazard ratio, 2.32; 95% CI, 1.11 to 4.88; P=0.02). Hospitalization for heart failure occurred in 43 patients in the dronedarone group and 24 in the placebo group (hazard ratio, 1.81; 95% CI, 1.10 to 2.99; P=0.02).
CONCLUSIONS: Dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent atrial fibrillation who were at risk for major vascular events. Our data show that this drug should not be used in such patients. (Funded by Sanofi-Aventis; PALLAS ClinicalTrials.gov number, NCT01151137.).
Authors:
Stuart J Connolly; A John Camm; Jonathan L Halperin; Campbell Joyner; Marco Alings; John Amerena; Dan Atar; Álvaro Avezum; Per Blomström; Martin Borggrefe; Andrzej Budaj; Shih-Ann Chen; Chi Keong Ching; Patrick Commerford; Antonio Dans; Jean-Marc Davy; Etienne Delacrétaz; Giuseppe Di Pasquale; Rafael Diaz; Paul Dorian; Greg Flaker; Sergey Golitsyn; Antonio Gonzalez-Hermosillo; Christopher B Granger; Hein Heidbüchel; Josef Kautzner; June Soo Kim; Fernando Lanas; Basil S Lewis; Jose L Merino; Carlos Morillo; Jan Murin; Calambur Narasimhan; Ernesto Paolasso; Alexander Parkhomenko; Nicholas S Peters; Kui-Hian Sim; Martin K Stiles; Supachai Tanomsup; Lauri Toivonen; János Tomcsányi; Christian Torp-Pedersen; Hung-Fat Tse; Panos Vardas; Dragos Vinereanu; Denis Xavier; Jun Zhu; Jun-Ren Zhu; Lydie Baret-Cormel; Estelle Weinling; Christoph Staiger; Salim Yusuf; Susan Chrolavicius; Rizwan Afzal; Stefan H Hohnloser;
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Publication Detail:
Type:  Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2011-11-14
Journal Detail:
Title:  The New England journal of medicine     Volume:  365     ISSN:  1533-4406     ISO Abbreviation:  N. Engl. J. Med.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-15     Completed Date:  2011-12-22     Revised Date:  2012-04-26    
Medline Journal Info:
Nlm Unique ID:  0255562     Medline TA:  N Engl J Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2268-76     Citation Subset:  AIM; IM    
Affiliation:
Population Health Research Institute, Hamilton Health Sciences, Hamilton, ON L8L 2X2, Canada. connostu@phri.ca
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT01151137
Export Citation:
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MeSH Terms
Descriptor/Qualifier:
Aged
Aged, 80 and over
Amiodarone / adverse effects,  analogs & derivatives*,  therapeutic use
Anti-Arrhythmia Agents / adverse effects,  blood,  therapeutic use*
Atrial Fibrillation / blood,  drug therapy*
Atrial Flutter / drug therapy
Cardiovascular Diseases / chemically induced,  mortality
Chronic Disease
Digoxin / blood,  therapeutic use
Double-Blind Method
Drug Therapy, Combination
Female
Follow-Up Studies
Heart Failure / chemically induced,  epidemiology
Heart Rate / drug effects
Hospitalization / statistics & numerical data
Humans
Male
Risk Factors
Stroke / chemically induced,  epidemiology
Chemical
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 0/dronedarone; 1951-25-3/Amiodarone; 20830-75-5/Digoxin
Investigator
Investigator/Affiliation:
D G Wyse / ; J Cairns / ; M Pfeffer / ; S Pocock / ; H Wellens / ; M Atra / ; A Avezum / ; D C G Basart / ; N M Bornstein / ; A Brandes / ; H De Raedt / ; D Doiny / ; G Z Duray / ; H Dvorakova / ; A Estrada / ; G Fodor / ; B Gross / ; D Halon / ; O Häppölä / ; R Hart / ; J S Healey / ; F Jacobsson / ; C Joyner / ; P Kalvach / ; A Krahn / ; M Laine / ; A P Maggioni / ; G H Mairesse / ; S W Muir / ; B Norrving / ; A Peeters / ; G Pizzolato / ; G Ruiz-Ares / ; C Torp-Pedersen / ; C Veltmann / ; P Verdecchia / ; P Widimsky / ; J Zaborski / ; R Zimlichman / ; B Demaerschalk / ; H C Diener / ; R Hart / ; D Tirschwell / ; S Chrolavicius / ; E Holmes / ; M Lawrence / ; S Bajkor / ; T McCready / ; B Meeks / ; R Afzal / ; P Gao / ; J Smith / ; X Yang / ; F Yuan / ; L Blake / ; V Dunlop / ; Z Gasic / ; S Molnar / ; R Nieuwlaat / ; E Pasadyn / ; J Sephton / ; R Tuhy / ; M Wild / ; A Caccavo / ; L R Cartasegna / ; C A Cuneo / ; M A Garrido / ; L A Guzman / ; M A Hominal / ; J R Llanos / ; I J MacKinnon / ; M L Vico / ; D R Vogel / ; C J Zaidman / ; D Colquhoun / ; J T Counsell / ; F J de Looze / ; V K Durbidge / ; P W Purnell / ; A L Soward / ; W J van Gaal / ; M William / ; D Burkart-Kuettner / ; K Huber / ; B Pieske / ; F X Roithinger / ; E M Catez / ; F J C Cools / ; L De Roy / ; P De Vusser / ; L De Wolf / ; O Deceuninck / ; D Dilling-Boer / ; M P Goethals / ; G H Mairesse / ; G Paparella / ; F Provenier / ; C Scavée / ; G Vervoort / ; R V Botelho / ; J S Braga / ; A A de Paola / ; W K S B de Souza / ; P R Genta / ; M E Hernandes / ; J Jaber / ; A M Lorga-Filho / ; E R Manenti / ; J C Moura Jorge / ; D B Précoma / ; G Reis / ; P R Rossi / ; A C S Sousa / ; S L Zimmermann / ; N I Gronkova / ; H S Tumbev / ; S Bose / ; P Boucher / ; J Y Cha / ; C M Constance / ; P Costi / ; B Coutu / ; M Gupta / ; J S Healey / ; S Kouz / ; A S Lam / ; R Leather / ; A S Pandey / ; T Rebane / ; D Savard / ; R St-Hilaire / ; S Vizel / ; J L Cobos / ; R Corbalan / ; H Donoso / ; E Escobar / ; M E Medina / ; S H Potthoff / ; C A Raffo / ; J G Saavedra / ; M A Tijerino / ; L Ballek / ; P Boček / ; M Choura / ; V Dědek / ; A Egert / ; M Hudcovic / ; Z Klimsa / ; R Labrova / ; J Malecha / ; I Petrova / ; I Podpera / ; Z Poklopová / ; T Velimsky / ; A Brandes / ; U Dixen / ; K Egstrup / ; L Frost / ; G Gislason / ; S E Husted / ; T J Jakobsen / ; J Jeppesen / ; K Kaae Dodt / ; K K Klarlund / ; T M Melchior / ; H Nielsen / ; K Skagen / ; A Aro / ; H V Huikuri / ; V Kyto / ; K Nyman / ; S Utriainen / ; A Ylitalo / ; R Fouche / ; K Gacem / ; M Mansour / ; J L Pasquie / ; J E Poulard / ; K F Appel / ; C Axthelm / ; R F Bosch / ; P Bushoven / ; H Darius / ; G C Grönefeld / ; C Hanefeld / ; W Haverkamp / ; T Horacek / ; C W Israel / ; H Killat / ; T Klingenheben / ; J Kreuzer / ; M Leicht / ; M B Licka / ; M Niethammer / ; W A Rieker / ; P Salbach / ; I Schenkenberger / ; A Schmidt / ; S G Spitzer / ; N Toursarkissian / ; R Veltkamp / ; C Veltmann / ; M Weissbrodt / ; B R Winkelmann / ; J Wurziger / ; C Zemmrich / ; I A Vogiatzis / ; C W Siu / ; G Z Duray / ; G Ferencz / ; A Katona / ; K Keltai / ; Z Kovács / ; Z Laszlo / ; F Poor / ; I Szakal / ; E Toldy-Schedel / ; A Vertes / ; S Atar / ; M Eldar / ; M Elias / ; N A Freedberg / ; S Halabi / ; S Hamoud / ; A Katz / ; E E Klainman / ; A Marmor / ; A Medina / ; M Mosseri / ; M Motro / ; G Y Stein / ; T Weiss / ; D Zeltser / ; R Zimlichman / ; D Calabrese / ; F Cosmi / ; F de Tommasi / ; N Glorioso / ; M M Gulizia / ; M Mennuni / ; G Piovaccari / ; P Verdecchia / ; K H Chee / ; M A Alcocer Gamba / ; R Alvarado-Ruiz / ; J L Arenas / ; E Bayram Llamas / ; C G Calvo Vargas / ; J Carrillo / ; P Fernandez-Bonetti / ; J F Gomez / ; G Llamas-Esperón / ; E Lopez Rosas / ; N Matadamas Hernandez / ; J M Ramirez Isunza / ; E Salcido / ; R G Velasco-Sanchez / ; G L Bartels / ; D C G Basart / ; F Bracke / ; T A Bruning / ; L Cozijnsen / ; G J de Weerd / ; F R den Hartog / ; H Geertman / ; K Hamraoui / ; W F Heesen / ; I Hunze / ; H H D Idzerda / ; J Kragten / ; A H Liem / ; D J Lok / ; A Moens / ; J Plomp / ; L Pos / ; A R Ramdat Misier / ; J J Remmen / ; J H Ruiter / ; M F Scholten / ; H P Swart / ; J G M Tans / ; L Theunissen / ; R Tukkie / ; R van der Heijden / ; D J Van Doorn / ; I C Van Gelder / ; M W J van Hessen / ; P H M Westendorp / ; A R Willems / ; S K Zoet-Nugteren / ; S A Aitken / ; J M Elliott / ; J E Scales / ; B Scott / ; I F Ternouth / ; J Tisch / ; J Berg-Johansen / ; M A Husvik / ; H Istad / ; K Risberg / ; R Rød / ; P A Sirnes / ; G K Skjelvan / ; J Bednarski / ; M Bronisz / ; L Bryniarski / ; J R Gniot / ; T Kawka-Urbanek / ; J Kopaczewski / ; P Miekus / ; T J Pasierski / ; M Piepiorka / ; F Prochaczek / ; G Raczak / ; J Rekosz / ; J Stepinska / ; R Szelemej / ; M Szpajer / ; B Zaborska / ; M A Cinteza / ; A O Ciobanu / ; A R Dan / ; D Dimulescu / ; C G Fierbinteanu-Braticevici / ; O Istratoaie / ; D F Lighezan / ; B Minescu / ; M M Vintila / ; N M Akhmedzhanov / ; B A Alikhanov / ; A V Barabashkina / ; O Barbarash / ; V B Barbarich / ; B Y Bart / ; M V Boyarkin / ; N N Burova / ; L Bychkova / ; S B Fitilev / ; T P Gizatulina / ; L A Khaisheva / ; V O Konstantinov / ; N Koziolova / ; V Lesnov / ; Y Lukyanov / ; N P Lyamina / ; T A Malkina / ; O N Miller / ; V Moiseev / ; N V Novikova / ; O V Orlikova / ; V A Orlov / ; M F Osipenko / ; E Panchenko / ; D Y Platonov / ; S V Popov / ; V V Rafalakiy / ; M Y Ruda / ; S A Seliverstova / ; S V Shalaev / ; V V Shchekotov / ; Y Shubik / ; Y Shvarts / ; V A Sulimov / ; T V Tretyakova / ; S Vaniev / ; A Vishnevsky / ; V V Yakusevich / ; S S Yakushin / ; K N Zrazhevskiy / ; W S Teo / ; V Bugan / ; G Kaliská / ; M Masarovičová / ; J Nociar / ; D Pella / ; R Uhliar / ; M Bushidi / ; J M Engelbrecht / ; A M Okreglicki / ; T Pillay / ; F A Snyders / ; H D Theron / ; T P Venter / ; J G Cho / ; D Kim / ; Y H Kim / ; M H Lee / ; S Oh / ; Y K On / ; T H Rho / ; D H Shin / ; J Alzueta / ; J Bruguera / ; S Castrejon / ; E Díaz-Infante / ; L Grigorian Shamagian / ; A Martínez-Rubio / ; L Mont / ; M Vida / ; X Viñolas / ; S T Berglund / ; C Blomstrom-Lundqvist / ; P Cherfan / ; F Jacobsson / ; S Jakobsson / ; L Johansson / ; T Juhlin / ; P Kozak / ; F Rönn / ; M Rosenqvist / ; L Sprock / ; A F Gallino / ; P A Lyrer / ; T Moccetti / ; M C Chen / ; Y F Hu / ; J L Lin / ; M S Wen / ; O I Karpenko / ; S Kozhukhov / ; I Kraiz / ; S S Pavlyk / ; P I Potapenko / ; O V Prokhorov / ; I V Prudkyi / ; V Y Prykhodko / ; L V Rudenko / ; O S Sychov / ; V I Tseluyko / ; V A Vizir / ; O J Zharinov / ; R Aggarwal / ; A J Copley / ; P P Davey / ; H H Kadr / ; G Y H Lip / ; S Lord / ; A J Moriarty / ; S W Muir / ; M P Pye / ; A D Ryding / ; I Savelieva / ; R Abadier / ; S Ahmad / ; Z M Ahmad / ; K P Alexander / ; A D Alfieri / ; S Baker / ; E M Ball / ; L Baruch / ; R P Bellam / ; S A Benjamin / ; D A Brill / ; K F Browne / ; J T Call / ; K W Carr / ; H Chandna / ; C Chen / ; Y C J Chen / ; V S Chilakapati / ; D Colan / ; S F Cossu / ; J Dean / ; S P DeFehr / ; S J Dempsey / ; V S Desai / ; M L Dohrmann / ; H S Ellison / ; G Emlein / ; N Farris / ; R H Fields / ; G J Fishbein / ; E A Flores / ; I R Friedlander / ; M D Gelernt / ; H C Genovely / ; E L Gillespie / ; B M Go / ; D W Gottlieb / ; P G Grena / ; T Guarnieri / ; D K Gupta / ; A A Haidar / ; G S Hamroff / ; J L Hargrove / ; E J Haskel / ; S E Hearne / ; D A Henderson / ; J M Herre / ; W R Herzog / ; B L Hoppe / ; D Hotchkiss / ; D J Humiston / ; P G Igic / ; B K Jackson / ; A K Jacobson / ; N A Jaffrani / ; D Jarzabkowski / ; M R Jazayeri / ; A J Kaplan / ; R N Khant / ; A C Kim / ; K A Klancke / ; E J Kosinski / ; M Kovach / ; J H Kramer / ; E W Lader / ; J A LeLevier / ; N E Lepor / ; R M Levy / ; R H Littlefield / ; R N Marple / ; F A McGrew / ; M J McWilliams / ; A Meholick / ; M J Mirro / ; J F Murphy / ; A V Murray / ; V K Nadar / ; M Nanna / ; A J Navarrete-Casas / ; D J O'Dea / ; P G O'Neill / ; S R Oza / ; R J Patel / ; N S Perlmutter / ; D L Pierce / ; S D Promisloff / ; J G Pulido / ; J Rahman / ; D V Rhodes / ; A M Rubin / ; J H Sandberg / ; C M Sandesara / ; R Schreiman / ; A Shah / ; K H Sheikh / ; N Singh / ; S B Sloan / ; C W Sofley / ; C S Staniloae / ; J M Teixeira / ; W M Tuan / ; B R Vaid / ; R M Vicari / ; N K Vijay / ; K N Vora / ; R J Weiss / ; H S Wenocur / ; A Yunus /
Comments/Corrections
Comment In:
Nat Rev Cardiol. 2012 Jan;9(1):5   [PMID:  22124322 ]
N Engl J Med. 2012 Mar 22;366(12):1159-60; author reply 1161   [PMID:  22435379 ]
N Engl J Med. 2012 Mar 22;366(12):1160; author reply 1161   [PMID:  22435380 ]
N Engl J Med. 2012 Mar 22;366(12):1160-1   [PMID:  22435381 ]
Praxis (Bern 1994). 2012 Mar 28;101(7):491-2   [PMID:  22454313 ]
Expert Opin Pharmacother. 2012 Apr;13(6):867-71   [PMID:  22424264 ]
N Engl J Med. 2012 Mar 22;366(12):1159; author reply 1161   [PMID:  22435378 ]
N Engl J Med. 2011 Dec 15;365(24):2321-2   [PMID:  22082122 ]
Erratum In:
N Engl J Med. 2012 Feb 16;366(7):672

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