Outcomes of digoxin vs. beta blocker in atrial fibrillation: report from ESC–EHRA EORP AF Long-Term General Registry
Authors: Ding Wern Yew , Boriani Giuseppe , Marin Francisco , Blomström-Lundqvist Carina , Potpara Tatjana S , Fauchier Laurent , Lip Gregory Y H ,   ESC–EHRA EORP AF Long-Term General Registry Investigators, Boriani (Chair) G , Lip G Y H , Tavazzi L , Maggioni A P , Dan G-A , Potpara T , Nabauer M , Marin F , Kalarus Z , Fauchier L , Goda A , Mairesse G , Shalganov T , Antoniades L , Taborsky M , Riahi S , Muda P , Bolao I García , Piot O , Nabauer M , Etsadashvili K , Simantirakis E , Haim M , Azhari A , Najafian J , Santini M , Mirrakhimov E , Kulzida K a , Erglis A , Poposka L , Burg M , Crijns H , Erküner Ö , Atar D , Lenarczyk R , Oliveira M Martins , Shah D , Dan G-A , Serdechnaya E , Potpara T , Diker E , Lip G Y H , Lane D , Zëra E , Ekmekçiu U , Paparisto V , Tase M , Gjergo H , Dragoti J , Goda A , Ciutea M , Ahadi N , el Husseini Z , Raepers M , Leroy J , Haushan P , Jourdan A , Lepiece C , Desteghe L , Vijgen J , Koopman P , Van Genechten G , Heidbuchel H , Boussy T , De Coninck M , Van Eeckhoutte H , Bouckaert N , Friart A , Boreux J , Arend C , Evrard P , Stefan L , Hoffer E , Herzet J , Massoz M , Celentano C , Sprynger M , Pierard L , Melon P , Van Hauwaert B , Kuppens C , Faes D , Van Lier D , Van Dorpe A , Gerardy A , Deceuninck O , Xhaet O , Dormal F , Ballant E , Blommaert D , Yakova D , Hristov M , Yncheva T , Stancheva N , Tisheva S , Tokmakova M , Nikolov F , Gencheva D , Shalganov T , Kunev B , Stoyanov M , Marchov D , Gelev V , Traykov V , Kisheva A , Tsvyatkov H , Shtereva R , Bakalska-Georgieva S , Slavcheva S , Yotov Y , Kubíčková M , Marni Joensen A , Gammelmark A , Rasmussen L Hvilsted , Dinesen P , Riahi S , Venø S Krogh , Sorensen B , Korsgaard A , Andersen K , Hellum C Fragtrup , Svenningsen A , Nyvad O , Wiggers P , May O , Aarup A , Graversen B , Jensen L , Andersen M , Svejgaard M , Vester S , Hansen S , Lynggaard V , Ciudad M , Vettus R , Muda P , Maestre A , Castaño S , Cheggour S , Poulard J , Mouquet V , Leparrée S , Bouet J , Taieb J , Doucy A , Duquenne H , Furber A , Dupuis J , Rautureau J , Font M , Damiano P , Lacrimini M , Abalea J , Boismal S , Menez T , Mansourati J , Range G , Gorka H , Laure C , Vassalière C , Elbaz N , Lellouche N , Djouadi K , Roubille F , Dietz D , Davy J , Granier M , Winum P , Leperchois-Jacquey C , Kassim H , Marijon E , Le Heuzey J , Fedida J , Maupain C , Himbert C , Gandjbakhch E , Hidden-Lucet F , Duthoit G , Badenco N , Chastre T , Waintraub X , Oudihat M , Lacoste J , Stephan C , Bader H , Delarche N , Giry L , Arnaud D , Lopez C , Boury F , Brunello I , Lefèvre M , Mingam R , Haissaguerre M , Le Bidan M , Pavin D , Le Moal V , Leclercq C , Piot O , Beitar T , Martel I , Schmid A , Sadki N , Romeyer-Bouchard C , Da Costa A , Arnault I , Boyer M , Piat C , Fauchier L , Lozance N , Nastevska S , Doneva A , Fortomaroska Milevska B , Sheshoski B , Petroska K , Taneska N , Bakrecheski N , Lazarovska K , Jovevska S , Ristovski V , Antovski A , Lazarova E , Kotlar I , Taleski J , Poposka L , Kedev S , Zlatanovik N , Jordanova S , Bajraktarova Proseva T , Doncovska S , Maisuradze D , Esakia A , Sagirashvili E , Lartsuliani K , Natelashvili N , Gumberidze N , Gvenetadze R , Etsadashvili K , Gotonelia N , Kuridze N , Papiashvili G , Menabde I , Glöggler S , Napp A , Lebherz C , Romero H , Schmitz K , Berger M , Zink M , Köster S , Sachse J , Vonderhagen E , Soiron G , Mischke K , Reith R , Schneider M , Rieker W , Boscher D , Taschareck A , Beer A , Oster D , Ritter O , Adamczewski J , Walter S , Frommhold A , Luckner E , Richter J , Schellner M , Landgraf S , Bartholome S , Naumann R , Schoeler J , Westermeier D , William F , Wilhelm K , Maerkl M , Oekinghaus R , Denart M , Kriete M , Tebbe U , Scheibner T , Gruber M , Gerlach A , Beckendorf C , Anneken L , Arnold M , Lengerer S , Bal Z , Uecker C , Förtsch H , Fechner S , Mages V , Martens E , Methe H , Schmidt T , Schaeffer B , Hoffmann B , Moser J , Heitmann K , Willems S , Willems S , Klaus C , Lange I , Durak M , Esen E , Mibach F , Mibach H , Utech A , Gabelmann M , Stumm R , Ländle V , Gartner C , Goerg C , Kaul N , Messer S , Burkhardt D , Sander C , Orthen R , Kaes S , Baumer A , Dodos F , Barth A , Schaeffer G , Gaertner J , Winkler J , Fahrig A , Aring J , Wenzel I , Steiner S , Kliesch A , Kratz E , Winter K , Schneider P , Haag A , Mutscher I , Bosch R , Taggeselle J , Meixner S , Schnabel A , Shamalla A , Hötz H , Korinth A , Rheinert C , Mehltretter G , Schön B , Schön N , Starflinger A , Englmann E , Baytok G , Laschinger T , Ritscher G , Gerth A , Dechering D , Eckardt L , Kuhlmann M , Proskynitopoulos N , Brunn J , Foth K , Axthelm C , Hohensee H , Eberhard K , Turbanisch S , Hassler N , Koestler A , Stenzel G , Kschiwan D , Schwefer M , Neiner S , Hettwer S , Haeussler-Schuchardt M , Degenhardt R , Sennhenn S , Steiner S , Brendel M , Stoehr A , Widjaja W , Loehndorf S , Logemann A , Hoskamp J , Grundt J , Block M , Ulrych R , Reithmeier A , Panagopoulos V , Martignani C , Bernucci D , Fantecchi E , Diemberger I , Ziacchi M , Biffi M , Cimaglia P , Frisoni J , Boriani G , Giannini I , Boni S , Fumagalli S , Pupo S , Di Chiara A , Mirone P , Fantecchi E , Boriani G , Pesce F , Zoccali C , Malavasi V L , Mussagaliyeva A , Ahyt B , Salihova Z , Koshum-Bayeva K , Kerimkulova A , Bairamukova A , Mirrakhimov E , Lurina B , Zuzans R , Jegere S , Mintale I , Kupics K , Jubele K , Erglis A , Kalejs O , Vanhear K , Burg M , Cachia M , Abela E , Warwicker S , Tabone T , Xuereb R , Asanovic D , Drakalovic D , Vukmirovic M , Pavlovic N , Music L , Bulatovic N , Boskovic A , Uiterwaal H , Bijsterveld N , De Groot J , Neefs J , van den Berg N , Piersma F , Wilde A , Hagens V , Van Es J , Van Opstal J , Van Rennes B , Verheij H , Breukers W , Tjeerdsma G , Nijmeijer R , Wegink D , Binnema R , Said S , Erküner Ö , Philippens S , van Doorn W , Crijns H , Szili-Torok T , Bhagwandien R , Janse P , Muskens A , van Eck M , Gevers R , van der Ven N , Duygun A , Rahel B , Meeder J , Vold A , Hansen C Holst , Engset I , Atar D , Dyduch-Fejklowicz B , Koba E , Cichocka M , Sokal A , Kubicius A , Pruchniewicz E , Kowalik-Sztylc A , Czapla W , Mróz I , Kozlowski M , Pawlowski T , Tendera M , Winiarska-Filipek A , Fidyk A , Slowikowski A , Haberka M , Lachor-Broda M , Biedron M , Gasior Z , Kołodziej M , Janion M , Gorczyca-Michta I , Wozakowska-Kaplon B , Stasiak M , Jakubowski P , Ciurus T , Drozdz J , Simiera M , Zajac P , Wcislo T , Zycinski P , Kasprzak J , Olejnik A , Harc-Dyl E , Miarka J , Pasieka M , Ziemińska-Łuć M , Bujak W , Śliwiński A , Grech A , Morka J , Petrykowska K , Prasał M , Hordyński G , Feusette P , Lipski P , Wester A , Streb W , Romanek J , Woźniak P , Chlebuś M , Szafarz P , Stanik W , Zakrzewski M , Kaźmierczak J , Przybylska A , Skorek E , Błaszczyk H , Stępień M , Szabowski S , Krysiak W , Szymańska M , Karasiński J , Blicharz J , Skura M , Hałas K , Michalczyk L , Orski Z , Krzyżanowski K , Skrobowski A , Zieliński L , Tomaszewska-Kiecana M , Dłużniewski M , Kiliszek M , Peller M , Budnik M , Balsam P , Opolski G , Tymińska A , Ozierański K , Wancerz A , Borowiec A , Majos E , Dabrowski R , Szwed H , Musialik-Lydka A , Leopold-Jadczyk A , Jedrzejczyk-Patej E , Koziel M , Lenarczyk R , Mazurek M , Kalarus Z , Krzemien-Wolska K , Starosta P , Nowalany-Kozielska E , Orzechowska A , Szpot M , Staszel M , Almeida S , Pereira H , Brandão Alves L , Miranda R , Ribeiro L , Costa F , Morgado F , Carmo P , Galvao Santos P , Bernardo R , Adragão P , Ferreira da Silva G , Peres M , Alves M , Leal M , Cordeiro A , Magalhães P , Fontes P , Leão S , Delgado A , Costa A , Marmelo B , Rodrigues B , Moreira D , Santos J , Santos L , Terchet A , Darabantiu D , Mercea S , Turcin Halka V , Pop Moldovan A , Gabor A , Doka B , Catanescu G , Rus H , Oboroceanu L , Bobescu E , Popescu R , Dan A , Buzea A , Daha I , Dan G , Neuhoff I , Baluta M , Ploesteanu R , Dumitrache N , Vintila M , Daraban A , Japie C , Badila E , Tewelde H , Hostiuc M , Frunza S , Tintea E , Bartos D , Ciobanu A , Popescu I , Toma N , Gherghinescu C , Cretu D , Patrascu N , Stoicescu C , Udroiu C , Bicescu G , Vintila V , Vinereanu D , Cinteza M , Rimbas R , Grecu M , Cozma A , Boros F , Ille M , Tica O , Tor R , Corina A , Jeewooth A , Maria B , Georgiana C , Natalia C , Alin D , Dinu-Andrei D , Livia M , Daniela R , Larisa R , Umaar S , Tamara T , Ioachim Popescu M , Nistor D , Sus I , Coborosanu O , Alina-Ramona N , Dan R , Petrescu L , Ionescu G , Popescu I , Vacarescu C , Goanta E , Mangea M , Ionac A , Mornos C , Cozma D , Pescariu S , Solodovnicova E , Soldatova I , Shutova J , Tjuleneva L , Zubova T , Uskov V , Obukhov D , Rusanova G , Soldatova I , Isakova N , Odinsova S , Arhipova T , Kazakevich E , Serdechnaya E , Zavyalova O , Novikova T , Riabaia I , Zhigalov S , Drozdova E , Luchkina I , Monogarova Y , Hegya D , Rodionova L , Rodionova L , Nevzorova V , Soldatova I , Lusanova O , Arandjelovic A , Toncev D , Vukmirovic L , Radisavljevic M , Milanov M , Sekularac N , Zdravkovic M , Hinic S , Dimkovic S , Acimovic T , Saric J , Radovanovic S , Kocijancic A , Obrenovic-Kircanski B , Kalimanovska Ostric D , Simic D , Jovanovic I , Petrovic I , Polovina M , Vukicevic M , Tomasevic M , Mujovic N , Radivojevic N , Petrovic O , Aleksandric S , Kovacevic V , Mijatovic Z , Ivanovic B , Tesic M , Potpara T , Ristic A , Vujisic-Tesic B , Nedeljkovic M , Karadzic A , Uscumlic A , Prodanovic M , Zlatar M , Asanin M , Bisenic B , Vasic V , Popovic Z , Djikic D , Sipic M , Peric V , Dejanovic B , Milosevic N , Backovic S , Stevanovic A , Andric A , Pencic B , Pavlovic-Kleut M , Celic V , Pavlovic M , Petrovic M , Vuleta M , Petrovic N , Simovic S , Savovic Z , Milanov S , Davidovic G , Iric-Cupic V , Djordjevic D , Damjanovic M , Zdravkovic S , Topic V , Stanojevic D , Randjelovic M , Jankovic-Tomasevic R , Atanaskovic V , Antic S , Pavlovic M , Simonovic D , Stojanovic M , Stojanovic S , Mitic V , Ilic V , Petrovic D , Deljanin Ilic M , Ilic S , Stoickov V , Markovic S , Mijatovic A , Tanasic D , Petrovic D , Radakovic G , Peranovic J , Pavlovic M , Panic-Jelic N , Vujadinovic O , Pajic P , Bekic S , Kovacevic S , García Fernandez A , Perez Cabeza A , Anguita M , Tercedor Sanchez L , Mau E , Loayssa J , Ayarra M , Carpintero M , Roldán Rabadan I , Leal M , Gil Ortega M , Tello Montoliu A , Orenes Piñero E , Manzano Fernández S , Marín F , Romero Aniorte A , Veliz Martínez A , Quintana Giner M , Ballesteros G , Palacio M , Alcalde O , García-Bolao I , Bertomeu Gonzalez V , Otero-Raviña F , García Seara J , Gonzalez Juanatey J , Dayal N , Maziarski P , Gentil-Baron P , Shah D , Koç M , Onrat E , Dural I E , Yilmaz K , Özin B , Tan Kurklu S , Atmaca Y , Canpolat U , Tokgozoglu L , Dolu A K , Demirtas B , Sahin D , Ozcan Celebi O , Diker E , Gagirci G , Turk U O , Ari H , Polat N , Toprak N , Sucu M , Akin Serdar O , Taha Alper A , Kepez A , Yuksel Y , Uzunselvi A , Yuksel S , Sahin M , Kayapinar O , Ozcan T , Kaya H , Yilmaz M B , Kutlu M , Demir M , Gibbs C , Kaminskiene S , Bryce M , Skinner A , Belcher G , Hunt J , Stancombe L , Holbrook B , Peters C , Tettersell S , Shantsila A , Lane D , Senoo K , Proietti M , Russell K , Domingos P , Hussain S , Partridge J , Haynes R , Bahadur S , Brown R , McMahon S , Lip G Y H , McDonald J , Balachandran K , Singh R , Garg S , Desai H , Davies K , Goddard W , Galasko G , Rahman I , Chua Y , Payne O , Preston S , Brennan O , Pedley L , Whiteside C , Dickinson C , Brown J , Jones K , Benham L , Brady R , Buchanan L , Ashton A , Crowther H , Fairlamb H , Thornthwaite S , Relph C , McSkeane A , Poultney U , Kelsall N , Rice P , Wilson T , Wrigley M , Kaba R , Patel T , Young E , Law J , Runnett C , Thomas H , McKie H , Fuller J , Pick S , Sharp A , Hunt A , Thorpe K , Hardman C , Cusack E , Adams L , Hough M , Keenan S , Bowring A , Watts J , Zaman J , Goffin K , Nutt H , Beerachee Y , Featherstone J , Mills C , Pearson J , Stephenson L , Grant S , Wilson A , Hawksworth C , Alam I , Robinson M , Ryan S , Egdell R , Gibson E , Holland M , Leonard D , Mishra B , Ahmad S , Randall H , Hill J , Reid L , George M , McKinley S , Brockway L , Milligan W , Sobolewska J , Muir J , Tuckis L , Winstanley L , Jacob P , Kaye S , Morby L , Jan A , Sewell T , Boos C , Wadams B , Cope C , Jefferey P , Andrews N , Getty A , Suttling A , Turner C , Hudson K , Austin R , Howe S , Iqbal R , Gandhi N , Brophy K , Mirza P , Willard E , Collins S , Ndlovu N , Subkovas E , Karthikeyan V , Waggett L , Wood A , Bolger A , Stockport J , Evans L , Harman E , Starling J , Williams L , Saul V , Sinha M , Bell L , Tudgay S , Kemp S , Brown J , Frost L , Ingram T , Loughlin A , Adams C , Adams M , Hurford F , Owen C , Miller C , Donaldson D , Tivenan H , Button H , Nasser A , Jhagra O , Stidolph B , Brown C , Livingstone C , Duffy M , Madgwick P , Roberts P , Greenwood E , Fletcher L , Beveridge M , Earles S , McKenzie D , Beacock D , Dayer M , Seddon M , Greenwell D , Luxton F , Venn F , Mills H , Rewbury J , James K , Roberts K , Tonks L , Felmeden D , Taggu W , Summerhayes A , Hughes D , Sutton J , Felmeden L , Khan M , Walker E , Norris L , O'Donohoe L , Mozid A , Dymond H , Lloyd-Jones H , Saunders G , Simmons D , Coles D , Cotterill D , Beech S , Kidd S , Wrigley B , Petkar S , Smallwood A , Jones R , Radford E , Milgate S , Metherell S , Cottam V , Buckley C , Broadley A , Wood D , Allison J , Rennie K , Balian L , Howard L , Pippard L , Board S , Pitt-Kerby T 
Published: October 2021

Aims

The safety of digoxin therapy in atrial fibrillation (AF) remains ill-defined. We aimed to evaluate the effects of digoxin over beta-blocker therapy in AF.

Methods and results

Patients with AF who were treated with either digoxin or a beta blocker from the ESC–EHRA EORP AF (European Society of Cardiology–European Heart Rhythm Association EURObservational Research Programme Atrial Fibrillation) General Long-Term Registry were included. Outcomes of interest were all-cause mortality, cardiovascular (CV) mortality, non-CV mortality, quality of life, and number of patients with unplanned hospitalizations. Of 6377 patients, 549 (8.6%) were treated with digoxin. Over 24 months, there were 550 (8.6%) all-cause mortality events and 1304 (23.6%) patients with unplanned emergency hospitalizations. Compared to beta blocker, digoxin therapy was associated with increased all-cause mortality [hazard ratio (HR) 1.90 (95% confidence interval, CI, 1.48–2.44)], CV mortality [HR 2.18 (95% CI 1.47–3.21)], and non-CV mortality [HR 1.68 (95% CI 1.02–2.75)] with reduced quality of life [health utility score 0.555 (±0.406) vs. 0.705 (±0.346), P &lt; 0.001] but no differences in emergency hospitalizations [HR 1.00 (95% CI 0.56–1.80)] or AF-related hospitalizations [HR 0.95 (95% CI 0.60–1.52)]. On multivariable analysis, there were no differences in any of the outcomes between both groups, after accounting for potential confounders. Similar results were obtained in the subgroups of patients with permanent AF and coexisting heart failure. There were no differences in outcomes between AF patients receiving digoxin with and without chronic kidney disease.

Conclusion

Poor outcomes related to the use of digoxin over beta-blocker therapy in terms of excess mortality and reduced quality of life are associated with the presence of other risk factors rather than digoxin per se. The choice of digoxin or beta-blocker therapy had no influence on the incidence of unplanned hospitalizations.