Comparative effectiveness and safety of non-vitamin K antagonists for atrial fibrillation in clinical practice: GLORIA-AF Registry
Authors: Lip Gregory Y. H. , Kotalczyk Agnieszka , Teutsch Christine , Diener Hans-Christoph , Dubner Sergio J. , Halperin Jonathan L. , Ma Chang-Sheng , Rothman Kenneth J. , Marler Sabrina , Gurusamy Venkatesh Kumar , Huisman Menno V. ,   for the GLORIA-AF Investigators, Abban Dzifa Wosornu , Aziz Emad , Kalan Marica Bracic , Abdul Nasser , Backes Luciano Marcelo , Bradman Drew , Abud Atilio Marcelo , Badings E. , Brautigam Donald , Adams Fran , Bagni Ermentina , Breton Nicolas , Addala Srinivas , Baker Seth H. , Brouwers P. J. A. M. , Adragão Pedro , Bala Richard , Browne Kevin , Ageno Walter , Baldi Antonio , Cortada Jordi Bruguera , Aggarwal Rajesh , Bando Shigenobu , Bruni A. , Agosti Sergio , Banerjee Subhash , Brunschwig Claude , Agostoni Piergiuseppe , Bank Alan , Buathier Hervé , Aguilar Francisco , Esquivias Gonzalo Barón , Buhl Aurélie , Linares Julio Aguilar , Barr Craig , Bullinga John , Aguinaga Luis , Bartlett Maria , Cabrera Jose Walter , Ahmed Jameel , Basic Kes Vanja , Caccavo Alberto , Aiello Allessandro , Baula Giovanni , Cai Shanglang , Ainsworth Paul , Behrens Steffen , Caine Sarah , Aiub Jorge Roberto , Bell Alan , Calò Leonardo , Al-Dallow Raed , Benedetti Raffaella , Calvi Valeria , Alderson Lisa , Mazuecos Juan Benezet , Sánchez Mauricio Camarillo , Velasco Jorge Antonio Aldrete , Benhalima Bouziane , Candeias Rui , Alexopoulos Dimitrios , Bergler-Klein Jutta , Capuano Vincenzo , Manterola Fernando Alfonso , Berneau Jean-Baptiste , Capucci Alessandro , Aliyar Pareed , Bernstein Richard A. , Caputo Ronald , Alonso David , Berrospi Percy , Rizo Tatiana Cárdenas , da Costa Fernando Augusto Alves , Berti Sergio , Cardona Francisco , Amado José , Berz Andrea , da Costa Darrieux Francisco Carlos , Amara Walid , Best Elizabeth , Vera Yan Carlos Duarte , Amelot Mathieu , Bettencourt Paulo , Carolei Antonio , Amjadi Nima , Betzu Robert , Carreño Susana , Ammirati Fabrizio , Bhagwat Ravi , Carvalho Paula , Andrade Marianna , Bhatta Luna , Cary Susanna , Andrawis Nabil , Biscione Francesco , Casu Gavino , Annoni Giorgio , Bisignani Giovanni , Cavallini Claudio , Ansalone Gerardo , Black Toby , Cayla Guillaume , Ariani M. Kevin , Bloch Michael J. , Celentano Aldo , Arias Juan Carlos , Bloom Stephen , Cha Tae-Joon , Armero Sébastien , Blumberg Edwin , Cha Kwang Soo , Arora Chander , Bo Mario , Chae Jei Keon , Aslam Muhammad Shakil , Bøhmer Ellen , Chalamidas Kathrine , Asselman M. , Bollmann Andreas , Challappa Krishnan , Audouin Philippe , Bongiorni Maria Grazia , Chand Sunil Prakash , Augenbraun Charles , Boriani Giuseppe , Chandrashekar Harinath , Aydin S. , Boswijk D. J. , Chartier Ludovic , Aydin S. , Bott Jochen , Chatterjee Kausik , Ayryanova Ivaneta , Bottacchi Edo , Ayala Carlos Antero Chavez , Cheema Aamir , Davis Gershan , Evonich Rudolph , Cheema Amjad , Davy Jean-Marc , Evseeva Oksana , Chen Lin , Dayer Mark , Ezhov Andrey , Chen Shih-Ann , De Biasio Marzia , Fahmy Raed , Chen Jyh Hong , De Bonis Silvana , Fang Quan , Chiang Fu-Tien , De Caterina Raffaele , Farsad Ramin , Chiarella Francesco , De Franceschi Teresiano , Fauchier Laurent , Chih-Chan Lin , de Groot J. R. , Favale Stefano , Cho Yong Keun , De Horta José , Fayard Maxime , Choi Jong-Il , De La Briolle Axel , Fedele Jose Luis , Choi Dong Ju , de la Pena Topete Gilberto , Fedele Francesco , Chouinard Guy , de Paola Angelo Amato Vicenzo , Fedorishina Olga , Chow Danny Hoi-Fan , de Souza Weimar , Fera Steven R. , Chrysos Dimitrios , de Veer A. , Ferreira Luis Gustavo Gomes , Chumakova Galina , De Wolf Luc , Ferreira Jorge , Valenzuela Eduardo Julián José Roberto Chuquiu , Decoulx Eric , Ferri Claudio , Nica Nicoleta Cindea , Deepak Sasalu , Ferrier Anna , Cislowski David J. , Defaye Pascal , Ferro Hugo , Clay Anthony , Munoz Freddy Del-Carpio , Finsen Alexandra , Clifford Piers , Brkljacic Diana Delic , First Brian , Cohen Andrew , Deumite N. Joseph , Fischer Stuart , Cohen Michael , Di Legge Silvia , Fonseca Catarina , Cohen Serge , Diemberger Igor , Almeida Luísa Fonseca , Colivicchi Furio , Dietz Denise , Forman Steven , Collins Ronan , Dionísio Pedro , Frandsen Brad , Colonna Paolo , Dong Qiang , French William , Compton Steve , dos Santos Fabio Rossi , Friedman Keith , Connolly Derek , Dotcheva Elena , Friese Athena , Conti Alberto , Doukky Rami , Fruntelata Ana Gabriela , Buenostro Gabriel Contreras , D’Souza Anthony , Fujii Shigeru , Coodley Gregg , Dubrey Simon , Fumagalli Stefano , Cooper Martin , Ducrocq Xavier , Fundamenski Marta , Coronel Julian , Dupljakov Dmitry , Furukawa Yutaka , Corso Giovanni , Duque Mauricio , Gabelmann Matthias , Sales Juan Cosín , Dutta Dipankar , Gabra Nashwa , Cottin Yves , Duvilla Nathalie , Gadsbøll Niels , Covalesky John , Duygun A. , Galinier Michel , Cracan Aurel , Dziewas Rainer , Gammelgaard Anders , Crea Filippo , Eaton Charles B. , Ganeshkumar Priya , Crean Peter , Eaves William , Gans Christopher , Crenshaw James , Ebels-Tuinbeek L. A. , Quintana Antonio Garcia , Cullen Tina , Ehrlich Clifford , Gartenlaub Olivier , Darius Harald , Eichinger-Hasenauer Sabine , Gaspardone Achille , Dary Patrick , Eisenberg Steven J. , Genz Conrad , Dascotte Olivier , Jabali Adnan El , Georger Frédéric , Dauber Ira , Shahawy Mahfouz El , Georges Jean-Louis , Davalos Vicente , Hernandes Mauro Esteves , Georgeson Steven , Davies Ruth , Izal Ana Etxeberria , Giedrimas Evaldas , Gierba Mariusz , Haruna Tetsuya , Jarmukli Nabil , Ortega Ignacio Gil , Hayek Emil , Jeanfreau Robert J. , Gillespie Eve , Healey Jeff , Jenkins Ronald D. , Giniger Alberto , Hearne Steven , Sánchez Carlos Jerjes , Giudici Michael C. , Heffernan Michael , Jimenez Javier , Gkotsis Alexandros , Heggelund Geir , Jobe Robert , Glotzer Taya V. , Heijmeriks J. A. , Joen-Jakobsen Tomas , Gmehling Joachim , Hemels Maarten , Jones Nicholas , Gniot Jacek , Hendriks I. , Jorge Jose Carlos Moura , Goethals Peter , Henein Sam , Jouve Bernard , Goldbarg Seth , Her Sung-Ho , Jung Byung Chun , Goldberg Ronald , Hermany Paul , Jung Kyung Tae , Goldmann Britta , Del Río Jorge Eduardo Hernández , Jung Werner , Golitsyn Sergey , Higashino Yorihiko , Kachkovskiy Mikhail , Gómez Silvia , Hill Michael , Kafkala Krystallenia , Mesa Juan Gomez , Hisadome Tetsuo , Kalinina Larisa , Gonzalez Vicente Bertomeu , Hishida Eiji , Kallmünzer Bernd , Hermosillo Jesus Antonio Gonzalez , Hoffer Etienne , Kamali Farzan , López Víctor Manuel González , Hoghton Matthew , Kamo Takehiro , Gorka Hervé , Hong Kui , Kampus Priit , Gornick Charles , Hong Suk keun , Kashou Hisham , Gorog Diana , Horbach Stevie , Kastrup Andreas , Gottipaty Venkat , Horiuchi Masataka , Katsivas Apostolos , Goube Pascal , Hou Yinglong , Kaufman Elizabeth , Goudevenos Ioannis , Hsing Jeff , Kawai Kazuya , Graham Brett , Huang Chi-Hung , Kawajiri Kenji , Greer G. Stephen , Huckins David , Kazmierski John F. , Gremmler Uwe , Hughes Kathy , Keeling P. , Grena Paul G. , Huizinga A. , Saraiva José Francisco Kerr , Grond Martin , Hulsman E. L. , Ketova Galina , Gronda Edoardo , Hung Kuo-Chun , Khaira AJIT Singh , Grönefeld Gerian , Hwang Gyo-Seung , Khripun Aleksey , Gu Xiang , Ikpoh Margaret , Kim Doo-Il , Torres Ivett Guadalupe Torres , Imberti Davide , Kim Young Hoon , Guardigli Gabriele , Ince Hüseyin , Kim Nam Ho , Guevara Carolina , Indolfi Ciro , Kim Dae Kyeong , Guignier Alexandre , Inoue Shujiro , Kim Jeong Su , Gulizia Michele , Irles Didier , Kim June Soo , Gumbley Michael , Iseki Harukazu , Kim Ki Seok , Günther Albrecht , Israel C. Noah , Kim Jin bae , Ha Andrew , Iteld Bruce , Kinova Elena , Hahalis Georgios , Iyer Venkat , Klein Alexander , Hakas Joseph , Jackson-Voyzey Ewart , Kmetzo James J. , Hall Christian , Jaffrani Naseem , Kneller G. Larsen , Han Bing , Jäger Frank , Knezevic Aleksandar , Han Seongwook , James Martin , Koh Su Mei Angela , Hargrove Joe , Jang Sung-Won , Koide Shunichi , Hargroves David , Jaramillo Nicolas , Kollias Anastasios , Kooistra J. A. , Li Weihua , McClure John , Koons Jay , Li Xiaoming , McCormack Terry , Koschutnik Martin , Lichy Christhoh , McGarity William , Kostis William J. , Lieber Ira , McIntyre Hugh , Kovacic Dragan , Rodriguez Ramon Horacio Limon , McLaurin Brent , Kowalczyk Jacek , Lin Hailong , Alvaro Feliz , Palomino Medina , Koziolova Natalya , Lip Gregory Y. H. , Melandri Francesco , Kraft Peter , Liu Feng , Meno Hiroshi , Kragten Johannes A. , Liu Hengliang , Menzies Dhananjai , Krantz Mori , Esperon Guillermo Llamas , Mercader Marco , Krause Lars , Navarro Nassip Llerena , Meyer Christian , Krenning B. J. , Lo Eric , Meyer Beat J. , Krikke F. , Lokshyn Sergiy , Miarka Jacek , Kromhout Z. , López Amador , Mibach Frank , Krysiak Waldemar , López-Sendón José Luís , Michalski Dominik , Kumar Priya , Filho Adalberto Menezes Lorga , Michel Patrik , Kümler Thomas , Lorraine Richard S. , Chreih Rami Mihail , Kuniss Malte , Luengas Carlos Alberto , Luengas Alberto , Mikdadi Ghiath , Kuo Jen-Yuan , Luke Robert , Mikus Milan , Küppers Achim , Luo Ming , Milicic Davor , Kurrelmeyer Karla , Lupovitch Steven , Militaru Constantin , Kwak Choong Hwan , Lyrer Philippe , Minaie Sedi , Laboulle Bénédicte , Ma Changsheng , Minescu Bogdan , Labovitz Arthur , Ma Genshan , Mintale Iveta , Ter Lai Wen , Madariaga Irene , Mirault Tristan , Lam Andy , Maeno Koji , Mirro Michael J. , Lam Yat Yin , Magnin Dominique , Mistry Dinesh , Lanas Zanetti Fernando , Maid Gustavo , Miu Nicoleta Violeta , Landau Charles , Mainigi Sumeet K. , Miyamoto Naomasa , Landini Giancarlo , Makaritsis Konstantinos , Moccetti Tiziano , Lanna Figueiredo Estêvão , Malhotra Rohit , Mohammed Akber , Larsen Torben , Manning Rickey , Nor Azlisham Mohd , Lavandier Karine , Manolis Athanasios , Mollerus Michael , LeBlanc Jessica , Hurtado Helard Andres Manrique , Molon Giulio , Lee Moon Hyoung , Mantas Ioannis , Mondillo Sergio , Lee Chang-Hoon , Jattin Fernando Manzur , Moniz Patrícia , Lehman John , Maqueda Vicky , Mont Lluis , Leitão Ana , Marchionni Niccolo , Montagud Vicente , Lellouche Nicolas , Ortuno Francisco Marin , Montaña Oscar , Lelonek Malgorzata , Santana Antonio Martín , Monti Cristina , Lenarczyk Radoslaw , Martinez Jorge , Moretti Luciano , Lenderink T. , Maskova Petra , Mori Kiyoo , González Salvador León , Hernandez Norberto Matadamas , Moriarty Andrew , Leong-Sit Peter , Matsuda Katsuhiro , Morka Jacek , Leschke Matthias , Maurer Tillmann , Moschini Luigi , Ley Nicolas , Mauro Ciro , Moschos Nikitas , Li Zhanquan , May Erik , Mügge Andreas , Li Xiaodong , Mayer Nolan , Mulhearn Thomas J. , Muresan Carmen , Jose Eena Padayattil , Précoma Dalton Bertolim , Muriago Michela , Padilla Francisco Gerardo Padilla , Prelle Alessandro , Musial Wlodzimierz , Rios Victoria Padilla , Prodafikas John , Musser Carl W. , Pajes Giuseppe , Protasov Konstantin , Musumeci Francesco , Pandey A. Shekhar , Pye Maurice , Nageh Thuraia , Paparella Gaetano , Qiu Zhaohui , Nakagawa Hidemitsu , Paris F. , Quedillac Jean-Michel , Nakamura Yuichiro , Park Hyung Wook , Raev Dimitar , Nakayama Toru , Park Jong Sung , Grado Carlos Antonio Raffo , Nam Gi-Byoung , Parthenakis Fragkiskos , Rahimi Sidiqullah , Nanna Michele , Passamonti Enrico , Raisaro Arturo , Natarajan Indira , Patel Rajesh J. , Rama Bhola , Nayak Hemal M. , Patel Jaydutt , Ramos Ricardo , Naydenov Stefan , Patel Mehool , Ranieri Maria , Nazlić Jurica , Patrick Janice , Raposo Nuno , Nechita Alexandru Cristian , Jimenez Ricardo Pavón , Rashba Eric , Nechvatal Libor , Paz Analía , Rauch-Kroehnert Ursula , Negron Sandra Adela , Pengo Vittorio , Reddy Ramakota , Neiman James , Pentz William , Renda Giulia , Neuenschwander Fernando Carvalho , Pérez Beatriz , Reza Shabbir , Neves David , Ríos Alma Minerva Pérez , Ria Luigi , Neykova Anna , Pérez-Cabezas Alejandro , Richter Dimitrios , Miguel Ricardo Nicolás , Perlman Richard , Rickli Hans , Nijmeh George , Persic Viktor , Rieker Werner , Nizov Alexey , Perticone Francesco , Vera Tomas Ripolil , Campos Rodrigo Noronha , Peters Terri K. , Ritt Luiz Eduardo , Nossan Janko , Petkar Sanjiv , Roberts Douglas , Novikova Tatiana , Pezo Luis Felipe , Briones Ignacio Rodriguez , Nowalany-Kozielska Ewa , Pflücke Christian , Escudero Aldo Edwin Rodriguez , Nsah Emmanuel , Pham David N. , Pascual Carlos Rodríguez , Fragoso Juan Carlos Nunez , Phillips Roland T. , Roman Mark , Nurgalieva Svetlana , Phlaum Stephen , Romeo Francesco , Nuyens Dieter , Pieters Denis , Ronner E. , Nyvad Ole , Pineau Julien , Roux Jean-Francois , de Los Rios Ibarra Manuel Odin , Pinter Arnold , Rozkova Nadezda , O’Donnell Philip , Pinto Fausto , Rubacek Miroslav , O’Donnell Martin , Pisters R. , Rubalcava Frank , Oh Seil , Pivac Nediljko , Russo Andrea M. , Oh Yong Seog , Pocanic Darko , Rutgers Matthieu Pierre , Oh Dongjin , Podoleanu Cristian , Rybak Karin , O‘Hara Gilles , Politano Alessandro , Said Samir , Oikonomou Kostas , Poljakovic Zdravka , Sakamoto Tamotsu , Olivares Claudia , Pollock Stewart , Salacata Abraham , Oliver Richard , Garcéa Jose Polo , Salem Adrien , Ruiz Rafael Olvera , Poppert Holger , Bodes Rafael Salguero , Olympios Christoforos , Porcu Maurizio , Saltzman Marco A. , Omaszuk-Kazberuk Anna , Reino Antonio Pose , Salvioni Alessandro , Asensi Joaquín Osca , Prasad Neeraj , Vallejo Gregorio Sanchez , Fernández Marcelo Sanmartín , Sokal Adam , Tu Tian Ming , Saporito Wladmir Faustino , Yan Yannie Soo Oi , Tuininga Ype , Sarikonda Kesari , Sotolongo Rodolfo , Turakhia Minang , Sasaoka Taishi , de Souza Olga Ferreira , Turk Samir , Sati Hamdi , Sparby Jon Arne , Turner Wayne , Savelieva Irina , Spinar Jindrich , Tveit Arnljot , Scala Pierre-Jean , Sprigings David , Tytus Richard , Schellinger Peter , Spyropoulos Alex C. , Valadão C. , Scherr Carlos , Stakos Dimitrios , van Bergen P. F. M. M. , Schmitz Lisa , Steinwender Clemens , van de Borne Philippe , Schmitz Karl-Heinz , Stergiou Georgios , van den Berg B. J. , Schmitz Bettina , Stiell Ian , van der Zwaan C. , Schnabel Teresa , Stoddard Marcus , Van Eck M. , Schnupp Steffen , Stoikov Anastas , Vanacker Peter , Schoeniger Peter , Streb Witold , Vasilev Dimo , Schön Norbert , Styliadis Ioannis , Vasilikos Vasileios , Schwimmbeck Peter , Su Guohai , Vasilyev Maxim , Seamark Clare , Su Xi , Veerareddy Srikar , Searles Greg , Sudnik Wanda , Miño Mario Vega , Seidl Karl-Heinz , Sukles Kai , Venkataraman Asok , Seidman Barry , Sun Xiaofei , Verdecchia Paolo , Sek Jaroslaw , Swart H. , Versaci Francesco , Sekaran Lakshmanan , Szavits-Nossan Janko , Vester Ernst Günter , Serrati Carlo , Taggeselle Jens , Vial Hubert , Shah Neerav , Takagi Yuichiro , Victory Jason , Shah Vinay , Takhar Amrit Pal Singh , Villamil Alejandro , Shah Anil , Tamm Angelika , Vincent Marc , Shah Shujahat , Tanaka Katsumi , Vlastaris Anthony , Sharma Vijay Kumar , Tanawuttiwat Tanyanan , Dahl Jürgen vom , Shaw Louise , Tang Sherman , Vora Kishor , Sheikh Khalid H. , Tang Aylmer , Vranian Robert B. , Shimizu Naruhito , Tarsi Giovanni , Wakefield Paul , Shimomura Hideki , Tassinari Tiziana , Wang Ningfu , Shin Dong-Gu , Tayal Ashis , Wang Mingsheng , Shin Eun-Seok , Tayebjee Muzahir , Wang Xinhua , Shite Junya , Berg J. M. ten , Wang Feng , Sibilio Gerolamo , Tesloianu Dan , Wang Tian , Silver Frank , The Salem H. K. , Warner Alberta L. , Sime Iveta , Thomas Dierk , Watanabe Kouki , Simmers Tim A. , Timsit Serge , Wei Jeanne , Singh Narendra , Tobaru Tetsuya , Weimar Christian , Siostrzonek Peter , Tomasik. Andrzej R. , Weiner Stanislav , Smadja Didier , Torosoff Mikhail , Weinrich Renate , Smith David W. , Touze Emmanuel , Wen Ming-Shien , Snitman Marcelo , Trendafilova Elina , Wiemer Marcus , Filho Dario Sobral , Tsai W. Kevin , Wiggers Preben , Soda Hassan , Tse Hung Fat , Wilke Andreas , Sofley Carl , Tsutsui Hiroshi , Williams David , Williams Marcus L. , Yan Ping Yen Bryan , Zhang Ping , Witzenbichler Bernhard , Yang Tianlun , Zhang Jun , Wong Brian , Yao Jing , Zhao Shui Ping , Wong Ka Sing Lawrence , Yeh Kuo-Ho , Zhao Yujie , Wozakowska-Kaplon Beata , Yin Wei Hsian , Zhao Zhichen , Wu Shulin , Yotov Yoto , Zheng Yang , Wu Richard C. , Zahn Ralf , Zhou Jing , Wunderlich Silke , Zarich Stuart , Zimmermann Sergio , Wyatt Nell , Zenin Sergei , Zini Andrea , Wylie John , Zeuthen Elisabeth Louise , Zizzo Steven , Xu Yong , Zhang Huanyi , Zong Wenxia , Xu Xiangdong , Zhang Donghui , Zukerman LSteven , Yamanoue Hiroki , Zhang Xingwei , Yamashita Takeshi 
Published: March 2022

Background and purpose

Prospectively collected data comparing the safety and effectiveness of individual non-vitamin K antagonists (NOACs) are lacking. Our objective was to directly compare the effectiveness and safety of NOACs in patients with newly diagnosed atrial fibrillation (AF).

Methods

In GLORIA-AF, a large, prospective, global registry program, consecutive patients with newly diagnosed AF were followed for 3 years. The comparative analyses for (1) dabigatran vs rivaroxaban or apixaban and (2) rivaroxaban vs apixaban were performed on propensity score (PS)-matched patient sets. Proportional hazards regression was used to estimate hazard ratios (HRs) for outcomes of interest.

Results

The GLORIA-AF Phase III registry enrolled 21,300 patients between January 2014 and December 2016. Of these, 3839 were prescribed dabigatran, 4015 rivaroxaban and 4505 apixaban, with median ages of 71.0, 71.0, and 73.0 years, respectively. In the PS-matched set, the adjusted HRs and 95% confidence intervals (CIs) for dabigatran vs rivaroxaban were, for stroke: 1.27 (0.79–2.03), major bleeding 0.59 (0.40–0.88), myocardial infarction 0.68 (0.40–1.16), and all-cause death 0.86 (0.67–1.10). For the comparison of dabigatran vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 1.16 (0.76–1.78), myocardial infarction 0.84 (0.48–1.46), major bleeding 0.98 (0.63–1.52) and all-cause death 1.01 (0.79–1.29). For the comparison of rivaroxaban vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 0.78 (0.52–1.19), myocardial infarction 0.96 (0.63–1.45), major bleeding 1.54 (1.14–2.08), and all-cause death 0.97 (0.80–1.19).

Conclusions

Patients treated with dabigatran had a 41% lower risk of major bleeding compared with rivaroxaban, but similar risks of stroke, MI, and death. Relative to apixaban, patients treated with dabigatran had similar risks of stroke, major bleeding, MI, and death. Rivaroxaban relative to apixaban had increased risk for major bleeding, but similar risks for stroke, MI, and death.

Registration

URL:https://www.clinicaltrials.gov. Unique identifiers: NCT01468701, NCT01671007. Date of registration: September 2013.

Graphical abstract