Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone

6533b828fe1ef96bd128911e

RESEARCH PRODUCT

Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone

Da Stempel Ih Raphiou Km Kral Am Yeakey Ah Emmett Cm Prazma Ks Buaron Sj Pascoe Investigators Austri Hh Altieri Jd Antuni Ma Bergna Ja Cuadrado De Gennaro Ms Fazio Lizandrelo Cl G Gattolin Am Gosn Ld Larrateguy Am Marcipar Jf Maspero Iv Medina Perez Chada Rd D Silva Cf Victorio Pg Bardin Pa Carroll Bs Clements Nd Dore Pd Robinson Da Fitzgerald Pj Robinson Ma Russo D Sajkov Ps Thomas Jw Upham B Forstner G Kaik Gh Koeberl M Studnicka G Wallner Y Balthazar A Bauler Lj Dupont Jb Martinot V Ninane R Peché C Pilette R Dimitrova D Dimova G Kissyova Ibrishimova M Loboshka Becheva M Machkovska S Madjarov M Mandazhieva Pepelanova I Naidenova K Noleva N Takovska C Terziev Nk Aggarwal Kr Chapman Ma Csanadi R Dhillon S Henein Aj Kelly As Lam Jj Liem Md Lougheed Dw Lowe Q Rizvi L Van Den Berg B Zidel Barros Monge Mj Calvo Gil Ma Castillo Hofer Cr Diaz Amor Pv V Lezana Soya Quilodran Silva Cn F Bolivar Grimaldos I Solarte-rodriguez R Butkovic-tomljanovic M Hegedus-jungvirth I Ivkovic-jurekovic G Simunov-karuza M Buresova J Bursova J Fratrik E Guttlerova P Hartman I Jirmanova P Kalina P Kolman M Kucera L Povysilova P Pravda A Svabkova L Zakova V Backer N Maltbaek Cr Johnsen Sp Aries A Babyesiza D Barth A Benedix P Berg B Bergtholdt U Bettig Hw Bindig U Botzen R Brehler Go Breyer M Bruckhaus-walter T Dapper Jg Eckhard R Engelhard F Feldmeyer H Fissan Kh Franz Bs Frick J Funck Cm Gessner T Ginko Ce Grigat V Grimm-sachs G Groth J Hampf G Hanf G Havasi-jost Gu Heinz K Helm S Hoeltz S Hofmann R Jander M Jandl B Jasch-hoppe T Jung Jj Junggeburth P Kardos W Knueppel T Koch C Kolorz M Korduan B Korth-wiemann Hg Krezdorn A Kroker M Kruell P Kuehne U Lenk E Liefring J Merke L Micke W Mitlehner H Mueller If Naudts G Neumann W Oldenburg A Overlack F Panzer N Reinholz R Remppis P Riegel P Rueckert Rj Schaetzl U Schauer E Hamelmann I Schenkenberger V Schlegel G Scholz M Schroers A Schwittay M Sebert K Tyler Pa Soemantri P Stock G Stuchlik M Unland C Von Mallinckrodt J Wachter U Weber F Weberling S Wehgartner-winkler J Weimer S Wiemer Ej Winkelmann Kh Zeisler A Ziegner Hh Zimny Z Andrasofszky A Bartha M Farkas K Gömöri S Kis K Major I Mészáros M Mezei M Rakvacs Z Szalai J Szántó M Szentesi E Szolnoki E Valyon H Zibotics J Anwar C Arimah S Djajalaksana Ib Rai Ar Setijadi Db Setyanto F Susanti T Syafiuddin Ln Syamsi P Wijanarko F Yunus M Bonavia M Braga Aa Chetta I Cerveri M Luisetti N Crimi R Cutrera M De Rosa S Esposito A Foresi E Gammeri E Iemoli Dl Legnani G Michetti Ea Pastorello A Pesci M Pistolesi E Riva A Romano N Scichilone L Terracciano S Tripodi I Choi C Kim Js Kim Wj Kim Yy Koh Ss Kwon Sh Lee S Lee Sk Lee Cs Park I Cirule R Eglite I Petrova M Poga I Smiltena A Chomiciene I Davoliene V Griskeviciene A Naudziunas S Naudziunas O Rudzeviciene B Sitkauskiene G Urbonas D Vaicius A Valavicius A Valiulis J Vebriene Bin Abdul Aziz Fa M Daud Ai Ismail Tengku Saifudin Ti Md Kassim Rm Mohd Fadzli Fb Wan Mohamad Wh Aguilar Dominguez Pe Ra Aguilar-orozco S Garza-salinas Sp Ramirez-diaz F Sánchez Llamas M Soto-ramos Hj Velarde-mora I Aguirre Sosa Am Cisneros Estrella Viladegut Ra A Matsuno Fuchigami Tt Adiaz-baui Ap Bernan Af Onia Mj Sandagon S S-naval Cy Yu Z Bartuzi A Bielous-wilk Ł Błażowski A Bożek J Brzostek J Chorostowska-wynimko K Ciekalska D Ziora J Cieslicki A Emeryk K Folcik A Gałuszka-bilińska R Gawlik M Giejlo R Harat T Hofman K Jahnz-różyk M Jedrzejczak T Kachel D Kamiński A Kelm Warchol Z Konieczny A Kwasniewski W Leszczyński G Mincewicz K Niezgoda A Olszewska-ziąber M Onasz-manitius M Pawlukiewicz P Piotrowicz W Piotrowski E Pisarczyk-bogacka P Piskorz A Prokop-staszecka A Roslan A Słomka E Smalera I Stelmach M Swierczynska-krepa M Szmidt M Tarnowska-matusiak B Tłuczykont K Tyminska J Waszkuc-golonko I Wojciechowska Ds Alexandrescu Ml Neamtu D Todea E Alekseeva E Aleksandrova I Asherova Ol Barbarash O Bugrova Eb Bukreeva A Chermenskiy O Chizhova I Demko A Evdokimova Ml Giorgadze S Grigoryev I Irkhina Nv Khurkhurova Eg Kondyurina Vi Kostin L Kudelya Sl Laleko L Lenskaya S Levashov N Logvinenko A Martynov Y Mizernitski B Nemtsov Vg Novozhenov S Pavlishchuk Vv Popova Ov Reshetko A Sherenkov Vs Shirinsky L Shpagina Ki Soloviev A Tkachev Vi Trofimov Al Vertkin E Vorobeva E Idrisova S Yakushin V Zadionchenko O Zhiglinskaya K Zykov V Dopudja Pantic R Nadaskic B Nestorovic V Skodric Trifunovic A Stojanovic M Vukcevic T Vujic M Mitic Milikic P Banovcin H Horvathova P Sr Karako J Plutinsky E Pribulova M Szarazova A Zlatos L Adams A Badat A Bassa J Breedt A Bruning Gc Ellis S Emanuel Lf Fouche Ma Fulat M Gani Ms Ismail Jc Jurgens H Nell G Nieuwoudt F Noor Ct Bolliger As Puterman N Siddique Js Trokis Ya Vahed Van Der Berg Bj M Van Der Linden L Van Zyl Ss Visser I Antépara Ercoreca A Arnedillo Muñoz F Barbe Illa B Barreiro López M Blanco Aparicio A Boada Valmaseda M Bosque García A Bustamante Ruiz P Carretero Anibarro F Del Campo Matias Jm Echave-sustaet Espinosa De Los Monteros Garde Mj Garcia Hernandez Gm A López Viña L Lores Obradors Luengo Planas Mt E Monsó Molas A Navarro Dourdil Nieto García Aj M Perpina Tordera C Picado Valles M Rodriguez Alvarez Mdel A Saura Vinuesa J Serra Batlles Soler Sempere Mj P Toran Montserrat Valdés Cuadrado Lg C Villasante Fernandez-montes Sl Cheng Jh Chern Mh Chiu Cl Chung Rs Lai Ck Lin Yc Liu Cc Wang Yf Wei L Amer Vi Berenfus L Besh Kd Duka Im Fushtey N Garmash O Dudnyk O Godlevska Ma Vlasenko I Hospodarskyy L Iashyna M Kaladze Si Khvelos Vp Kostromina O Krakhmalova T Kryuchko Ov Kulynych Mp Krasko O Levchenko T Litvinova Ss Panina Lm Pasiyeshvili Ln Prystupa Li Romaniuk I Sirenko Vi Synenko Lb Vynnychenko Ri Yatsyshyn I Zaitsev V Zhebel O Zubarenko Cp Arthur V Brown H Burhan R Chaudhuri D Collier Nc Barnes Ej Davies A Ellery S Kwok W Lenney M Nordstrom Hc Pandya Iw Parker K Rajakulasingam P Seddon R Sharma Ec Thomas Ja Wakeling M Abalos-galito C Abboy E Abreu If Ackerman Ia Acosta Aa Adaoag M Ahmed Mi Ali Dr Allen Allen Gg Jr Jj Diogo Dc Allison Lk Alwine Sj Apaliski Rs Arastu Cm Arora D Auerbach Sj Azzam Badar Fl 3rd Jw Baker Jp Barasch Ma Barber R Bardinas-rodriguez Tj Barreiro Rr Baumbach Ce Baur Bs Baxter Jl Beach Rl Beasley Je Beavins Wj Beliveau Mj Benbow Nl Bennett Rl Bennett H Bernal Di Bernstein Ms Blaiss Kw Blumenthal Sr Boas Jl Borders Ja Boscia Wn Boulware Bt Bowling Ba Brabec Dg Bramlet Dp Figueroa Df Brautigam Jm Brownell Tr Bruce Rs Call Ca Campbell Ya Canaan Df Cannon Jm Carpio Ws Cathcart Jp Cevallos Av Chauhan Rb Chuang D Chevalier J Christensen Ta Christensen Mo Christina Rr Chrzanowski Fa Civitarese Jp Clark Dp Clifford Rj Lapidus Ja Coggi Jj Lenz Kr Cohen Bg Collins H Collins A Comellas J Condit Cordasco Em Jr Cn Corder Ra Covar Kd Coverston Sa Croce H Cruz Ct Curtis Pk Daftary D Dalan Sp Dalawari Wc Daly Kc Davis Kw Dawes Ba Decotiis Rf Deluca Dm Desantis De Valle Ol Jl Diaz Jd Diaz Jp Dice A Elizalde Mr Hosler C Dixon La Dobkin Rs Dobrusin Mt Dransfield Wl Ebbeling Jd Edwards Jm Elacion D Elkayam Wt Ellison Jr Elsen Lr Engel Dj Ensz Cl Ericksen Je Ervin C Fang F Abrahamian Vb Farrah Jd Field Hj Fishman R Florea S Nayyar A Focil F Focauld Franco Ma Jr Br Frandsen K Ganti Fl Garcia Wm Lee Ag Garscadden Ea Gatti Am Gellady Ar George Gw Gibbon Gp Gleason P Goldberg Mf Goldstein Ge Gonzalez Rg Gower Ja Grande D Gregory Sd Grubb Rp Guthrie Ta Haas Ks Haft R Hajal Gd Hammond Nn Hansel Vr Hansen Af Harris An Hartman Rr Harvey S Hazan-steinberg Dm Headley Gc Heigerick Bn Heller El Hendrix Jn Herrod Mj Hewitt Rl Hines Ap Hirdt Ja Hirschfield Ks Hoffman Ad Hogan Wc Howland Cc Hsu Fj Hsu Wm Hubbard Jd Hudson C Huffman M Hussain Oc Ioachimescu Ym Ismail Na Jaffrani N Jiang Sw Jones Rs Jordan Ke Joshi Mw Kaashmiri M Kalafer Ba Kamdar Jg Kanuga Nl Kao M Karetzky Jc Katsetos Js Kay Ma Kimmel Sh Kimura Jk Kingsley Sm Mahmood Dc Subich Jl Kirstein Ec Kleerup Rm Klein Dw Koh N Kohli Fa Koura Sp Kovacs J Kratzer Ci Kreit Fm Kreutter Tm Kubicki Jm Labuda Aj Latorre Mm Lara Ae Lechin Jj Lee Md Lee Al Lentnek Kw Lesh Pf Levins Rb Anspach Dm Levinsky Mj Lillestol H Lim Md Livezey Cw Lloyd-turney Rf Lockey Ra Long Mj Lynch Bk Macgillivray Kp Mahadevan Sk Makam Mj Maloney D Mapel Bd Margolis J Margulies Ef Martin Ee Martin M Mascolo H Mataria M Sunbuli Rn Mathur Pn Mattar Km Maynard N Maynard B Mccormick M Mcelya Ce Mcevoy Wc Mckenzie Le Medwedeff Kd Mehta Ir Melamed Jv Meli Bh Merrick Pj Meyers Bt Miller Sm Minton Fg Miranda De Mohar Ch Montenegro Fa Morris Bs Morrison Mh Moss F Munoz Gr Naini Ct Nakamura S Naseeruddin C Nassim Lj Navazo Je Nissim D Norman Ms Oberoi Tm O'connor J Offenberger Rr Orr Ea Osea Wj Paine Nl Rasmussen M Palatnik D Pangtay Ja Panuto M Patel Ms Perera A Perez Peters Ph Jr Pimentel Sm Jr Tm Pluto Mt Pollock Ls Posner Jc Pritchard Kk Pudi Cm Puig Py Qaqundah Mk Radbill St Rahman M Raikhel Hh Raissy Ds Ramstad Es Ranasinghe Os Rangel Se Rapo Sp Raschal Dg Reddy Sm Rehman Sr Reyes Rb Rhodes E Riffer Ps Rihal Riley Ed 4th Dh Rodriguez Cm Rogers Jl Rohlf H Romeu Cw Roney So Ronsick Jb Rosen Ms Rowe Ge Ruoff Eh Ryan Rh Saff N Saini S Anand K Balakrishnan Bs Samuels Rj Samuelson Rj Saniuk Wo Sargeant Mk Saunders W Saway Md Scarupa Mv White Mj Schear Cm Schwarz Rb Scott N Segall Af Seibert V Seidmeyer Mr Seidner Fd Seifer J Serje Ms Shah Sb Shah Pa Shapero Sd Shearer Sq Sheikh Ts Shepherd Er Sher Ld Sher Bh Short Pe Silas Jc Alvey Jc Silverfield Sj Simon S Sitar Dp Skoner Sa Smallow Ba Smart Ca Smith Ke Smith Sk Smith Gc Snyders W Soong J Soufer S Spangenthal Je Stahlman Lg Steele Rk Stegemoller J Stocks Ww Storms J Suen Rz Surowitz Jr Swauger La Taber Ae Tan Se Pratt T Tanus Mm Tarpay Ga Tarshis Jw Tenney Kg Tilghman Me Trevino Be Troyan Sk Twiddy Jd Updegrove Kr Urval Kt Uusinarkaus R Vaela M Van Cleeff S Varano Qd Vo Rj Wainz Ja Wald Sj Wall Rl Wasserman Dl Weinstein Ja Welker B 2nd Wellmon T Wells Hs Wenocur Dl Williams Sl Williams Ph Win Td Wingo Wisman Pp Jr Da Wyszomierski Hm Yamada S Yarows Yunger Tm Jr Rw. Ziering

subject

Male asthma ; serious events ; fluticasone ; salmeterol ; AUSTRI Exacerbation Intention to Treat Analysi INHALED CORTICOSTEROIDS Severity of Illness Index law.invention 0302 clinical medicine Randomized controlled trial law immune system diseases Ús terapèutic Broncodilatadors 030212 general & internal medicine Child Fluticasone RISK ACTING BETA-AGONISTS; INHALED CORTICOSTEROIDS; RISK; EXACERBATIONS; METAANALYSIS; MORTALITY; SAFETY; DEATH; FDA Medicine (all)Hazard ratio DEATH General Medicine Bronchodilator agents Middle Aged Fluticasone-Salmeterol Drug Combination Bronchodilator Agents Intention to Treat Analysis Anesthesia SAFETY Female Salmeterol FDA medicine.drug Human Adult medicine.medical_specialty Adolescent Settore MED/10 - Malattie Dell'Apparato Respiratorio Fluticasone propionate 03 medical and health sciences Double-Blind Method Internal medicine Administration Inhalation medicine Humans METAANALYSIS Asma Bronchodilator Agent Asthma Aged Proportional Hazards Models Fluticasone-Salmeterol Drug Combination business.industry MORTALITY ACTING BETA-AGONISTS Therapeutic use medicine.disease Asthma respiratory tract diseases EXACERBATIONS 030228 respiratory system Fluticasone Propionate Salmeterol Xinafoate Drug Combination Proportional Hazards Model Fluticasone business

description

BACKGROUND The safe and appropriate use of long-acting beta-agonists (LABAs) for the treatment of asthma has been widely debated. In two large clinical trials, investigators found a potential risk of serious asthma-related events associated with LABAs. This study was designed to evaluate the risk of administering the LABA salmeterol in combination with an inhaled glucocorticoid, fluticasone propionate. METHODS In this multicenter, randomized, double-blind trial, adolescent and adult patients (age, ≥12 years) with persistent asthma were assigned to receive either fluticasone with salmeterol or fluticasone alone for 26 weeks. All the patients had a history of a severe asthma exacerbation in the year before randomization but not during the previous month. Patients were excluded from the trial if they had a history of lifethreatening or unstable asthma. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization). Noninferiority of fluticasone–salmeterol to fluticasone alone was defined as an upper boundary of the 95% confidence interval for the risk of the primary safety end point of less than 2.0. The efficacy end point was the first severe asthma exacerbation. RESULTS Of 11,679 patients who were enrolled, 67 had 74 serious asthma-related events, with 36 events in 34 patients in the fluticasone–salmeterol group and 38 events in 33 patients in the fluticasone-only group. The hazard ratio for a serious asthmarelated event in the fluticasone–salmeterol group was 1.03 (95% confidence interval [CI], 0.64 to 1.66), and noninferiority was achieved (P = 0.003). There were no asthma-related deaths; 2 patients in the fluticasone-only group underwent asthmarelated intubation. The risk of a severe asthma exacerbation was 21% lower in the fluticasone–salmeterol group than in the fluticasone-only group (hazard ratio, 0.79; 95% CI, 0.70 to 0.89), with at least one severe asthma exacerbation occurring in 480 of 5834 patients (8%) in the fluticasone–salmeterol group, as compared with 597 of 5845 patients (10%) in the fluticasone-only group (P<0.001). CONCLUSIONS Patients who received salmeterol in a fixed-dose combination with fluticasone did not have a significantly higher risk of serious asthma-related events than did those who received fluticasone alone. Patients receiving fluticasone–salmeterol had fewer severe asthma exacerbations than did those in the fluticasone-only group. AUSTRI ClinicalTrials.gov number, NCT01475721.

year	journal	country	edition	language
2016-05-12

10.1056/nejmoa1511049 http://hdl.handle.net/10459.1/65688