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N Engl J Med. 2011 Mar 24;364(12):1093-1103. doi: 10.1056/NEJMoa1008378.

Tiotropium versus salmeterol for the prevention of exacerbations of COPD.

Collaborators (759)

Sommersgutter M, Block LH, Pohl W, Sweilem M, Zehetner E, Köberl GH, Kühteubl G, Wild M, Moder G, Popovic R, Wallner G, Voves R, Wanke T, Holub G, Würtz J, Würtz P, Studnicka M, Kaik G, Capiau L, Martinot JB, Bombled P, Bous JP, De Meulemeester M, Feys P, Henry G, Teheux J, Van Stee J, Balthazar Y, Descamps F, Dimitrova R, Youroukova V, Dimova D, Ivanov S, Dimitrov V, Stefanova B, Noleva K, Radkov Y, Terziev C, Hodzhev V, Machkovska M, Metev H, Ali M, Burdova E, Buresova M, Bursova J, Dindos J, Frátrik J, Hartman P, Havlik M, Havlikova A, Havlova E, Hojka I, Jensovsky V, Jirmanova I, Kalandrova K, Kalina P, Klenerova E, Kolman P, Krenarova J, Mares J, Matulova A, Pekarek Z, Povysilova L, Presperinova J, Vondra V, Zajicova O, Zakova L, Zoula J, Veverka J, Kolarikova R, Evald T, Høegholm A, Meyer CN, Enk B, Sørensen T, Madsen F, Døssing M, Jakobsen KS, Wessels J, Hansen M, Hakulinen A, Kotaniemi J, Elo J, Pietiläinen M, Venho K, Torkko M, Niemelä I, Backman R, Järvinen P, Kauppinen R, Blanc FX, Pinet C, Lebas FX, Dupouy J, Krai D, Kessler R, Milhe F, Mounier D, Faraut C, Bellon-Serre B, Taieb S, Ducolone A, Smolis A, Bouchaert E, Bettendorf A, Verdier S, Dussart L, de Lafond TG, Kafe H, Devouassoux G, Maurisset O, Maurer C, Perche A, Perelroizen H, Boyer GR, Rochefort-Morel C, Monchatre M, Marangoni E, Castelli B, Rabaud D, Ravier C, Bourgeois O, Boyes JP, Devenyns F, Garrigue L, Kressmann E, Lafaurie B, Amblard P, Charrier B, Churet JB, Flosi M, Gabrielli JL, Navarre V, Rousset A, Amate M, Bourdrel L, Simon V, Jasnot JY, Kampschulte J, Schaupp R, Hector H, Ritter L, Thomas C, Dersidan A, Bründermann HW, Hauk J, Horstmeier U, Schulte-Braucks R, Jacubasch T, Möwius A, Zimny H, Gebhardt W, Weyland K, Deutscher HW, Klemm G, Kellner BT, Schneebauer T, Piroth J, Pohl V, Pustelnik A, Bindig HW, Grosskopf W, Dentler R, Hossbach E, Koch T, Lehmann G, Peters O, Riegel P, Theis GK, Weber D, Abdul-Malak P, Barth D, Becker C, Eyck M, Erdle W, Kessel J, Lohmann A, Henning V, Stenzel H, Stuff K, Wasner P, Schmidtmann S, Benedix A, Micke L, Hofmann S, Engelhard R, Udosic J, Luttermann M, Merke J, Molitor S, Jander R, Ziegner A, Petig G, Besser O, Böhm R, Dorsch W, Triebel A, Asten S, Babyesiza A, Baumann E, Beck E, Lehnert J, Radermacher E, Götze M, Heinz GU, Vorderstrasse W, Bieler T, Lässig T, Overlack A, Dünzel M, Gröschel W, Riffelmann F, Eisel E, Deckelmann R, Kroemer B, Auge D, Saur J, Hoheisel G, Hennig R, Huber RM, Wiemer S, Junggeburth J, Petermann W, Pettenkofer J, Prehn U, Bezler A, Brüggen H, Grimm-Sachs V, Eilers A, Linnhoff A, Mitlehner W, Thomas J, Trümper BG, Vogelmeier C, von Versen LH, Weber H, Schönen J, Schürmann W, Pumpe K, Seiz V, Tross H, Becker J, Luther R, Schroers M, Rabe U, Rau W, Remppis R, Heschel U, Hellmann A, Kässner F, Koch A, Gessner C, Jasch B, Kühne P, Mueller H, Peslis N, Selbitschka M, Steffen H, Sudhoff H, Ohmer M, Gebhardt T, Winkler J, Behler G, Polke K, Botzen U, Unland M, Raack BW, Aries S, Hissnauer KG, Trauth HA, Husmann R, Korduan M, Petri M, Lenk U, Savaser C, Preiss G, Welss C, Martin H, Angerer M, Berg P, Bettig U, Böhm K, Fleck H, Groth J, Liefring E, Winkels W, Müller J, Sebert M, Havasi-Jost G, Westphal A, Kleinecke-Pohl U, Korth-Wiemann B, Schmorell B, Lindemann L, Trainer C, Gehling U, Eichler M, Lienert T, Schaefer A, Eller J, Arievich H, Babinszky E, Balikó Z, Bartha A, Bauknecht É, Csollák M, Csontos Z, Györi Z, Huszár T, Jedlinszki M, Kelen G, Kónya Melinda M, Kiss B, Lantos J, Major K, Mészáros I, Mitrovics K, Nagy E, Naményi M, Pánczél G, Radeczky E, Rakvács M, Schlezák J, Szalai Z, Szentesi M, Sztancsik Z, Tolnay E, Varga A, Vinkler I, Somfay A, Ariel A, Kramer MR, Ben-Dov I, Breuer R, Fink G, Lieberman D, Yigla M, Raz M, Vilayi-Weiler Z, Weiler-Ravell D, Beckerman M, Cahan C, Goldstein N, Stav D, Ronco M, Fracchia C, Giuseppe LM, Giovanni PL, Potena A, Pirina P, Gian FT, Brusasco V, Pisati G, Cremona GI, Di Maria G, Fabbri L, Micallef E, Paggiaro PL, Pistelli R, Pozzi E, Sanduzzi Zamparelli A, Santelli G, Babjoniseva A, Borsa L, Bukovskis M, Harasimjukas D, Iesalniece R, Petersone A, Smiltena I, Krams A, Lapkovska Z, Eglite R, Santa A, Petrova I, Puzule S, Kiziela A, Naudziunas A, Gumbrevicius G, Visokinskas A, Zebiene E, Valius L, Mikutiene R, Naudziunas S, Leisyte P, Griskeviciene V, Matukiene V, Venceviciene L, Juskiene Z, Vaicius D, van Kempen WW, Agous I, Tan T, de Schipper L, Elle S, Hoivik HO, Tandberg A, Henrichsen S, Kjelsberg F, Gronert JO, Weisser LK, Rødølen T, Helberg S, Zafran GN, Kjaernli T, Pal N, Antczak A, Asankowicz-Bargiel B, Batura-Gabryel H, Bozek A, Bukowczan Z, Chazan R, Chyczewska E, Cieslak M, Cieslicki J, Sikora B, Gawlik R, Gorecka D, Gross-Tyrkin E, Grzelewska-Rzymowska I, Herbowska J, Hofman T, Jankowska R, Jasieniak-Pinis G, Jassem E, Kaczmarek B, Kania G, Karpinski J, Kliks K, Mierzejewska MJ, Korzeniak R, Kot A, Kowalczyk HK, Kus J, Laczynska-Kozerska E, Liebhart J, Madra-Rogacka D, Majorek-Olechowska B, Malosek D, Milanowski J, Mincewicz G, Mroz RM, Nowak D, Obtulowicz K, Pajor A, Pierzchala W, Piotrowicz P, Piotrowski W, Pisarczyk-Bogacka E, Pulka G, Rajtar I, Roslan A, Rozycka-Grudniewicz M, Rybacki C, Sankowski Z, Sciborski R, Sidorowicz-Bialynicka A, Siergiejko Z, Skucha W, Slominski JM, Labij V, Springer E, Stepka M, Szafranski W, Szelerska-Twardosz H, Szmidt M, Szotrowski J, Tarnowska-Matusiak M, Kachel T, Mierzwa W, Trawinska E, Trebas-Pietras E, Witkiewicz I, Wojnowski P, Wytrychowski K, Zalc-Budziszewska E, Ziolo G, Ziora D, Niezgoda K, Szumlanska Z, Smalera E, Napora P, Leszczynski W, Pasternak D, Zurowska-Gebala M, Przysiecki T, Dobryniewska M, Kabata W, Rosinska-Migda J, Lupinska H, Bortkiewicz J, Brzecki K, Andrzejewski W, Doboszynska A, Porawska W, Regula J, Maciejewska K, Krupa-Borek I, Lubinski W, Domingos A, Brito U, Goes L, Pereira J, Coelho L, Antunes A, Alves C, Lino A, Gasparinho C, Reis J, Freitas G, Tatar VA, Stoicescu PI, Savu A, Marta M, Voiculescu M, Gainaru D, Mihalache LV, Stroescu S, Fierbinteanu-Braticevici CG, Bruckner I, Ungureanu G, Ioncica L, Voinea F, Jimborean G, Tint D, Arghir OC, Tudoran M, Nistor S, Cioban TD, Boisteanu D, Tanasescu C, Lenskaya L, Ogorodova L, Ivleva A, Fassakhov R, Volkova E, Libov I, Shostak N, Chuchalin AG, Reshetko O, Barbarash O, Logvinenko N, Martynenko T, Shpagina L, Smolenskaya O, Sherenkov A, Khokhlov A, Ilkovich M, Nemtsov B, Simanenkov V, Trofimov V, Mazurov V, Gorenkov R, Bugrova O, Martynov A, Stryuk R, Yarokhno N, Shmelev EI, Martynenko V, Cherkashina I, Bukreeva E, Tebloev K, Ballyzek M, Dvornikov V, Gorelov A, Leshchenko I, Tereschenko S, Bokarev I, Belenkiy D, Alexeeva L, Idrisova E, Pavlysh E, Berkovich O, Boyarkin M, Arkhipov M, Storozhakov G, Zadionchenko V, Treshkur T, Krivosheev A, Shilkina N, Tokmalaev A, Bezlepko A, Tkachev A, Gamal E, Vasilyeva N, Vyortkin A, Arutyunov G, Popova V, Izmozherova N, Podzolkov V, Sidorenko I, Shestakova G, Pavlishchuk S, Antonovsky Y, Arkhipovsky V, Osipenko M, Esina A, Shutyak T, Yablonsky P, Ragozina N, Polkanova E, Esip V, Kuzin A, Ignatova G, Komar S, Koziolova N, Galvas N, Berezina N, Butko D, Pistraya T, Zagorodsky A, Zilber E, Polevtsova G, Soloviev K, Andreevsky S, Raspopina N, Yakushin S, Agafina A, Khurukhurova N, Stitsenko IA, Agapov V, Surovov A, Horvathova H, Hrebenar S, Jurco P, Kubikova Y, Michalickova M, Mihalecova Y, Pribulova E, Ruziakova V, Flezar M, Ulcar-Kostic S, Cafuta AM, Letonja S, Smonkar T, Vulkelic K, Roca J, Gea J, Monso E, de Lucas P, Barbe F, Alvarez-Sala JL, Barreiro B, Cabrera PL, Cordero P, Sanchez F, Merino J, Agüero R, Corral J, del Campo F, Soler JJ, Signes-Costa J, Salgueiro M, Martinez E, Kongsun-Shum C, Blanquer R, Vennera Mdel C, Luengo Planas M, Berlinches P, Baloira Villar A, Cirak AK, Sahin A, Acican T, Ozkan M, Kiyan E, Yildiz F, Ege E, Gorguner AM, Koksal N, Kocabas A, Gunen H, Basoglu O, Dzyublyk O, Gavrysiuk V, Kostromina V, Palamar B, Grishyna O, Korzh OM, Amer LG, Pertseva T, Rodionova V, Kuriata O, Vdovychenko V, Telyatnikova ZE, Monogarova N, Vizir V, Chernyak V, Koshukova G, Gospodarskyy I, Popik G, Rudyk Y, Biloglazov V, Blazhko V, Panina S, Ignatenko G, Girina O, Kashtelyan O, Voloshyna O, Svintsitskyy A, Mostovoiy Y, Abrahamovych OO, Skrypnyk I, Pasiyeshvily LM, Ostrovskiy M, Netiazhenko V, Dudar L, Romaniuk L, Sakharchuk I, Semidotska Z, Bazylevych A, Vlasenko M, Smolyanyy O, Khodosh E, Putintsev V, Syvolap VV, Fushtey IM, Plesh IA, Diachenko A, Tsokalo V, Feshchenko Y, Iashyna L, Chopyak V, Yabluchanskyy M, Sergiy N, Orpen IM, McCinnon C, George A, Ashe P, Bodalia B, Burge P, Caldwell I, Duffy NC, Ellery A, Higgins BG, Gravil J, Jones N, Jones P, Keaney N, McCaughey M, Mohr SO, Sharma R, Russell R, Simpson H, Smithers A, Takhar AP, Maxwell TG, Adler M, Cahill T, Turner W, Blagden MD, Corris P, Van de Werf F, Senn S, Rudolf M, Krug N, Meyer FJ, John M, Vogelmeier C, Beeh KM, Rutten-van Mölken M.

Author information

  • 1Hospital of the Universities of Giessen and Marburg, Marburg, Germany.

Abstract

BACKGROUND:

Treatment guidelines recommend the use of inhaled long-acting bronchodilators to alleviate symptoms and reduce the risk of exacerbations in patients with moderate-to-very-severe chronic obstructive pulmonary disease (COPD) but do not specify whether a long-acting anticholinergic drug or a β(2)-agonist is the preferred agent. We investigated whether the anticholinergic drug tiotropium is superior to the β(2)-agonist salmeterol in preventing exacerbations of COPD.

METHODS:

In a 1-year, randomized, double-blind, double-dummy, parallel-group trial, we compared the effect of treatment with 18 μg of tiotropium once daily with that of 50 μg of salmeterol twice daily on the incidence of moderate or severe exacerbations in patients with moderate-to-very-severe COPD and a history of exacerbations in the preceding year.

RESULTS:

A total of 7376 patients were randomly assigned to and treated with tiotropium (3707 patients) or salmeterol (3669 patients). Tiotropium, as compared with salmeterol, increased the time to the first exacerbation (187 days vs. 145 days), with a 17% reduction in risk (hazard ratio, 0.83; 95% confidence interval [CI], 0.77 to 0.90; P<0.001). Tiotropium also increased the time to the first severe exacerbation (hazard ratio, 0.72; 95% CI, 0.61 to 0.85; P<0.001), reduced the annual number of moderate or severe exacerbations (0.64 vs. 0.72; rate ratio, 0.89; 95% CI, 0.83 to 0.96; P=0.002), and reduced the annual number of severe exacerbations (0.09 vs. 0.13; rate ratio, 0.73; 95% CI, 0.66 to 0.82; P<0.001). Overall, the incidence of serious adverse events and of adverse events leading to the discontinuation of treatment was similar in the two study groups. There were 64 deaths (1.7%) in the tiotropium group and 78 (2.1%) in the salmeterol group.

CONCLUSIONS:

These results show that, in patients with moderate-to-very-severe COPD, tiotropium is more effective than salmeterol in preventing exacerbations. (Funded by Boehringer Ingelheim and Pfizer; ClinicalTrials.gov number, NCT00563381.).

Comment in

PMID:
21428765
[PubMed - indexed for MEDLINE]
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