|  |  |  |  | Baseline characteristics | All-cause mortality (binary) | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
References | Trial | Treatment | Dose | Study duration (weeks) | n | Mean age (yr.) | Women (%) | Current smokers (%) | FEV1 (mean % predicted) | Subjects | Deaths - ITT | Deaths – OT |
[53] | Aaron 2007 | Tiotropium + Salmeterol | 18 μg od/50 μg bid | 52 | 148 | 67.6 | 42.6 | 24.3 | 41.2 | 148 | 6 | NR |
Tiotropium + SFC | 18 μg od/50/500 μg bid |  | 145 | 67.5 | 42.1 | 32.4 | 42.2 | 145 | 6 | NR | ||
Tiotropium + Placebo | 18 μg od |  | 156 | 68.1 | 46.2 | 26.9 | 42.1 | 156 | 4 | NR | ||
[40] | Anzueto 2009 | SFC | 50/250 μg bid | 52 | 394 | 65.4 | 49.0 | 42.0 | 41.2 | 394 | 4 | NR |
Salmeterol | 50 μg bid |  | 403 | 65.3 | 43.0 | 43.0 | 40.0 | 403 | 6 | NR | ||
[54] | Bateman 2010 | Tiotropium | 5 μg od | 48 | 1952 | 64.8 | 21.9 | 35.7 | 45.2 | 1952 | 52 | NR |
Placebo | - | Â | 1965 | 64.8 | 23.0 | 35.9 | 45.4 | 1965 | 38 | NR | ||
[55] | ISOLDE (Burge 2000) | Fluticasone Propionate | 500 μg bid | 156 | 376 | 63.7 | 25.0 | 36.4 | 50.3 | 372 | 32 | NR |
Placebo | - | Â | 375 | 63.8 | 26.0 | 39.2 | 50.0 | 370 | 36 | NR | ||
[56] | Calverley 2003 | Budesonide + Formoterol | 320/9 μg bid | 52 | 254 | 64.0 | 22.0 | 33.0 | 36.0 | 254 | 5 | NR |
Budesonide | 400 μg bid |  | 257 | 64.0 | 26.0 | 39.0 | 36.0 | 257 | 6 | NR | ||
Formoterol | 9 μg bid |  | 255 | 63.0 | 25.0 | 36.0 | 36.0 | 255 | 13 | NR | ||
Placebo | - | Â | 256 | 65.0 | 25.0 | 30.0 | 36.0 | 256 | 5 | NR | ||
[5] | TORCH* (Calverley 2007) | Fluticasone Propionate | 500 μg bid | 156 | 1534 | 65.0 | 25.0 | 43.0 | 44.1 | 1534 | 246 | NR |
Salmeterol | 50 μg bid |  | 1521 | 65.1 | 24.0 | 43.0 | 43.6 | 1521 | 205 | NR | ||
SFC | 50/500 μg bid |  | 1533 | 65.0 | 25.0 | 43.0 | 44.3 | 1533 | 193 | NR | ||
Placebo | - | Â | 1524 | 65.0 | 24.0 | 43.0 | 44.1 | 1524 | 231 | NR | ||
[57] | Calverley 2007 | Roflumilast | 500 μg od | 52 | 760 | 65.0 | 25.0 | 38.0 | 41.0 | 760 | 12 | NR |
Placebo | Â | Â | 753 | 64.0 | 24.0 | 35.0 | 41.0 | 753 | 20 | NR | ||
[58] | M2-124 (Calverley 2009) | Roflumilast | 500 μg od | 52 | 765 | 64.0 | 29.0 | 48.0 | 37.6 | 765 | 17 | NR |
Placebo | Â | Â | 758 | 63.0 | 29.0 | 48.0 | 37.5 | 758 | 17 | NR | ||
M2-125 (Calverley 2009) | Roflumilast | 500 μg od | 52 | 772 | 64.0 | 21.0 | 35.0 | 34.6 | 772 | 25 | NR | |
 | Placebo |  |  | 796 | 64.0 | 19.0 | 35.0 | 35.3 | 796 | 25 | NR | |
[59] | Calverley 2010 | Beclomethasone + Formoterol | 200/12μg bid | 48 | 232 | 63.0 | 20.7 | 38.8 | 41.9a | 232 | 2 | NR |
Budesonide + Formoterol | 400/12μg bid |  | 238 | 64.1 | 18.5 | 36.1 | 42.3a | 238 | 4 | NR | ||
Formoterol | 12 μg bid |  | 233 | 63.7 | 18.9 | 37.3 | 42.5a | 233 | 0 | NR | ||
[49] | Campbell 2005 | Formoterol bid + Formoterol | 9 μg bid / 4.5 μg as needed | 26 | 225 | 60.0 | 29.0 | 56.0 | 54.4b | 225 | 1 | NR |
Formoterol bid + Terbutaline | 9μg bid / 0.5 mg as needed |  | 215 | 60.0 | 39.0 | 54.0 | 53.0b | 215 | 2 | NR | ||
Placebo + Terbutaline | 0.5 mg as needed |  | 217 | 60.0 | 27.0 | 55.0 | 54.1b | 217 | 0 | NR | ||
[26] | Casaburi 2005 | Tiotropium | 18 μg od | 25 | 55 | 65.9 | 45.5 | 29.1 | 32.6b | 55 | 1 | NR |
Placebo | - | Â | 53 | 67.3 | 41.5 | 18.9 | 36.2b | 53 | 0 | NR | ||
[27] | Chan 2007 | Tiotropium | 18 μg od | 48 | 608 | 66.8 | 41.0 | 32.0 | 39.4b | 608 | 15 | 13 |
 | Placebo | - |  | 305 | 66.9 | 39.0 | 30.0 | 39.3b | 305 | 4 | 2 | |
[60] | Choudhury 2007 | Fluticasone Propionate | 500 μg bid | 52 | 128 | 67.6 | 52.0 | 40.6 | 53.2 | 128 | 3 | NR |
Placebo | - | Â | 132 | 67.3 | 44.0 | 35.6 | 55.0 | 132 | 0 | NR | ||
[28] | INVOLVE (Dahl 2010) | Indacaterol (300) | 300μg od | 52 | 437 | 64.0 | 19.7 | NR | 51.5 | 437 | 1 | 1 |
Indacaterol (600) | 600μg od |  | 425 | 63.0 | 23.1 | NR | 50.8 | 428 | 1 | 0 | ||
Formoterol | 12μg (bid) |  | 434 | 64.0 | 19.8 | NR | 52.5 | 435 | 5 | 3 | ||
Placebo | - | Â | 432 | 63.0 | 18.5 | NR | 52.0 | 432 | 5 | 4 | ||
[29] | Donohue 2002 | Salmeterol | 50 μg bid | 26 | 213 | 64.6 | 25.0 | NR | 40.2bc | 213 | 3 | NR |
Tiotropium | 18 μg od |  | 209 | 64.5 | 26.0 | NR | 40.2bc | 209 | 0 | NR | ||
Placebo | - | Â | 201 | 65.6 | 25.0 | NR | 40.2bc | 201 | 4 | NR | ||
[30] | INHANCE (Donohue 2010) | Indacaterol (150) | 150 μg od | 26 | 416 | 63.4 | 37.7 | NR | 56.1 | 416 | 1 | NR |
Indacaterol (300) | 300 μg od |  | 416 | 63.3 | 36.8 | NR | 56.3 | 416 | 0 | NR | ||
Tiotropium | 18 μg od |  | 415 | 64.0 | 35.2 | NR | 53.9 | 415 | 2 | NR | ||
Placebo | - | Â | 418 | 63.6 | 39.0 | NR | 56.1 | 418 | 0 | NR | ||
[31] | Ferguson 2008 | SFC | 250/50 μg bid | 52 | 394 | 64.9 | 42.0 | 40.0 | 39.8 | 394 | 6 | NR |
Salmeterol | 50 μg bid |  | 388 | 65.0 | 48.0 | 38.0 | 40.6 | 388 | 3 | NR | ||
[32] | Hanania 2003 | Fluticasone Propionate | 250 μg bid | 24 | 183 | 63.0 | 34.0 | 48.0 | 42.0b | 183 | 0 | NR |
Salmeterol | 50 μg bid |  | 177 | 64.0 | 42.0 | 51.0 | 42.0 | 177 | 0 | NR | ||
SFC | 250 / 50 μg bid |  | 178 | 63.0 | 39.0 | 43.0 | 41.0 | 178 | 0 | NR | ||
Placebo | - | Â | 185 | 65.0 | 32.0 | 47.0 | 42.0b | 185 | 0 | NR | ||
[33] | VIVACE (Kardos 2007) | Salmeterol | 50 μg bid | 44 | 487 | 64.0 | 22.4 | 44.4 | 40.3 | 487 | 9 | NR |
SFC | 50/500 μg bid |  | 507 | 63.8 | 26.0 | 40.6 | 40.4 | 507 | 7 | NR | ||
[41] | Kerstjens 1992 | Ipratropium Bromide + Terbutaline | 800/2000 μg bid | 130 | 92 | 38.9 | 36.0 | 34.0 | 63.3a | 92 | 0 | NR |
Beclomethasone + Terbutaline | 160/2000 μg bid |  | 91 | 40.2 | 35.0 | 36.0 | 64.6a | 91 | 0 | NR | ||
Placebo + Terbutaline | na/2000 μg bid |  | 91 | 39.6 | 36.0 | 37.0 | 63.3a | 91 | 0 | NR | ||
[42] | INLIGHT-2 (Kornmann 2011) | Indacaterol | 150 μg od | 26 | 330 | 63.0 | 28.0 | 46.0 | 54.0 | 330 | 1 | NR |
Salmeterol | 50 μg bid |  | 333 | 63.0 | 25.0 | 46.0 | 53.0 | 333 | 0 | NR | ||
Placebo | - | Â | 335 | 64.0 | 23.0 | 45.0 | 53.0 | 335 | 3 | NR | ||
[34] | Mahler 2002 | Fluticasone Propionate | 500 μg bid | 24 | 168 | 64.4 | 39.0 | 46.0 | 41.0b | 168 | 0 | NR |
Salmeterol | 50 μg bid |  | 160 | 63.5 | 36.0 | 46.0 | 40.0b | 160 | 0 | NR | ||
SFC | 50 / 500 μg bid |  | 165 | 61.9 | 38.0 | 46.0 | 41.0b | 165 | 0 | NR | ||
Placebo | - | Â | 181 | 64.0 | 25.0 | 54.0 | 41.0b | 181 | 3 | NR | ||
[61] | Niewoehner 2005 | Tiotropium | - | 26 | 914 | 67.6 | 2.0 | 29.0 | 35.6b | 914 | 22 | NR |
Placebo | 18 μg od |  | 915 | 68.1 | 1.0 | 30.0 | 35.6b | 915 | 19 | NR | ||
[22] | EUROSCOP (Pauwels 1999) | Budesonide | 400μg bid | 156 | 634 | 52.5 | 26.5 | 100.0 | 76.8a | 634 | 8 | NR |
Placebo | - | Â | 643 | 52.4 | 27.8 | 100.0 | 76.9a | 643 | 10 | NR | ||
[35] | Rennard 2009 | Budesonide + Formoterol | 320/9 μg bid | 52 | 494 | 63.2 | 37.7 | 39.1 | 38.6 | 494 | 8 | 3 |
Budesonide + Formoterol | 160/9 μg bid |  | 494 | 63.6 | 37.2 | 41.9 | 39.6 | 494 | 8 | 6 | ||
Formoterol | 9 μg bid |  | 495 | 62.9 | 34.7 | 45.1 | 39.3 | 495 | 6 | 2 | ||
Placebo | - | Â | 481 | 62.9 | 34.7 | 43.9 | 40.8 | 481 | 8 | 4 | ||
[36] | FICOPD II (Rossi 2002) | Formoterol 12 | 12 μg bid | 52 | 211 | 63.0 | 13.0 | NR | 47.0b | 211 | 3 | NR |
Formoterol 24 | 24 μg bid |  | 214 | 62.0 | 17.0 | NR | 47.0b | 214 | 1 | NR | ||
Theophylline | 200/300 mg bid | Â | 209 | 64.0 | 18.0 | NR | 46.0b | 209 | 0 | NR | ||
Placebo | - | Â | 220 | 63.0 | 21.0 | NR | 49.0b | 220 | 0 | NR | ||
[62] | Schermer 2009 | Fluticasone Propionate | 500 μg bid | 156 | 94 | 58.4 | 27.0 | 62.0 | 68.7b | 94 | 8 | NR |
Placebo | - | Â | 96 | 59.6 | 32.0 | 51.0 | 71.4b | 96 | 3 | NR | ||
[23] | Shaker 2009 | Budesonide | 400 μg bid | 208 | 127 | 63.6 | 38.0 | 100.0 | 51.0b | 127 | 5 | NR |
Placebo | - | Â | 127 | 63.6 | 46.0 | 100.0 | 53.0b | 127 | 5 | NR | ||
[43] | Stockley 2006 | Salmeterol | 50 μg bid | 52 | 318 | 62.3 | 24.0 | 46.0 | 45.8b | 216 | 6 | NR |
Placebo | - | Â | 316 | 62.4 | 23.0 | 47.0 | 46.1b | 222 | 5 | NR | ||
[37] | Szafranski 2003 | Budesonide + Formoterol | 320/9 μg bid | 52 | 208 | 64.0 | 24.0 | 30.0 | 36.0b | 208 | 6 | NR |
Budesonide | 400 μg bid |  | 198 | 64.0 | 20.0 | 36.0 | 37.0b | 198 | 5 | NR | ||
Formoterol | 9 μg bid |  | 201 | 63.0 | 24.0 | 38.0 | 36.0b | 201 | 6 | NR | ||
Placebo | - | Â | 205 | 65.0 | 17.0 | 34.0 | 36.0b | 205 | 9 | NR | ||
[63] | Tashkin 2008 | Budesonide + Formoterol | 320/9 μg bid | 26 | 277 | 63.1 | 32.1 | 44.4 | 39.1 | 277 | 3 | NR |
Budesonide + Formoterol | 160/9 μg bid |  | 281 | 63.6 | 35.6 | 44.8 | 39.9 | 281 | 4 | NR | ||
Budesonide + Formoterol | 320 + 9 μg bid (separate) |  | 287 | 63.7 | 25.8 | 41.5 | 39.2 | 287 | 0 | NR | ||
Budesonide | 320 μg bid |  | 275 | 63.4 | 32.4 | 42.9 | 39.7 | 275 | 2 | NR | ||
Formoterol | 9 μg bid |  | 284 | 63.5 | 34.5 | 41.9 | 39.6 | 284 | 1 | NR | ||
Placebo | - | Â | 300 | 63.2 | 31.0 | 39.7 | 41.3 | 300 | 1 | NR | ||
UPLIFT (Tashkin 2008/Celli 2009) | Tiotropium | 18 μg od | 208 | 2986 | 64.5 | 24.6 | 29.3 | 47.7 | 2987 | 446 | 381 | |
Placebo | - | Â | 3006 | 64.5 | 26.1 | 29.9 | 47.4 | 3006 | 495 | 411 | ||
[44] | Tonnel 2008 | Tiotropium | 18 μg od | 39 | 266 | 64.9 | 13.2 | 23.7 | 47.5b | 266 | 3 | NR |
Placebo | Â | Â | 288 | 63.5 | 14.6 | 30.2 | 46.2b | 288 | 6 | NR | ||
[45] | COPE (van der Valk 2002) | Fluticasone Propionate | 500 μg bid | 26 | 123 | 64.1 | 14.6 | 22.0 | 57.5 | 123 | 1 | NR |
Placebo | - | Â | 121 | 64.0 | 16.5 | 33.3 | 56.1 | 121 | 1 | NR | ||
[46] | CCLS (Vestbo 1999) | Budesonide | 800 μg od + 400 μg od for 6 months; 400 μg bid for 30 month | 156 | 145 | 59.0 | 41.4 | 75.9 | 86.2 | 145 | 4 | NR |
Placebo | - | Â | 145 | 59.1 | 37.9 | 77.2 | 86.9 | 145 | 5 | NR | ||
[38] | Vogelmeier 2008 | Formoterol | 10 μg bid | 24 | 210 | 61.8 | 24.3 | NR | 51.6b | 210 | 0 | NR |
Tiotropium | 18 μg od |  | 221 | 63.4 | 20.8 | NR | 51.6b | 221 | 0 | NR | ||
Tiotropium + Formoterol | 18 μg od/10 μg bid |  | 207 | 62.6 | 20.8 | NR | 50.4 | 207 | 0 | NR | ||
Placebo | - | Â | 209 | 62.5 | 22.5 | NR | 51.1 | 209 | 1 | NR | ||
[47] | POET-COPD 2011 (Vogelmeier 2011) | Tiotropium | 18 μg od | 52 | 3707 | 62.9 | 25.6 | 48.0 | 49.2 | 3707 | 64 | 66 |
Salmeterol | 50 μg bid |  | 3669 | 62.8 | 25.1 | 48.3 | 49.4 | 3669 | 78 | 73 | ||
[66] | INSPIRE (Wedzicha 2008) | SFC | 50/500 μg bid | 104 | 658 | 64.0 | 19.0 | 38.0 | 39.1 | 658 | 21 | 18 |
Tiotropium | 18 μg od |  | 665 | 65.0 | 16.0 | 38.0 | 39.4 | 665 | 38 | 34 | ||
[24] | LHS (Wise 2000) | Triamcinolone | 600 μg bid | 156 | 559 | 56.2 | 36.0 | 90.5 | 68.5 | 559 | 15 | NR |
Placebo | - | Â | 557 | 56.4 | 37.9 | 89.8 | 67.2 | 557 | 19 | NR | ||
[39] | Zheng 2007 | SFC | 50/500 μg bid | 24 | 297 | 66.0 | 9.4 | 21.0 | 47.0b | 297 | 2 | NR |
Placebo | - | Â | 148 | 66.6 | 13.5 | 23.0 | 47.0b | 148 | 0 | NR | ||
[48] | Zhong 2012 | Budesonide + Formoterol | 320/9 μg bid | 26 | 156 | 65.7 | 1.9 | NR | 36.2 | 156 | 1 | NR |
Budesonide | 400 μg bid |  | 152 | 64.7 | 7.9 | NR | 36.3 | 152 | 0 | NR |