title: The effects of long-acting bronchodilators on total mortality in patients with stable chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Chronic obstructive pulmonary disease (COPD) is the 4th leading cause of mortality worldwide. Long-acting bronchodilators are considered first line therapies for patients with COPD but their effects on mortality are not well known. We performed a comprehensive systematic review and meta-analysis to evaluate the effects of long-acting bronchodilators on total mortality in stable COPD.
  
  
  METHODS
  Using MEDLINE, EMBASE and Cochrane Systematic Review databases, we identified high quality randomized controlled trials of tiotropium, formoterol, salmeterol, formoterol/budesonide or salmeterol/fluticasone in COPD that had a follow-up of 6 months or longer and reported on total mortality. Two reviewers independently abstracted data from the original trials and disagreements were resolved by iteration and consensus.
  
  
  RESULTS
  Twenty-seven trials that included 30,495 patients were included in the review. Relative risk (RR) for total mortality was calculated for each of the study and pooled together using a random-effects model. The combination of inhaled corticosteroid (ICS) and long-acting beta-2 agonist (LABA) therapy was associated with reduced total mortality compared with placebo (RR, 0.80; p = 0.005). Neither tiotropium (RR, 1.08; p = 0.61) nor LABA by itself (RR, 0.90; p = 0.21) was associated with mortality.
  
  
  CONCLUSIONS
  A combination of ICS and LABA reduced mortality by approximately 20%. Neither tiotropium nor LABA by itself modifies all-cause mortality in COPD.
authors.affiliation: Department of Medicine (Respiratory Division), University of British Columbia, 6040 Iona Drive, Vancouver, V6T 2E8, Canada.
authors.forename: Agnes
authors.initials: A
authors.lastname: Kliber
authors.forename: Larry D
authors.initials: LD
authors.lastname: Lynd
authors.forename: Don D
authors.initials: DD
authors.lastname: Sin
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use*; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D018680:Cholinergic Antagonists / Q000627:therapeutic use*; D004338:Drug Combinations; D019317:Evidence-Based Medicine; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000401:mortality*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D004338:Drug Combinations
references.citation: Chest. 2003 Oct;124(4):1350-6
references.pmid: 14555565
references.citation: Thorax. 2005 Jun;60(6):480-7
references.pmid: 15923248
references.citation: Am J Respir Crit Care Med. 2007 Jan 15;175(2):144-9
references.pmid: 17053207
references.citation: Drugs. 2008;68(14):1975-2000
references.pmid: 18778120
references.citation: Drugs. 2009;69(5):549-65
references.pmid: 19368417
references.citation: Eur Respir J. 2002 Feb;19(2):217-24
references.pmid: 11866001
references.citation: Lancet. 2003 Feb 8;361(9356):449-56
references.pmid: 12583942
references.citation: PLoS Med. 2006 Nov;3(11):e442
references.pmid: 17132052
references.citation: J Am Geriatr Soc. 2001 May;49(5):571-6
references.pmid: 11380749
references.citation: Lancet. 1997 May 24;349(9064):1498-504
references.pmid: 9167458
references.citation: Can Respir J. 2007 Sep;14 Suppl B:5B-32B
references.pmid: 17885691
references.citation: Am J Respir Crit Care Med. 2005 Sep 15;172(6):704-12
references.pmid: 15860753
references.citation: Thorax. 2006 Oct;61(10):854-62
references.pmid: 16844726
references.citation: Eur Respir J. 2008 Dec;32(6):1451-7
references.pmid: 18799503
references.citation: Am J Respir Crit Care Med. 2006 Apr 1;173(7):736-43
references.pmid: 16424444
references.citation: N Engl J Med. 2008 Oct 9;359(15):1543-54
references.pmid: 18836213
references.citation: Cochrane Database Syst Rev. 2007 Oct 17;(4):CD006826
references.pmid: 17943917
references.citation: Respir Med. 2008 Aug;102(8):1099-108
references.pmid: 18614347
references.citation: Am J Respir Crit Care Med. 2009 Nov 15;180(10):948-55
references.pmid: 19729663
references.citation: Ann Intern Med. 2005 Sep 6;143(5):317-26
references.pmid: 16144890
references.citation: Am J Respir Crit Care Med. 2008 Jun 1;177(11):1207-14
references.pmid: 18310480
references.citation: Am J Respir Crit Care Med. 2008 Jan 1;177(1):19-26
references.pmid: 17916806
references.citation: Am J Respir Crit Care Med. 2002 Oct 15;166(8):1084-91
references.pmid: 12379552
references.citation: Eur Respir J. 2002 Feb;19(2):209-16
references.pmid: 11871363
references.citation: Control Clin Trials. 1996 Feb;17(1):1-12
references.pmid: 8721797
references.citation: Thorax. 2007 Jul;62(7):595-601
references.pmid: 17356059
references.citation: Ann Intern Med. 2009 Oct 20;151(8):517-27
references.pmid: 19841453
references.citation: Thorax. 2003 May;58(5):399-404
references.pmid: 12728159
references.citation: Chest. 2009 Oct;136(4):1029-1038
references.pmid: 19633090
references.citation: Thorax. 2007 Nov;62(11):938-43
references.pmid: 17557771
references.citation: Lancet. 2008 Oct 25;372(9648):1473-83
references.pmid: 18835640
references.citation: Am J Respir Crit Care Med. 2007 Sep 15;176(6):532-55
references.pmid: 17507545
references.citation: JAMA. 2008 Nov 26;300(20):2407-16
references.pmid: 19033591
references.citation: N Engl J Med. 1974 Oct 10;291(15):755-8
references.pmid: 4414996
references.citation: Thorax. 2006 Feb;61(2):115-21
references.pmid: 16055612
references.citation: Thorax. 2006 Feb;61(2):122-8
references.pmid: 16443706
references.citation: N Engl J Med. 2007 Feb 22;356(8):775-89
references.pmid: 17314337
references.citation: Respir Med. 2008 Nov;102(11):1511-20
references.pmid: 18804362
references.citation: N Engl J Med. 2004 Jun 24;350(26):2645-53
references.pmid: 15215480
references.citation: Eur Respir J. 2003 Dec;22(6):912-9
references.pmid: 14680078
references.citation: Int J Chron Obstruct Pulmon Dis. 2008;3(2):301-10
references.pmid: 18686739
references.citation: Eur Respir J. 2003 Jan;21(1):74-81
references.pmid: 12570112
references.citation: Lancet. 1997 May 17;349(9063):1436-42
references.pmid: 9164317
references.citation: Control Clin Trials. 1997 Dec;18(6):530-45; discussion 546-9
references.pmid: 9408716
references.citation: Eur Respir J. 2009 Nov;34(5):1018-23
references.pmid: 19880616
references.citation: Can Respir J. 2007 Nov-Dec;14(8):465-72
references.pmid: 18060091
references.citation: Ann Intern Med. 2008 Sep 16;149(6):380-90
references.pmid: 18794557
references.citation: Chest. 2007 Dec;132(6):1756-63
references.pmid: 17951625
references.citation: Arch Intern Med. 2009 Aug 10;169(15):1403-10
references.pmid: 19667304
references.citation: COPD. 2009 Oct;6(5):320-9
references.pmid: 19863361
references.citation: JAMA. 2008 Sep 24;300(12):1439-50
references.pmid: 18812535
references.citation: Am J Respir Med. 2003;2(1):67-74
references.pmid: 14720023
references.citation: Cochrane Database Syst Rev. 2007 Oct 17;(4):CD003794
references.pmid: 17943798
references.citation: Ann Intern Med. 2007 Apr 17;146(8):545-55
references.pmid: 17310045