title: Clinical benefit of fixed-dose dual bronchodilation with glycopyrronium and indacaterol once daily in patients with chronic obstructive pulmonary disease: a systematic review.
abstract: OBJECTIVE
  Long-acting bronchodilators are the preferred option for maintenance therapy of patients with chronic obstructive pulmonary disease (COPD). The aim of this review is to provide an overview of the clinical studies evaluating the clinical efficacy of the once-daily fixed-dose dual bronchodilator combination of indacaterol and glycopyrronium bromide in patients suffering from COPD.
  
  
  METHODS
  This study comprised a systematic review of randomized controlled trials identified through systematic searches of different databases of published trials.
  
  
  RESULTS
  Nine trials (6,166 participants) were included. Fixed-dose once-daily indacaterol/glycopyrronium seems to be safe and well tolerated in patients with COPD. Compared with single therapy with other long-acting bronchodilators (indacaterol, glycopyrronium, and tiotropium) and fixed-combination long-acting β2-agonist/inhaled corticosteroid (salmeterol/fluticasone twice daily), once-daily fixed-dose indacaterol/glycopyrronium has clinically important effects on symptoms, including dyspnea score, health status, level of lung function, and rate of moderate or severe exacerbations in patients with moderate-to-very severe COPD (Global initiative for chronic Obstructive Lung Disease [GOLD] spirometric criteria). Furthermore, a very recent study has shown that fixed-dose indacaterol/glycopyrronium improves exercise endurance time compared with placebo, although no significant difference was observed between fixed-dose indacaterol/glycopyrronium and tiotropium.
  
  
  CONCLUSIONS
  Fixed-dose indacaterol/glycopyrronium has clinically relevant effects on important COPD outcome measures and is, in general, superior to therapy with a single long-acting bronchodilator (with or without inhaled corticosteroid) indicating long-acting dual bronchodilation as a potential important maintenance therapeutic option for patients with symptomatic COPD, possibly also for the treatment of naïve patients.
authors.affiliation: Department of Respiratory Medicine, Hvidovre Hospital and University of Copenhagen, Hvidovre, Denmark.
authors.forename: Charlotte Suppli
authors.initials: CS
authors.lastname: Ulrik
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D004338:Drug Combinations; D006024:Glycopyrrolate / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007189:Indans / Q000008:administration & dosage* / Q000009:adverse effects; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D018727:Muscarinic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D015363:Quinolones / Q000008:administration & dosage* / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D020127:Recovery of Function; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D004338:Drug Combinations; D007189:Indans; D018727:Muscarinic Antagonists; D015363:Quinolones; C510790:indacaterol; D006024:Glycopyrrolate
keywords: COPD; glycopyrronium; indacaterol; long-acting bronchodilators
references.citation: COPD. 2005 Mar;2(1):111-24
references.pmid: 17136971
references.citation: COPD. 2005 Mar;2(1):99-103
references.pmid: 17136969
references.citation: Am J Respir Crit Care Med. 2005 Mar 1;171(5):446-52
references.pmid: 15579723
references.citation: Respir Med. 2010 Sep;104(9):1288-96
references.pmid: 20580216
references.citation: Eur Respir J. 2004 Jun;23(6):932-46
references.pmid: 15219010
references.citation: Thorax. 2005 Nov;60(11):925-31
references.pmid: 16055622
references.citation: Chest. 2001 Jan;119(1):85-92
references.pmid: 11157588
references.citation: J Clin Epidemiol. 2009 Oct;62(10):e1-34
references.pmid: 19631507
references.citation: Am J Respir Crit Care Med. 1998 May;157(5 Pt 1):1418-22
references.pmid: 9603117
references.citation: BMJ. 2009 Jul 21;339:b2535
references.pmid: 19622551
references.citation: Thorax. 2010 Dec;65(12):1086-91
references.pmid: 20978028
references.citation: Int J Chron Obstruct Pulmon Dis. 2013;8:501-8
references.pmid: 24159259
references.citation: Eur Respir J. 2013 Dec;42(6):1484-94
references.pmid: 23722616
references.citation: Lancet Respir Med. 2013 Mar;1(1):51-60
references.pmid: 24321804
references.citation: Respir Med. 2013 Oct;107(10):1558-67
references.pmid: 23867808
references.citation: Chest. 2014 May;145(5):981-991
references.pmid: 24385182
references.citation: Chest. 2001 Jul;120(1):258-70
references.pmid: 11451847
references.citation: Chest. 2006 Mar;129(3):536-44
references.pmid: 16537849
references.citation: Am J Respir Crit Care Med. 2001 Aug 1;164(3):358-64
references.pmid: 11500333
references.citation: Am J Respir Cell Mol Biol. 2014 Feb;50(2):337-46
references.pmid: 24032416
references.citation: Am J Respir Crit Care Med. 2013 Feb 15;187(4):347-65
references.pmid: 22878278
references.citation: Respir Med. 2010 Jul;104(7):995-1004
references.pmid: 20303247
references.citation: COPD. 2009 Feb;6(1):17-25
references.pmid: 19229704
references.citation: Respir Med. 2008 Nov;102(11):1511-20
references.pmid: 18804362
references.citation: Thorax. 2002 Oct;57(10):847-52
references.pmid: 12324669
references.citation: Pulm Pharmacol Ther. 2010 Aug;23(4):257-67
references.pmid: 20381630
references.citation: Respir Med. 2014 Apr;108(4):584-92
references.pmid: 24534204
references.citation: Eur Respir J. 2012 Dec;40(6):1545-54
references.pmid: 22835613
references.citation: Lancet Respir Med. 2013 May;1(3):199-209
references.pmid: 24429126
references.citation: Eur Respir J. 2014 Jun;43(6):1599-609
references.pmid: 24176997
references.citation: Eur Respir J. 2005 Aug;26(2):214-22
references.pmid: 16055868
references.citation: COPD. 2010 Dec;7(6):418-27
references.pmid: 21166630
references.citation: Chest. 1994 May;105(5):1411-9
references.pmid: 8181328
references.citation: Thorax. 2012 Sep;67(9):781-8
references.pmid: 22544891