title: Efficacy and safety of a fixed-dose combination of indacaterol and Glycopyrronium for the treatment of COPD: a systematic review.
abstract: BACKGROUND
  COPD guidelines recommend the combined use of inhaled, long-acting β2-agonists and long-acting muscarinic antagonists if symptoms are not improved by a single agent. This systematic review assessed the efficacy and safety of the fixed-dose combination of the long-acting β2-agonist indacaterol and long-acting muscarinic antagonist glycopyrronium (QVA149) compared with its monocomponents (glycopyrronium and indacaterol) and tiotropium for the treatment of moderate to severe COPD.
  
  
  METHODS
  This was a systematic review of randomized, placebo-controlled or crossover trials (3-64 weeks). Primary outcomes were trough FEV1, severe adverse events, and serious cardiovascular events.
  
  
  RESULTS
  Five trials (4,842 patients) were included. Compared with tiotropium, QVA149 showed a significant increase in trough FEV1 (70 mL; P < .0001) and a decreased use of rescue medication (-0.63 puffs/d; P < .0001). Patients receiving QVA149 had a 19% greater likelihood of experiencing a minimal clinical important difference (MCID) in the number needed to treat for benefit (NNTB) (NNTB = 11) and a 16% greater likelihood of achieving an MCID in the St. George's Respiratory Questionnaire (SGRQ) (NNTB = 11). Similarly, QVA149 vs glycopyrronium showed a significant increase in trough FEV1 (70 mL; P < .0001), a significant reduction in rescue medication use (-0.59; P < .0001), and a significant increase in the rate of patients achieving an MCID in the SGRQ (NNTB = 12). QVA149 showed similar levels of safety and tolerability to both comparators. It was not possible to perform a pooled analysis of data comparing QVA149 vs indacaterol.
  
  
  CONCLUSIONS
  Once-daily, inhaled QVA149 showed superior efficacy compared with glycopyrronium and the current standard of care, tiotropium, in patients with moderate to severe COPD.
authors.affiliation: Departamento de Emergencia (Dr Rodrigo), Hospital Central de las Fuerzas Armadas, Montevideo, Uruguay, Spain; Servei de Pneumologia (Dr Plaza), Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain. Electronic address: gustavo.javier.rodrigo@gmail.com.
authors.forename: Gustavo J
authors.initials: GJ
authors.lastname: Rodrigo
authors.affiliation: Departamento de Emergencia (Dr Rodrigo), Hospital Central de las Fuerzas Armadas, Montevideo, Uruguay, Spain; Servei de Pneumologia (Dr Plaza), Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Plaza
mesh_terms: D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006024:Glycopyrrolate / Q000008:administration & dosage*; D006801:Humans; D007189:Indans / Q000008:administration & dosage*; D018727:Muscarinic Antagonists / Q000008:administration & dosage; D017410:Practice Guidelines as Topic; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D015363:Quinolones / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D007189:Indans; D018727:Muscarinic Antagonists; D015363:Quinolones; C510790:indacaterol; D006024:Glycopyrrolate