title: Safety and efficacy of combined long-acting beta-agonists and inhaled corticosteroids vs long-acting beta-agonists monotherapy for stable COPD: a systematic review.
abstract: BACKGROUND
  Current guidelines recommend the use of inhaled corticosteroids (ICSs) added to long-acting beta(2)-agonists (LABAs) for treatment of symptomatic patients with severe and very severe COPD. However, the evidence has been inconclusive. The aim of this review was to assess the safety and efficacy of LABAs/ICSs compared with LABA monotherapy for patients with moderate-to-very severe COPD.
  
  
  METHODS
  Systematic searches were conducted on MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and the trial registers of manufacturers, without language restriction. Primary outcomes were COPD exacerbations and mortality. Secondary outcomes included lung function, health-related quality of life, and adverse effects.
  
  
  RESULTS
  Eighteen randomized controlled trials (12,446 participants) were selected. Therapy with LABAs/ICSs did not decrease the number of severe exacerbations (relative risk [RR], 0.91; 95% CI, 0.82 to 1.01; I(2) = 1%), or all-cause mortality (RR, 0.90; 95% CI, 0.76 to 1.06; I(2) = 0%), respiratory mortality (RR, 0.80; 95% CI, 0.61 to 1.05; I(2) = 0%), and cardiovascular mortality (RR, 1.22; 95% CI, 0.88 to 1.71; I(2) = 0%). To the contrary, the number of moderate exacerbations (RR, 0.84; 95% CI, 0.74 to 0.96; I(2) = 50%) and the St. George respiratory questionnaire total score (weighted mean difference, -1.88; 95% CI, -2.44 to -1.33; I(2) = 29%) were significantly reduced with LABA/ICS therapy. Although therapy with LABAs/ICSs increases FEV(1) significantly (0.06 and 0.04 L, respectively), they were associated with an increased risk of pneumonia (RR, 1.63; 95% CI, 1.35 to 1.98; I(2) = 20%).
  
  
  CONCLUSIONS
  Compared with LABA monotherapy, the magnitude of the benefits of LABA/ICS therapy did not reach that of the criteria for predefined clinically important effects and were associated with serious adverse effects.
authors.affiliation: Departamento de Emergencia, Hospital Central de las Fuerzas Armadas, Montevideo, Uruguay. Electronic address: gurodrig@adinet.com.uy.
authors.forename: Gustavo J
authors.initials: GJ
authors.lastname: Rodrigo
authors.affiliation: School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: José A
authors.initials: JA
authors.lastname: Castro-Rodriguez
authors.affiliation: Servei de Pneumologia, 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: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D003692:Delayed-Action Preparations