Safety and efficacy of combined long-acting beta-agonists and inhaled corticosteroids vs long-acting beta-agonists monotherapy for stable COPD: a systematic review.
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.
Rodrigo
Gustavo J
GJ
Departamento de Emergencia, Hospital Central de las Fuerzas Armadas, Montevideo, Uruguay. Electronic address: gurodrig@adinet.com.uy.
Castro-Rodriguez
José A
JA
School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
Plaza
Vicente
V
Servei de Pneumologia, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain.
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
D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D003692:Delayed-Action Preparations