title: The safety of formoterol among patients with asthma using inhaled corticosteroids. Systematic review and meta-analysis.
abstract: BACKGROUND
  It has been postulated that inhaled long acting beta-agonists (LABAs) when used as monotherapy in asthma may increase the incidence of asthma related deaths, intubations and hospitalizations, but concomitant use of inhaled corticosteroids (ICS) may modify this effect.
  
  
  OBJECTIVE
  To assess the safety of formoterol in patients with asthma using ICS.
  
  
  METHODS
  We conducted a systematic review and meta-analysis of parallel group, blinded, randomized controlled trials with at least 12 weeks of treatment examining the impact of twice a day formoterol on asthma-related and total morbidity and mortality in patients concurrently using ICS. Our main analysis considering impact of LABAs (salmeterol and formoterol) has already been published. In this report we present detailed information from studies investigating use of twice daily formoterol among patients receiving ICS.
  
  
  RESULTS
  The search yielded 16 relevant studies included in this analysis. Among over 10,000 participants (5,996 taking formoterol with over 4,000 patient-years observation in formoterol groups) there were 2 asthma-related deaths (both in formoterol groups) and no asthma-related non-fatal intubations. The risk of asthma-related hospitalizations (odds ratio [OR] 0.59, 95% CI 0.37-0.93) and asthma-related serious adverse events (mostly hospitalizations) [OR 0.58, 95% CI 0.37-0.91] were significantly lower in patients on formoterol and ICS compared to patients on ICS alone. The OR for total mortality was 1.22, 95% CI 0.38-3.90, reflecting 7 deaths in formoterol groups and 3 deaths in control groups respectively.
  
  
  CONCLUSIONS
  In patients with asthma using inhaled corticosteroids formoterol decreased the risk of asthma-related hospitalizations. There were too few asthma-related deaths and intubations to establish formoterol's relative impact on these outcomes.
authors.affiliation: Department of Medicine, McMaster University, Hamilton, ON, Canada. jaeschke@mcmaster.ca
authors.forename: Roman
authors.initials: R
authors.lastname: Jaeschke
authors.forename: Paul M
authors.initials: PM
authors.lastname: O'Byrne
authors.forename: Parameswaran
authors.initials: P
authors.lastname: Nair
authors.forename: Filip
authors.initials: F
authors.lastname: Mejza
authors.forename: Wiktoria
authors.initials: W
authors.lastname: Leśniak
authors.forename: Jan
authors.initials: J
authors.lastname: Brozek
authors.forename: Lehana
authors.initials: L
authors.lastname: Thabane
authors.forename: Ji
authors.initials: J
authors.lastname: Cheng
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Bała
authors.forename: Holger J
authors.initials: HJ
authors.lastname: Schünemann
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Sears
authors.forename: Gordon
authors.initials: G
authors.lastname: Guyatt
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D001249:Asthma / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D016001:Confidence Intervals; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects; D000068759:Formoterol Fumarate; D006801:Humans; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic
chemical_list: D000305:Adrenal Cortex Hormones; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D000068759:Formoterol Fumarate