title: Cardiovascular safety of long acting beta agonist-inhaled corticosteroid combination products in adult patients with asthma: a systematic review.
abstract: BACKGROUND
  Long-acting beta agonists and inhaled corticosteroids combination products (LABA-ICS) are widely used in the treatment of asthma. However, there appears to be little data on their cardiovascular safety. The purpose of this study was to conduct a systematic review of the available studies and trials on the cardiovascular safety of LABA-ICS in adults with asthma.
  
  
  METHODS
  Two independent reviewers screened citations from PubMed and National Clinical Trials registry to identify studies and trials on the cardiovascular effects of LABA-ICS in patients with asthma.
  
  
  RESULTS
  A total of 15 studies (with 17 cohorts on LABA-ICS to compare with a comparator or placebo) with 5,440 total study participants met the inclusion criteria. Two studies on budesonide-formoterol and one on fluticasone-salmeterol reported treatment emergent cardiovascular adverse events, all of which were dysrhythmias. For comparison, the pooled estimate of the Peto odds ratio (0.72; 95 % confidence interval [CI] 0.17-3; p = 0.65) and the summary risk ratio (0.77; 95 % CI 0.26-2.3; p = 0.64) indicated a nonsignificant difference between LABA-ICS and comparator/placebo groups.
  
  
  CONCLUSIONS
  Our systematic review found that few studies and trials reported treatment emergent cardiovascular adverse events with LABA-ICS. However, the Peto odds ratio and risk ratio for these outcomes was statistically nonsignificant. This suggests that LABA-ICS products may have a safe cardiovascular profile in asthma patients.
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of South Carolina, 1 Medical Park, Suite 300, Columbia, SC, 29203, USA, imran.iftikhar@uscmed.sc.edu.
authors.forename: Imran H
authors.initials: IH
authors.lastname: Iftikhar
authors.forename: Muhammad
authors.initials: M
authors.lastname: Imtiaz
authors.forename: Allan S
authors.initials: AS
authors.lastname: Brett
authors.forename: David J
authors.initials: DJ
authors.lastname: Amrol
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000009:adverse effects*; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000009:adverse effects*; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D004338:Drug Combinations; D006801:Humans; D015994:Incidence; D016017:Odds Ratio; D061214:Patient Safety; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D004338:Drug Combinations