Cardiovascular safety of long acting beta agonist-inhaled corticosteroid combination products in adult patients with asthma: a systematic review

Lung. 2014 Feb;192(1):47-54. doi: 10.1007/s00408-013-9525-x. Epub 2013 Oct 24.

Abstract

Introduction: 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.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / administration & dosage
  • Adrenal Cortex Hormones / adverse effects*
  • Adrenergic beta-Agonists / administration & dosage
  • Adrenergic beta-Agonists / adverse effects*
  • Adult
  • Anti-Asthmatic Agents / administration & dosage
  • Anti-Asthmatic Agents / adverse effects*
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / adverse effects*
  • Asthma / diagnosis
  • Asthma / drug therapy*
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / adverse effects*
  • Cardiovascular Diseases / chemically induced*
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / epidemiology
  • Drug Combinations
  • Humans
  • Incidence
  • Odds Ratio
  • Patient Safety
  • Risk Assessment
  • Risk Factors
  • Treatment Outcome

Substances

  • Adrenal Cortex Hormones
  • Adrenergic beta-Agonists
  • Anti-Asthmatic Agents
  • Anti-Inflammatory Agents
  • Bronchodilator Agents
  • Drug Combinations