title: Inhaled Long-Acting β2-Agonists Do Not Increase Fatal Cardiovascular Adverse Events in COPD: A Meta-Analysis.
abstract: BACKGROUND
  The cardiovascular safety of inhaled long-acting β2-agonists (LABAs) in patients with chronic obstructive pulmonary disease (COPD) is a controversial problem. Certain studies have suggested that inhaled LABAs lead to an increased risk of cardiovascular events in patients with COPD. This meta-analysis aimed to assess the cardiovascular safety of inhaled LABAs in COPD.
  
  
  METHODS
  A meta-analysis of randomized, double-blind, parallel-group, placebo-controlled trials for LABA treatment of COPD with at least 3 months of follow-up was performed. The fixed-effects model was used to evaluate the effects of LABAs on fatal cardiovascular adverse events. Adverse events were collected for each trial, and the relative risk (RR) and 95% confidence intervals (CI) for LABA/placebo were estimated.
  
  
  RESULTS
  There were 24 trials included in this meta-analysis. Compared with placebo, inhaled LABAs significantly decreased fatal cardiovascular adverse events in COPD patients (RR 0.65, 95% CI 0.50 to 0.86, P = 0.002). In sensitivity analysis, there was still no increased risk of fatal cardiovascular events (RR 0.68, 95%CI 0.46 to 1.01, P = 0.06) after excluding the trial with the largest weight. Among the different types of LABAs, only salmeterol had a significant effect (RR 0.64, 95% CI 0.46 to 0.90). In subgroup analyses, inhaled LABAs were able to significantly decrease fatal cardiovascular events in long-term trials (RR 0.64, 95% CI 0.47 to 0.87) and in trials with severe COPD patients (RR 0.69, 95% CI 0.50 to 0.96).
  
  
  CONCLUSIONS
  Inhaled LABAs do not increase the risk of fatal cardiovascular events in COPD patients.
authors.affiliation: Department of Respiratory Diseases, Xuanwu Hospital, Capital Medical University, Beijing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Xia
authors.affiliation: Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Respiratory Diseases, Xuanwu Hospital, Capital Medical University, Beijing, China.
authors.forename: Xiuhong
authors.initials: X
authors.lastname: Nie
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects*; D001993:Bronchodilator Agents / Q000008:administration & dosage; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D004311:Double-Blind Method; D006801:Humans; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D000068299:Salmeterol Xinafoate / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D000068299:Salmeterol Xinafoate