Cardiovascular safety of salmeterol in COPD

Chest. 2003 Jun;123(6):1817-24. doi: 10.1378/chest.123.6.1817.


Background: Patients with COPD have an increased risk of cardiovascular disease. Despite the clinical benefits of long-acting beta-agonist agents in the treatment of COPD, patients may be at an increased risk of cardiovascular toxicity, including tachyarrhythmia due to beta-adrenergic stimulation.

Objective: To evaluate the cardiovascular safety of salmeterol in COPD patients by conducting a pooled analysis of cardiovascular safety data.

Design: Randomized, double-blind, parallel group, multiple-dose studies, which included salmeterol, 50 micro g bid, and placebo arms.

Study selection: Seven of a total of 17 studies met the predefined inclusion requirements and were pooled. A total of 1,443 patients received placebo, while 1,410 patients received salmeterol, 50 micro g bid. The median duration of treatment was 24 weeks (range, 12 to 52 weeks).

Results: Treatment with salmeterol, 50 micro g bid, showed no increased risk of cardiovascular adverse events (AEs) compared with placebo (relative risk, 1.03; 95% confidence interval, 0.8 to 1.3; p = 0.838). Both groups had a similar incidence of cardiovascular events (8%), including cardiovascular deaths. The incidence of cardiovascular AEs increased with age, concurrent cardiovascular conditions, and treatment with antiarrhythmic/bradycardic agents, although increases were comparable in both treatment groups. There were no episodes of sustained ventricular tachycardia, and no clinically significant differences were observed in 24-h heart rate, ventricular and supraventricular ectopic events, qualitative ECGs, QT intervals, or vital signs between the salmeterol, 50 micro g bid, group and the placebo group. Similar findings were observed when patients were stratified for age of > 65 years or the known presence of cardiovascular disease.

Conclusions: Treatment with salmeterol, 50 micro g bid, does not increase the risk of cardiovascular AEs in this population of COPD patients compared with placebo.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / administration & dosage
  • Adrenergic beta-Agonists / adverse effects*
  • Aged
  • Albuterol / administration & dosage
  • Albuterol / adverse effects*
  • Albuterol / analogs & derivatives*
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / adverse effects*
  • Cardiovascular Diseases / chemically induced
  • Cardiovascular System / drug effects*
  • Double-Blind Method
  • Electrocardiography
  • Electrocardiography, Ambulatory
  • Female
  • Humans
  • Male
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Salmeterol Xinafoate
  • Tachycardia / chemically induced


  • Adrenergic beta-Agonists
  • Bronchodilator Agents
  • Salmeterol Xinafoate
  • Albuterol