Chest
Volume 123, Issue 6, June 2003, Pages 1817-1824
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Clinical Investigations
COPD
Cardiovascular Safety of Salmeterol in COPDa

https://doi.org/10.1378/chest.123.6.1817Get rights and content

Background

Patients with COPD have an increased risk of cardiovascular disease. Despite the clinical benefits of long-acting β-agonist agents in the treatment of COPD, patients may be at an increased risk of cardiovascular toxicity, including tachyarrhythmia due to β-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 μg 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 μg bid. The median duration of treatment was 24 weeks (range, 12 to 52 weeks).

Results

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

Section snippets

Materials and Methods

A pooled analysis of cardiovascular safety data was conducted to assess the effects of therapy with salmeterol, 50 μg bid, on the cardiovascular system in patients with COPD. In order to conduct a pooled analysis, individual patient data are required. A total of 17 clinical studies of salmeterol treatment in COPD patients were considered for inclusion because of the availability of individual patient data. Further prospectively defined inclusion criteria included the following: sponsorship by

Results

A total of 1,443 patients received placebo, while 1,410 patients were treated with salmeterol, 50 μg bid. The data are presented only for the ITT population since the findings in the PR population were similar to those in the ITT population. Although some differences were observed among subgroups when compared to the overall ITT population (data for these differences are presented), the findings across subgroups were comparable between the salmeterol and placebo groups. Only significant results

Discussion

Traditionally, treatment options have been fairly limited for patients with COPD. However, the use of salmeterol, a relatively new agent that has been indicated for the treatment of COPD, has resulted in considerable clinical benefits. Significant improvements in lung function, dyspnea ratings, and exercise performance have been reported in patients with COPD treated with salmeterol.461314In one comparative study6with ipratropium bromide, salmeterol significantly reduced the time to first

Acknowledgment

We thank Tracy Weeks and Shehnaz Gangjee, PhD, for assistance with the preparation of this manuscript.

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Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: [email protected]).

The studies reported in this manuscript were supported by GlaxoSmithKline.

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