Cardiovascular safety of salmeterol in COPD.
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.


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


METHODS
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.
Ferguson
Gary T
GT
Pulmonary Research Institute of SouthEast Michigan, Livonia, MI 48152, USA.
Funck-Brentano
Christian
C
Fischer
Tracy
T
Darken
Patrick
P
Reisner
Colin
C
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000009:adverse effects*; D000368:Aged; D000420:Albuterol / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced; D002319:Cardiovascular System / Q000187:drug effects*; D004311:Double-Blind Method; D004562:Electrocardiography; D015716:Electrocardiography, Ambulatory; D005260:Female; D006801:Humans; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D000068299:Salmeterol Xinafoate; D013610:Tachycardia / Q000139:chemically induced
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D000068299:Salmeterol Xinafoate; D000420:Albuterol