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Am Fam Physician. 2004;69(3):704

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. To reduce the impact of this disease on patients, the Global Initiative for Chronic Obstructive Lung Disease study attempted to increase awareness of COPD and decrease the morbidity and mortality related to this disease. Bronchodilators are the only agents approved by the U.S. Food and Drug Administration for treatment of COPD. The bronchodilator salmeterol, a long-acting beta2-adrenergic agonist, has an approximate duration of 12 hours and improves airflow obstruction. The use of salmeterol has been shown to improve symptoms, lung function, and quality of life in patients with COPD; it is recommended as a first-line maintenance bronchodilator in patients with this disease. However, patients with COPD tend to have ischemic heart disease, right ventricular hypertrophy, and arrhythmias, and long-acting beta2-agonists may increase the risk of cardiovascular complications. Ferguson and associates examined the cardiovascular safety of salmeterol in patients with COPD in a study sponsored by a pharmaceutical company.

The study design was a pooled analysis of cardiovascular safety data in COPD patients taking salmeterol in a dosage of 50 mcg twice per day. The studies included were randomized, double-blinded, parallel-group, multi-dose trials of salmeterol at 50 mcg administered with a metered-dose inhaler. Patients met the diagnostic criteria for COPD established by the American Thoracic Society or the European Respiratory Society. Seven studies monitoring vital signs and cardiovascular adverse events met the inclusion criteria. Participants were grouped by age and concurrent cardiovascular conditions, and whether they were taking antiarrhythmic or bradycardic medications.

A total of 1,410 patients took salmeterol, and 1,443 took placebo. There was no increase in the risk of cardiovascular adverse events in patients taking salmeterol compared with placebo; the incidence of cardiovascular events was 8 percent in both groups. Patients who had concurrent cardiovascular conditions and were older or taking antiarrhythmic or bradycardic medications had a higher incidence of cardiovascular adverse events, but the rate was similar between treatment groups. There also was no difference between groups with regard to 24-hour heart rate, ventricular and supraventricular ectopic events, qualitative electrocardiograms, QT intervals, or vital signs.

The authors conclude that, compared with placebo, treating patients who have COPD with salmeterol in a dosage of 50 mcg twice a day does not increase the risk for cardiovascular adverse events. They add that salmeterol can be used safely to manage COPD symptoms, improve lung function, potentially decrease exacerbations, and improve quality of life.

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