Background: Salmeterol is the first long-acting inhaled beta 2-agonist available in the US for the maintenance treatment of asthma.
Objective: To compare the safety of salmeterol with that of the short-acting beta 2-agonist albuterol.
Methods: Two identically designed, prospective, randomized, double-blind, parallel studies were conducted comparing salmeterol 42 micrograms twice daily, albuterol 180 micrograms four times daily, and placebo over 12 weeks in 556 patients (12 to 73 years old) with mild-to-moderate chronic asthma. Patients in each treatment group could use albuterol as needed to control acute symptoms.
Results: The incidence of potentially drug-related adverse events was similar among the treatment groups (range: 22% to 23%), with headache being the most commonly reported (range: 9% to 10%). No deaths occurred during the studies. Concomitant use of > 4 puffs of supplemental albuterol per day in the salmeterol group produced no increase in the incidence of adverse events either in general or of a cardiovascular nature. There were no statistically significant differences among treatment groups or clinically significant changes from pretreatment values in mean pulse rate, systolic/diastolic blood pressure, or clinical laboratory values after 12 weeks. There were no clinically significant differences among groups in heart rates nor were there differences in the frequency of supraventricular or ventricular ectopic beats during 24-hr Holter monitoring. The frequency of asthma exacerbations was lowest among patients receiving salmeterol (and highest among those who received placebo), and this rate did not increase over the 12 weeks. Asthma exacerbations were treated successfully with nebulized albuterol (2.5 mg), with no evidence of any increased risk of cardiovascular events.
Conclusions: Salmeterol 42 micrograms twice daily is well-tolerated in patients with asthma, having a similar safety profile as that of albuterol 180 micrograms inhaled four times daily or placebo (plus as-needed albuterol). Concomitant use of albuterol, either by MDI or nebulization, did not affect the safety of salmeterol. Extensive cardiovascular monitoring revealed no significant cardiovascular adverse effects or arrhythmogenic effects associated with salmeterol over 12 weeks.