Objective.

—To compare the efficacy and safety of inhaled salmeterol xinafoate, a long-acting β₂-adrenoceptor agonist, with that of albuterol, a short-acting inhaled β₂-agonist, in the treatment of asthma.

Design.

—Randomized, double-blind, placebo-controlled, parallel-group study.

Setting.

—Eleven outpatient clinical centers.

Subjects.

—A total of 322 male and female patients at least 12 years of age with chronic symptomatic asthma requiring daily therapy.

Intervention.

—Patients were treated with salmeterol xinafoate (42 μg inhaled twice daily), albuterol (180 μg inhaled four times daily), or placebo (four times a day) for 12 weeks; patients in all three groups could use inhaled albuterol as backup medication for breakthrough symptoms.

Main Outcome Measures.

—Serial 12-hour forced expiratory flow in 1 second (FEV₁), peak expiratory flow (PEF), asthma symptoms, nocturnal awakenings due to asthma, episodes of asthma exacerbations, and electrocardiography.

Results.

—The mean area under the curve for FEV₁throughout each 12-hour period was consistently greater after a single dose of salmeterol than after two doses of albuterol administered 6 hours apart (P<.001), with the difference ranging from 3.1 to 4.3 L·h. Salmeterol produced an average increase in morning and evening PEF of 26 and 29 L/min, respectively, over pretreatment values compared with decreases of —13 and —3 L/min, respectively, in the albuterol group and —2 L/min both in the morning and evening in the placebo group (P<.001). Patients in the salmeterol group had significantly fewer days and nights with symptoms than did either the albuterol or placebo group (P<.001). Responses to salmeterol were similar at day 1 and at week 12. Adverse events in all treatment groups were equally infrequent, and no clinically significant change in cardiac rhythm was observed with salmeterol treatment.

Conclusion.

—Salmeterol inhaled twice daily is more effective than albuterol inhaled four times a day (or as needed) in patients with asthma requiring maintenance therapy. No deterioration of asthma control was observed with the use of salmeterol over a 3-month period. (JAMA. 1994;271:1412-1416)

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References