Salmeterol Xinafoate as Maintenance Therapy Compared With Albuterol in Patients With Asthma

Abstract

<h3>Objective.</h3> —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. <h3>Design.</h3> —Randomized, double-blind, placebo-controlled, parallel-group study. <h3>Setting.</h3> —Eleven outpatient clinical centers. <h3>Subjects.</h3> —A total of 322 male and female patients at least 12 years of age with chronic symptomatic asthma requiring daily therapy. <h3>Intervention.</h3> —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. <h3>Main Outcome Measures.</h3> —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. <h3>Results.</h3> —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 (<i>P</i>&lt;.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 (<i>P</i>&lt;.001). Patients in the salmeterol group had significantly fewer days and nights with symptoms than did either the albuterol or placebo group (<i>P</i>&lt;.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. <h3>Conclusion.</h3> —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. (<i>JAMA</i>. 1994;271:1412-1416)