Salmeterol xinafoate as maintenance therapy compared with albuterol in patients with asthma

JAMA. 1994 May 11;271(18):1412-6.


Objective: To compare the efficacy and safety of inhaled salmeterol xinafoate, a long-acting beta 2-adrenoceptor agonist, with that of albuterol, a short-acting inhaled beta 2-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 micrograms inhaled twice daily), albuterol (180 micrograms 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 FEV1 throughout 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adrenergic beta-Agonists / administration & dosage
  • Adrenergic beta-Agonists / therapeutic use*
  • Adult
  • Albuterol / administration & dosage
  • Albuterol / analogs & derivatives*
  • Albuterol / therapeutic use*
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / therapeutic use*
  • Chronic Disease
  • Circadian Rhythm
  • Double-Blind Method
  • Drug Administration Schedule
  • Electrocardiography
  • Electrocardiography, Ambulatory
  • Female
  • Forced Expiratory Volume
  • Humans
  • Male
  • Peak Expiratory Flow Rate
  • Respiratory Function Tests
  • Salmeterol Xinafoate


  • Adrenergic beta-Agonists
  • Bronchodilator Agents
  • Salmeterol Xinafoate
  • Albuterol