Current issues of ACP Journal Club are published in Annals of Internal Medicine


Salmeterol was more effective than albuterol in reducing symptoms in asthma

ACP J Club. 1994 Sept-Oct;121:35. doi:10.7326/ACPJC-1994-121-2-035

Source Citation

D'Alonzo GE, Nathan RA, Henochowicz S, et al. Salmeterol xinafoate as maintenance therapy compared with albuterol in patients with asthma. JAMA. 1994 May 11;271:1412-6.



To compare the effectiveness and safety of inhaled salmeterol xinafoate with albuterol in patients with chronic symptomatic asthma.


Randomized, double-blind, placebo-controlled trial with 12-week follow-up.


11 outpatient clinical centers.


322 patients (mean age 29 y, 65% men) with chronic symptomatic asthma requiring daily drug treatment for at least 6 months before study entry. Exclusion criteria were age < 12 years and current smoking. 280 patients (87%) completed the study.


Patients were allocated to receive salmeterol xinafoate, 42 µg inhaled twice daily (n = 106); albuterol, 180 µg inhaled 4 times daily (n = 108); or placebo, 4 times daily (n = 108) for 12 weeks. All patients could use inhaled albuterol as backup medication for breakthrough symptoms.

Main outcome measures

Serial 12-hour forced expiratory volume in 1 second (FEV1) at weeks 1, 4, 8, and 12; peak expiratory flow (PEF); asthma symptoms; asthma exacerbations; and adverse effects.

Main results

The mean area-under-the-curve for FEV1 throughout 12 hours was greater in the salmeterol group than in the albuterol group, with the difference ranging from 3.1 to 4.3 litre-hours (L·h) (P < 0.001). Salmeterol produced a mean increase in morning and evening PEF of 26 and 29 L/min, respectively, over baseline values compared with decreases of 13 and 3 L/min, respectively, in the albuterol group and 2 L/min for morning and evening PEF in the placebo group (P < 0.001). Patients receiving salmeterol had fewer days and nights with symptoms than either the albuterol or placebo groups (P < 0.001). No difference in the frequency or type of adverse effects was noted among the 3 treatment groups.


Inhaled salmeterol xinafoate was more effective than albuterol in increasing morning and evening peak flow, in increasing forced expiratory volume in 1 second, and in reducing day and night asthma symptoms in patients with chronic symptomatic asthma.

Source of funding: Glaxo Inc.

For article reprint: Dr. G.E. D'Alonzo, Pulmonary Disease Division, Temple University School of Medicine, 3401 North Broad Street, Philadelphia, PA 19140, USA. FAX 215-707-6867.


The study by D'Alonzo and colleagues fuels the controversy surrounding the appropriate use of selective β2-agonists. Recent concerns about increasing prevalence and morbidity from asthma have demanded a reassessment of our current therapeutic regimens. Advances in the understanding of the pathogenesis of asthma have suggested that in many patients, attention must be directed at the underlying inflammatory processes. Thus, it has been proposed that if short-acting bronchodilators are required on a regular basis, indicating that the inflammatory process has become well established, appropriate care would include the use of an additional agent, such as inhaled steroids, cromolyn, or nedocromil (1).

The importance of supplemental medications is underlined in this study. 74% of patients receiving salmeterol, 75% receiving placebo, and 80% receiving albuterol were routinely also receiving inhaled steroids, theophylline, or cromolyn. Only 15 patients were forced to withdraw because of increasing symptoms, 5 in each group. Information about supplemental medications in these patients and in those who had exacerbations was not provided.

The results suggest that the long-acting β2-agonist, salmeterol, in combination with additional therapeutic agents, may provide more stable pulmonary function and may contribute to a decrease in daytime and nighttime symptoms. Whether this medication should be used alone for the treatment of asthma, however, is not as well defined. In addition, reducing a patient's medications to the smallest amount that satisfactorily controls symptoms should be the goal of all physicians who care for patients with asthma. Long-acting β2-agonists may not allow for the finer control of more sophisticated management. Finally, it must be reiterated that salmeterol should not be used for acute exacerbations of asthma nor should increased dosing be tried for increasing symptoms. Short-acting β2-agonists must be supplied for use during these situations.

Bernard Adelsberg, MD
Yale New Haven HospitalNew Haven, Connecticut, USA


1. Guidelines for the Diagnosis and Management of Asthma. Bethesda, Maryland: National Asthma Education Program; 1991. NIH publication 91-3042.