The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol.
OBJECTIVE
To compare the safety of salmeterol xinafoate or placebo added to usual asthma care.


METHODS
A 28-week, randomized, double-blind, placebo-controlled, observational study.


METHODS
Study subjects were seen once in the study physician's office for screening and were provided all blinded study medication for the entire study period. Follow-up by telephone was scheduled every 4 weeks.


METHODS
Subjects (> 12 years old) with asthma as judged by the study physician were eligible. Individuals with a history of long-acting beta2-agonist use were excluded.


METHODS
Salmeterol, 42 mug bid via metered-dose inhaler (MDI), and placebo bid via MDI.


RESULTS
Following an interim analysis in 26,355 subjects, the study was terminated due to findings in African Americans and difficulties in enrollment. The occurrence of the primary outcome, respiratory-related deaths, or life-threatening experiences was low and not significantly different for salmeterol vs placebo (50 vs 36; relative risk [RR] = 1.40; 95% confidence interval [CI], 0.91 to 2.14). There was a small, significant increase in respiratory-related deaths (24 vs 11; RR, 2.16; 95% CI, 1.06 to 4.41) and asthma-related deaths (13 vs 3; RR, 4.37; 95% CI, 1.25 to 15.34), and in combined asthma-related deaths or life-threatening experiences (37 vs 22; RR, 1.71; 95% CI, 1.01 to 2.89) in subjects receiving salmeterol vs placebo. The imbalance occurred largely in the African-American subpopulation: respiratory-related deaths or life-threatening experiences (20 vs 5; RR, 4.10; 95% CI, 1.54 to 10.90) and combined asthma-related deaths or life-threatening experiences (19 vs 4; RR, 4.92; 95% CI, 1.68 to 14.45) in subjects receiving salmeterol vs placebo.


CONCLUSIONS
For the primary end point in the total population, there were no significant differences between treatments. There were small, but statistically significant increases in respiratory-related and asthma-related deaths and combined asthma-related deaths or life-threatening experiences in the total population receiving salmeterol. Subgroup analyses suggest the risk may be greater in African Americans compared with Caucasian subjects. Whether this risk is due to factors including but not limited to a physiologic treatment effect, genetic factors, or patient behaviors leading to poor outcomes remains unknown.
Nelson
Harold S
HS
National Jewish Medical and Research Center, Denver, CO, USA.
Weiss
Scott T
ST
Bleecker
Eugene R
ER
Yancey
Steven W
SW
Dorinsky
Paul M
PM
D000280:Administration, Inhalation; D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000401:mortality; D002648:Child; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D000068299:Salmeterol Xinafoate; D015996:Survival Rate; D016896:Treatment Outcome
D000318:Adrenergic beta-Agonists; D005938:Glucocorticoids; D000068299:Salmeterol Xinafoate; D000420:Albuterol