The Salmeterol Multicenter Asthma Research Trial

Abstract

Nelson et al1Nelson HS Weiss ST Bleecker ER et al.The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol.Chest. 2006; : 15-26Abstract Full Text Full Text PDF PubMed Scopus (1033) Google Scholar discuss an apparent lower rate of deaths associated with salmeterol in the Salmeterol Multicenter Asthma Research Trial (SMART) [1.22 per 1,000 person-years] compared with the previous UK surveillance study (2.32 per 1,000 person-years).2Castle W Fuller R Hall J et al.Serevent Nationwide Surveillance Study: comparison of salmeterol with salbutamol in asthmatic patients who require regular bronchodilator treatment.BMJ. 1993; 306: 1034-1037Crossref PubMed Scopus (422) Google Scholar However, this low rate cannot be verified from their data. There were 13 deaths in 13,176 salmeterol-treated patients, with median treatment duration of 197 days. Hence, the death rate is (13/13.176) × (365/197), namely 1.83 deaths per 1,000 person-years. Given 22% discontinued prematurely, mean rather than median treatment duration should be the denominator, and so even 1.83 deaths per 1,000 person-years is an underestimate of the true risk. It is unclear how Nelson et al1Nelson HS Weiss ST Bleecker ER et al.The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol.Chest. 2006; : 15-26Abstract Full Text Full Text PDF PubMed Scopus (1033) Google Scholar calculated the risk of 1.22 per 1,000 person-years (see page 25 of their report). Does this rate refer to white patients only? Six deaths among 9,281 white patients gives (6/9.281) × (365/197) or 1.20 deaths per 1,000 person-years. If so, the calculation for African-American patients should also be reported, namely (7/2.366) × (365/197) or 5.48 deaths per 1,000 person-years. Ages at death in the salmeterol-treated patients were 14, 37, 41, 46, 46, 47, 47, 51, 56, 56, 60, 62, and 67 years, similar to those deaths in the UK study.3Fuller RW Castle WM Hall JR et al.Bronchodilator treatment in asthma [letter].BMJ. 1993; 306: 1611Crossref Google Scholar The true comparators for these study populations are death rates for their age group, not for the total population, as most asthma deaths occur in the elderly.4Sears MR Taylor DR Bronchodilator treatment in asthma [letter].BMJ. 1993; 307: 446Crossref PubMed Google Scholar In the United States from 1990 to 2001, mortality from asthma as the underlying cause of death in the population aged 45 to 64 years (the majority of those dying in the SMART) was 2.4 per 100,000.5Mc Coy L Reddelings M Sorvillo F et al.A multiple cause-of-death analysis of asthma mortality in the United States, 1990–2001.J Asthma. 2005; 42: 757-763Crossref PubMed Scopus (60) Google Scholar Using a conservative 5% prevalence for adult asthma, this translates to a rate of 0.48 per 1,000 person-years. Hence, the death rate in the SMART is approximately fourfold higher than would be expected in the US asthmatic population of that age. To the EditorCHESTVol. 130Issue 3PreviewWe appreciate Dr. Sears' comment regarding the asthma-related death rate for salmeterol recipients in the Salmeterol Multicenter Asthma Research Trial (SMART). In the “Discussion” section, we inadvertently listed the asthma death rate for the total population (1.22 per 1,000 person-years). The asthma death rate for subjects exposed to salmeterol in SMART was 1.98 per 1,000 person-years. However, the conclusions regarding the asthma death rate with regard to Castle et al1 and Martin and Shakir2 remain unchanged. Full-Text PDF