SMART assessed the safety of salmeterol (S) added to current asthma therapy in patients naïve to long-acting β-agonists.
This 28-week study compared S 42 mcg bid (MDI) and placebo (P). The primary endpoint was combined number of respiratory-related deaths or life-threatening experiences (intubation and ventilation). Secondary endpoints included asthma-related deaths and combined asthma-related deaths or life-threatening experiences. SMART was stopped in January 2003 following the planned interim analysis due to findings in African Americans (AA) and enrollment difficulties.
A total of 26,353 patients completed the study; S=13,174 and P=13,179. Caucasians (C) comprised 71% of the population compared to 18% in AA. Baseline ICS use was 49% in C and 38% in AA. There was no significant difference in primary outcome (S=48; P=42) or in time to onset of the primary event. No significant differences were seen between S and P in the incidence of any secondary endpoint, with the exception of asthma-related death which occurred rarely and was significantly higher in S vs P (13 vs. 4). AA patients receiving S experienced a higher incidence of asthma-related deaths vs P (8 vs 1); no difference in C (5 vs 2). Asthma-related death was lower in ICS users (6 in 12,254) vs non-ICS users (11 in 14,099) regardless of treatment, and asthma-related deaths occurred more frequently in S who did not use ICS. Similar results occurred in C and AA.CONCLUSIONS: The interim analysis was inconclusive. SMART was not designed to address subpopulation differences. AA race and asthma severity was associated with increased risk of outcomes. Whether outcomes are related to pharmacological, genetic, or factors associated with poor asthma control (ie, delay in seeking medical attention, inadequate use of controller mediations) remains unknown.CLINICAL IMPLICATIONS: Asthma can be a serious and life-threatening disease, and AA have been shown to be at greater risk compared with other ethnic subpopulations. Therefore, asthma management plans and pharmacotherapy should be tailored for individual patients.
All authors are GSK employees.