As early as 2003, the concerns about the safety of long-acting β-agonists led the U.S. Food and Drug Administration to require GlaxoSmithKline (Research Triangle Park, North Carolina) to conduct a very large (>26 000 persons), postmarketing, randomized, controlled trial to examine drug safety (7). The SMART (Salmeterol Multicenter Asthma Research Trial) was a randomized, double-blind, placebo-controlled study of drug safety under a “real-world,” effectiveness study design based in the United States. The study allowed concomitant use of inhaled corticosteroids. GlaxoSmithKline ended the study because of preliminary findings and difficulties in reaching target enrollment and published the results in 2006. The trial found no statistically significant differences between treatments in the combined end point that included respiratory-related deaths and life-threatening experiences. However, the individual clinical end points of respiratory-related and asthma-related deaths were statistically significantly increased in persons receiving salmeterol, and the time to first serious event was slightly shorter (8). Moreover, a post hoc subgroup analysis strongly suggested that the risk may be greater in African Americans.