Safety of formoterol in asthma clinical trials: an update.

Use of long-acting β-agonists (LABAs) in asthma remains controversial, and large safety trials are in progress. We have previously reported safety outcomes with formoterol in 117 AstraZeneca asthma trials (78,339 patients, 92% using inhaled corticosteroids) completed by December 2006, and have now added 32 trials with formoterol (26,124 patients, 100% using inhaled corticosteroids) completed by December 2011. The primary dataset of 79 randomised controlled trials includes 94,684 patients, 67,380 of whom were exposed to formoterol, while the complete dataset comprises 149 trials and 104,463 patients. There were no new asthma-related deaths in the expanded primary dataset, with eight asthma-related deaths among formoterol-randomised patients and two among non-LABA-randomised patients (relative risk 1.13, 95% CI 0.23-10.9), and 15 versus nine cardiac-related deaths (relative risk 0.47, 95% CI 0.19-1.22). Nonfatal asthma-related serious adverse events were significantly reduced with formoterol (relative risk 0.63, 95% CI 0.53-0.75), as were discontinuations due to adverse events. Examining 40 trials with direct formoterol versus non-LABA comparisons, Mantel-Haenszel relative risk for asthma-related death was 2.75 (95% CI 0.52-14.4) and for serious adverse events 0.83 (95% CI 0.68-1.02). We conclude that this enlarged dataset indicates no increased risk of asthma-related deaths among patients exposed to formoterol compared with non-LABA treatments, although the wide confidence interval precludes certainty.