The safety of formoterol among patients with asthma using inhaled corticosteroids. Systematic review and meta-analysis.

INTRODUCTION: It has been postulated that inhaled long acting beta-agonists (LABAs) when used as monotherapy in asthma may increase the incidence of asthma related deaths, intubations and hospitalizations, but concomitant use of inhaled corticosteroids (ICS) may modify this effect. OBJECTIVES: To assess the safety of formoterol in patients with asthma using ICS. PATIENTS AND METHODS: We conducted a systematic review and meta-analysis of parallel group, blinded, randomized controlled trials with at least 12 weeks of treatment examining the impact of twice a day formoterol on asthma-related and total morbidity and mortality in patients concurrently using ICS. Our main analysis considering impact of LABAs (salmeterol and formoterol) has already been published. In this report we present detailed information from studies investigating use of twice daily formoterol among patients receiving ICS. RESULTS: The search yielded 16 relevant studies included in this analysis. Among over 10,000 participants (5,996 taking formoterol with over 4,000 patient-years observation in formoterol groups) there were 2 asthma-related deaths (both in formoterol groups) and no asthma-related non-fatal intubations. The risk of asthma-related hospitalizations (odds ratio [OR] 0.59, 95% CI 0.37-0.93) and asthma-related serious adverse events (mostly hospitalizations) [OR 0.58, 95% CI 0.37-0.91] were significantly lower in patients on formoterol and ICS compared to patients on ICS alone. The OR for total mortality was 1.22, 95% CI 0.38-3.90, reflecting 7 deaths in formoterol groups and 3 deaths in control groups respectively. CONCLUSIONS: In patients with asthma using inhaled corticosteroids formoterol decreased the risk of asthma-related hospitalizations. There were too few asthma-related deaths and intubations to establish formoterol's relative impact on these outcomes.