Pharmacoepidemiological Study of Long-Acting β-agonist/Inhaled Corticosteroid Therapy and Asthma Mortality: Clinical Implications.

RATIONALE: The increased risk of asthma mortality in association with long-acting β2-agonist (LABA) monotherapy is well documented but the risk associated with LABA plus inhaled corticosteroid (ICS) therapy remains unclear.

OBJECTIVE: We assessed the feasibility of a large pharmacoepidemiological study to compare the effect of combined LABA + ICS therapy with non-LABA maintenance therapy on the risk of asthma mortality.

METHODS: This observational retrospective study used electronic data from ten US data partners to construct a cohort of patients with persistent asthma (defined as: four or more asthma maintenance medication dispensings in 12 months and a code diagnosis of asthma). Asthma deaths were determined by linking patient data with the National Death Index.

RESULTS: From 5,881,438 asthma patients, a cohort of 994,627 met the criteria for persistent asthma and provided 2.4 million person-years of follow-up. The total number of deaths was 278 with only three of these occurring after incident exposure to an asthma maintenance medication. The overall pooled asthma mortality rate, standardized by age and data partner, was 1.16 [95 % confidence interval (CI) 0.98-1.34] per 10,000 person-years; crude mortality rates (per 10,000 person-years) increased with age and were higher in female individuals (1.34; 95 % CI 1.15-1.55) than in male individuals (0.92; 95 % CI 0.74-1.12).

CONCLUSIONS: Despite a cohort size of almost 1 million asthma patients, the asthma mortality risk associated with combined LABA + ICS therapy could not be determined. This study showed that very few patients with persistent asthma have asthma-related deaths, and confirmed that those who die are more likely to be older and female.