Research in context
Evidence before this study
We searched PubMed up to Jan 16, 2018, for published articles in English addressing the question of long-acting anti-muscarinic (LAMA)–long-acting beta-agonist (LABA) versus LAMA for exacerbations in patients with chronic obstructive pulmonary disease (COPD), using the search terms “COPD”, “chronic obstructive pulmonary disease”, “exacerbation”, “bronchodilator”, “LAMA”, and “LABA”. Previous studies have shown that tiotropium reduces the risk of exacerbation compared with placebo. Although there were several COPD exacerbation trials investigating combinations of bronchodilators, including the SPARK trial (which compared another LAMA–LABA combination with a LAMA and open-label tiotropium), there was no study comparing a combination of a LABA and tiotropium with tiotropium alone that was powered to detect a difference in exacerbations between treatments.
Added value of this study
It has previously been shown that adding olodaterol to tiotropium offers improvements in lung function, symptoms, and quality of life compared with tiotropium alone, without additional safety or tolerability concerns. This large trial is the first of its kind to address the question of whether adding a LABA to tiotropium can offer further benefits in terms of reducing exacerbations in patients with COPD. The findings showed that the reduction in exacerbation rate was smaller than anticipated and did not reach the planned level of significance. However, there were larger improvements in some subgroups of patients, such as those receiving triple therapy at baseline, and in exacerbations that required oral corticosteroids.
Implications of all of the available evidence
Tiotropium–olodaterol offers benefits for patients with COPD beyond those provided by tiotropium alone, which extend to a small reduction in the risk of exacerbations requiring treatment with corticosteroids. This reduction might be larger in certain subgroups of patients.