Impact of triple therapy on mortality in COPD

Only a few therapies have been shown to prolong survival in specific patients with COPD. In recent years, the IMPACT and the ETHOS trials suggested that triple therapy (a combination of inhaled corticosteroid (ICS), long-acting muscarinic antagonist (LAMA) and long-acting β₂-agonist (LABA) given in a single inhaler) may reduce mortality compared with dual bronchodilation. These results need however to be interpreted with caution. These trials were not powered by design to evaluate the impact of triple therapy on mortality as mortality was a secondary outcome. In addition, mortality reduction has to be put in perspective with the low mortality rate in both studies (<2%). Furthermore, a key methodological issue is that up to 70-80% of patients had ICS withdrawal at the enrolment in the LABA/LAMA arms, but none in the ICS-containing treatment arms. It is possible that ICS withdrawal may have contributed to some early death events. Finally, the inclusion and exclusion criteria of both trials were designed to select patients likely to respond to ICS. There are no conclusive data yet that triple therapy reduces mortality in COPD. Future, well-designed and -powered trials are needed to validate the findings on mortality.