The IMPACT study recruited patients with symptomatic COPD, and either a forced expiratory volume in 1 second (FEV1) <50% of the predicted normal value and a history of at least one moderate or severe exacerbation in the previous year, or an FEV1 of 50 to 80% and at least two moderate exacerbations or one severe exacerbation in the previous year.
The NICE COPD clinical guideline (published 2010) recommends that:
• A long-acting muscarinic antagonist (LAMA) be offered in addition to long-acting beta agonist (LABA) + inhaled corticosteroid (ICS) to people with COPD who remain breathless or have exacerbations despite taking LABA+ICS, irrespective of their FEV1.
• LABA+ICS in a combination inhaler be considered in addition to LAMA for those with stable COPD who remain breathless or have exacerbations despite LAMA maintenance therapy, irrespective of their FEV1.
In terms of recommendations on use of dual therapy, the guideline states that LAMA can be considered in addition to LABA where ICS is declined or not tolerated. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 Global Strategy for the Diagnosis, Management and Prevention of COPD however recommends LAMA plus LABA the preferred dual therapy for both Group B and Group C patients.
The authors of a related editorial focus on the GOLD recommendations, and the comparison between LAMA plus LABA dual therapy and triple therapy, to address the question of stepping up therapy. They note that the results are difficult to interpret as 40% of patients enrolled were receiving triple therapy at baseline (so randomisation to dual therapy would be a step down of treatment, and would involve abrupt cessation of inhaled corticosteroid), over 70% of patients were receiving an inhaled corticosteroid, and those with a history of asthma were included. The authors of the editorial say this “could explain the rapid surge in exacerbations observed in the first month after randomization in the LAMA–LABA group; during the subsequent 11 months of follow-up, the incidence of exacerbation with LAMA–LABA was practically identical to that with triple therapy”. This may have resulted in a false exaggeration of the effect of triple therapy in comparison to LAMA-LABA.
The editorial calls for further evidence, and until this is available they recommend that clinicians follow the GOLD 2017 guidelines, and only escalate to triple therapy in patients with more symptomatic GOLD group D COPD with frequent exacerbations, when bronchodilator treatment with LAMA–LABA regimens has been maximised.