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Fewer exacerbations but somewhat more pneumonia with triple inhaler therapy for COPD (IMPACT)
Clinical Question
Which combination is best for patients with at least moderate COPD: a long-acting beta-agonist plus a long-acting muscaranic antagonist plus a steroid; LABA plus LAMA; or LABA plus a steroid?
Bottom line
This study found that 1000 patients treated for one year with LABA plus LAMA plus steroid (triple therapy) would have 96 pneumonias and 923 exacerbations; those given LABA plus steroid would have 97 pneumonias and 1052 exacerbations; and those given LABA plus LAMA would have only 61 pneumonias but would have 1150 exacerbations. Thus, for every 8 exacerbations prevented by using triple therapy, there is approximately one additional pneumonia compared with LAMA plus LABA treatment. A methodologic concern (in addition to the relatively high dropout rate) was the fact that many patients were using a steroid inhaler at study entry, and the inhaler was withdrawn if they were assigned to the LAMA plus LABA group, which could lead to a higher risk of exacerbations. 1b
Reference
Study design: Randomized controlled trial (double-blinded)
Funding: Industry
Setting: Outpatient (any)
Synopsis
In this industry-sponsored trial, the researchers identified 10,355 patients with chronic obstructive pulmonary disease (COPD) who met the following criteria: 40 years or older, symptomatic COPD, and either an FEV1 of less than 50% of predicted and at least one moderate or severe exacerbation in the previous year, or an FEV1 of 50% to 80% and at least 2 moderate or one severe exacerbation in the previous year. Patients were randomized into 1 of 3 groups in a 2:2:1 ratio: (1) a LABA (vilanterol 25 mcg) plus a LAMA (umeclidinium 62.5 mcg) plus a glucocorticoid (fluticasone furoate 100 mcg); (2) the LABA plus glucocorticoid; or (3) the LABA plus LAMA. All combinations used identical doses of the study medications, and inhalers were used once daily. Clinician judgment was used to label an event as either pneumonia or COPD exacerbation, although radiographs were required when pneumonia was suspected. Patients kept a symptom diary, and reported any worsening of symptoms, with the severity classified according to the need for additional treatment. A moderate exacerbation was defined as one requiring treatment with antibiotics or systemic steroids, while a severe exacerbation was one resulting in hospitalization or death. The patients' mean age was 65 years, 66% were men, and 77% completed the one-year study while using the assigned inhaler. Patients assigned to triple therapy had significantly fewer exacerbations than those in either of the dual therapy groups (0.91 vs 1.07 for LABA plus steroid and 1.21 for LABA plus LAMA; P < .001 for comparison of triple therapy to each dual therapy inhaler). All groups had small improvements in health-related quality of life during the study period, but the difference between groups was not clinically meaningful (< 2 points on a 100-point scale). There were no differences between groups regarding adverse events, although patients in the groups that received an inhaled steroid had a higher risk of pneumonia during the study period (96 vs 61 per 1000 person-years).
Reviewer
Mark H. Ebell, MD, MS
Professor
University of Georgia
Athens, GA
Comments
Very handy stat to use when discussing pros and cons of steroid puffers w COPD pts. Just what I needed! Hear the methodological concerns tho.
see response to Q1
Good poem
there is considerable debate as to whether the study included patients with asthma.
This is an industry based study with some methodoligical problems.