There has been an increase in the types and numbers of inhaler devices and medications available for COPD maintenance therapy, which has caused confusion in some specialists, GPs and patients alike. However, the classes of inhaled medications have not changed: short-acting beta2-agonists (SABA), long-acting beta2-agonists (LABA), short-acting muscarinic antagonists (SAMA), long-acting muscarinic antagonists (LAMA) and inhaled corticosteroids (ICS). Within these classes of inhaled medications, many options are now available; however, meta-analyses to date have not shown any statistically significant differences among LAMAs in preventing moderate-to-severe exacerbations of COPD.10 Comparisons within other classes appear limited at present.
When considering treatment for an individual patient, factors to consider include the patient’s symptoms, COPD severity and comorbidities, and the type of inhaler device to use. Combining two medications of the same class, such as a LABA/LAMA or LABA/ICS combination and an additional LABA is not advised; the risk of side effects is increased for no added symptomatic improvement.
Inhaler technique is often suboptimal, including in those who are long-term inhaler users. Use of multiple inhaler device types is associated with an increase in errors and may be associated with a poorer outcome in patients with COPD. Therefore, frequent review of inhaler technique and rationalisation of device type is beneficial.12,13
SABA and SAMA
Short-acting bronchodilators, such as the SABA salbutamol or the SAMA ipratropium bromide, can be used as as-needed therapy for patients with only occasional dyspnoea. SABAs can be given for immediate relief of symptoms in patients already using a long-acting bronchodilator for maintenance therapy. SABAs and SAMAs can improve lung function and dyspnoea. Side effects are generally minor; however, a meta-analysis of randomised controlled trials, and a later cohort study, found an increased risk of adverse cardiovascular events with ipratropium bromide.14 This has not been seen with tiotropium.15,16
LAMA, LABA and LAMA/LABA combinations
Patients who need more than occasional use of short-acting bronchodilators may be started on a single long-acting bronchodilator, either a LAMA or LABA. A recent meta-analysis comparing LABAs with LAMAs assessed 16 randomised double-blinded controlled trials of patients with moderate-to-very-severe COPD.17 It found that LAMAs were associated with a lower risk of acute exacerbations and lower incidence of adverse events, compared with LABAs. No significant differences between LAMAs and LABAs were found in terms of changes in lung function, symptoms or health status. LAMAs may be preferable to LABAs in patients with stable COPD, especially those at risk of frequent exacerbations.17
In patients with persistent dyspnoea on one bronchodilator treatment, a second bronchodilator should be added.5 Several LAMA/LABA fixed-dose combinations delivered in a single inhaler are available in Australia, via a range of devices. A network meta-analysis of LAMA/LABA combinations compared with the individual monotherapies found that the fixed-dose combinations provided benefits in lung function and quality of life, with no increase in adverse outcomes.18 Combination therapy reduced moderate-to-severe exacerbations compared with a LABA alone but not compared with a LAMA alone. Effects on severe exacerbations were similar with both combination and monotherapies. Other network meta-analyses have also found benefits for LAMA/LABA fixed-dose combinations, compared with their monocomponents.19 PBS requirements for these medications should be taken into consideration.