Long‐acting beta2‐agonist in addition to tiotropium versus either tiotropium or long‐acting beta2‐agonist alone for chronic obstructive pulmonary disease
Abstract
Background
Long‐acting bronchodilators comprising long‐acting beta2‐agonists and the anticholinergic agent tiotropium are commonly used for managing persistent symptoms of chronic obstructive pulmonary disease. Combining these treatments, which have different mechanisms of action, may be more effective than the individual components. However, the benefits and risks of combining tiotropium and long‐acting beta2‐agonists for the treatment of chronic obstructive pulmonary (COPD) disease are unclear.
Objectives
To assess the relative effects of treatment with tiotropium in addition to long‐acting beta2‐agonist compared to tiotropium or long‐acting beta2‐agonist alone in patients with chronic obstructive pulmonary disease.
Search methods
We searched the Cochrane Airways Group Specialised Register of trials and clinicaltrials.gov up to January 2012.
Selection criteria
We included parallel group, randomised controlled trials of three months or longer comparing treatment with tiotropium in addition to long‐acting beta2‐agonist against tiotropium or long‐acting beta2‐agonist alone for patients with chronic obstructive pulmonary disease.
Data collection and analysis
Two review authors independently assessed trials for inclusion and then extracted data on trial quality and the outcome results. We contacted study authors for additional information. We collected information on adverse effects from the trials.
Main results
Five trials were included in this review, mostly recruiting participants with moderate or severe chronic obstructive pulmonary disease. All of them compared tiotropium in addition to long‐acting beta2‐agonist to tiotropium alone, but only one trial additionally compared a combination of the two types of bronchodilator with long‐acting beta2‐agonist (formoterol) alone. Two studies used the long‐acting beta2‐agonist indacaterol, two used formoterol and one used salmeterol.
Compared to tiotropium alone (3263 patients), treatment with tiotropium plus long‐acting beta2‐agonist resulted in a slightly larger improvement in the mean health‐related quality of life (St George's Respiratory Questionnaire (SGRQ) MD ‐1.61; 95% CI ‐2.93 to ‐0.29). In the control arm, tiotropium alone, the SGRQ improved by falling 4.5 units from baseline and with both treatments the improvement was a fall of 6.1 units from baseline (on average). High withdrawal rates in the trials increased the uncertainty in this result, and the GRADE assessment for this outcome was therefore moderate. There were no significant differences in the other primary outcomes (hospital admission or mortality).
The secondary outcome of pre‐bronchodilator FEV1 showed a small mean increase with the addition of long‐acting beta2‐agonist (MD 0.07 L; 95% CI 0.05 to 0.09) over the control arm, which showed a change from baseline ranging from 0.03 L to 0.13 L on tiotropium alone. None of the other secondary outcomes (exacerbations, symptom scores, serious adverse events, and withdrawals) showed any statistically significant differences between the groups. There were wide confidence intervals around these outcomes and moderate heterogeneity for both exacerbations and withdrawals.
The results from the one trial comparing the combination of tiotropium and long‐acting beta2‐agonist to long‐acting beta2‐agonist alone (417 participants) were insufficient to draw firm conclusions for this comparison.
Authors' conclusions
The results from this review indicate a small mean improvement in health‐related quality of life for patients on a combination of tiotropium and long‐acting beta2‐agonist compared to tiotropium alone, but it is not clear how clinically important this mean difference may be. Hospital admission and mortality have not been shown to be altered by adding long‐acting beta2‐agonists to tiotropium as there were not enough data to determine the relative efficacy and safety of tiotropium plus long‐acting beta2‐agonist compared to long‐acting beta2‐agonist alone. There were insufficient data to make comparisons between the different long‐acting beta2‐agonists when used in addition to tiotropium.
PICOs
Plain language summary
Is it better to take a combination of tiotropium and long‐acting beta2‐agonists than either inhaler alone for the treatment of COPD?
Chronic obstructive pulmonary disease (COPD) is a lung disease which includes the conditions chronic bronchitis and emphysema. The symptoms include breathlessness and a chronic cough. COPD is an irreversible disease that is usually brought on by airway irritants, such as smoking or inhaled dust.
Long‐acting beta2‐agonists and tiotropium are two types of inhaled medications that help widen the airways (bronchodilators) for up to 12 to 24 hours. These bronchodilators are commonly used to manage persistent symptoms of COPD. They can be used in combination or on their own. These bronchodilators work in different ways and therefore might be more beneficial if used together. The purpose of this review was to determine the benefits and risks of using a combination of both types of bronchodilator compared to the individual bronchodilators.
We found five studies involving 3263 patients comparing the long‐term efficacy and side effects of combining tiotropium with a long‐acting beta2‐agonist. The combination of tiotropium plus long‐acting beta2‐agonist resulted, on average, in a slightly better quality of life and lung function for the patients compared to using only tiotropium, but did not show a difference in hospital admissions or mortality. There were not enough data to determine the risks and benefits of tiotropium plus long‐acting beta2‐agonist treatment compared to long‐acting beta2‐agonist alone.
