Plain language summary
Combined inhalers versus placebo for the treatment of chronic obstructive pulmonary disease (COPD)
We reviewed the evidence on the effects of combined inhalers in people with COPD when compared with placebo. We particularly focused on whether combined inhalers are a good but safe treatment for adults with COPD.
COPD is a serious respiratory condition that affects millions of people worldwide. In most cases, it is caused by smoking. COPD is often treated by using inhalers. Currently, three types of inhalers combine a steroid and a 'long-acting beta2-agonist' (LABA). Steroids work by reducing inflammation in the airways, and LABA work by relaxing the muscles in the airways and opening them up. Using combined inhalers is more convenient than taking the two drugs separately but is also more expensive. We looked for evidence on whether giving a combined inhaler is better or worse than giving placebo (dummy inhaler).
Nineteen studies involving 10,400 people were included in this review. The studies lasted between 4 and 156 weeks. All of the people included in the studies had COPD of different severity. Both men and women were included, and most of the studies included only adults aged 45 or older.
All studies compared a combined inhaler with a placebo that was identical in appearance to the combined inhaler, so the people in the trials did not know whether they were taking the drug or the dummy inhaler. Some of the studies included two groups treated with the combined inhaler; one group was getting a higher dose and one group was getting a lower dose.
The evidence presented here is current to June 2013.
Most of the studies were sponsored by the pharmaceutical industry.
We found that people receiving a combined inhaler were less likely to have a flare-up (‘exacerbation’) of their COPD. The chance of having an exacerbation was reduced by about one quarter.
A small reduction in the risk of death was seen over three years, although most of the evidence about death comes from one large, long trial called TORCH. According to TORCH, approximately 42 people would need to be treated with a combined inhaler for three years to prevent one death.
We also found that people receiving combined inhalers had small improvements in quality of life, symptoms related to COPD and their breathing tests. However, these improvements may not have been very noticeable to them.
People treated with combined inhalers were more likely to have a lung infection called pneumonia. Again, most of the evidence about pneumonia comes from the TORCH trial. According to TORCH, when compared with placebo, for approximately every 17 people treated with combined inhaler, one extra person would get pneumonia.
People treated with combined inhalers were no more or less likely to experience serious unwanted events, including side effects, during treatment.
No consistent differences were found between the three different types of inhalers included in this review.
Quality of the evidence
The evidence presented in this review is generally considered to be of moderate quality. Most of the studies did not clearly explain how they decided which people would receive the combined inhaler and which would receive placebo, and this is an important part of a well-conducted study. Also, more people receiving placebo dropped out of the trials than those receiving a combined inhaler. This often happened because of exacerbations of COPD. This means that by the end of the trial, the groups might have been unbalanced, and this could affect the accuracy of the results.