The findings add weight to recent safety concerns by regulatory agencies regarding the possibility of an increased mortality risk associated with this device.
COPD is an umbrella term for chronic lung diseases, such as emphysema and bronchitis, which block the airways and restrict oxygen flow around the body. It is currently ranked the fourth leading cause of death worldwide.
Inhaled tiotropium is available in two formulations: as a powder, delivered with a Handihaler device, and as a mist, delivered with the Respimat Soft Mist Inhaler. Both devices are manufactured by Boehringer Ingelheim.
The mist inhaler is available in 55 countries, including England and Scotland, but has yet to gain regulatory approval in the United States.
So a team of UK and US researchers analysed data from randomised controlled trials to compare the risk of mortality associated with inhaled tiotropium delivered by the mist inhaler with placebo in patients with COPD.
Differences in study design and quality were taken into account to minimise bias.
Five trials involving 6,522 participants met the criteria for analysis. The researchers found that tiotropium delivered with the Respimat Soft Mist Inhaler (5 μg dose) was associated with a 52% increased risk of mortality in patients with COPD compared with placebo.
This means that one excess death would be expected for every 124 patients treated with 5 μg of tiotropium delivered by mist inhaler for one year compared with placebo.
The authors conclude that their analysis explains safety concerns by regulatory agencies regarding the possibility of an increased risk of mortality associated with tiotropium mist inhaler in patients with chronic obstructive pulmonary disease.
In accordance with guidance from the Medicines and Healthcare Products Regulatory Agency, they say clinicians should inform patients about the possibility of this increased risk and exercise caution when prescribing tiotropium mist inhaler, particularly in patients with possible underlying cardiac disease.
This view is reiterated in an accompanying editorial by Christopher Cates from St George's University of London who says, pending the results of a head to head trial, indirect evidence suggests that the Handihaler is a safer bet than the Respimat.
He adds, if patients have a strong preference for the mist inhaler, the possible increased risk in mortality will need to be shared with them.
Source
British Medical Journal