Comparative safety of inhaled medications in patients with chronic obstructive pulmonary disease: systematic review and mixed treatment comparison meta-analysis of randomised controlled trials.

Thorax 2013 Jan 6;68(1):48-56. Epub 2012 Oct 6.

Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.

Background: The active-treatment comparative safety information for all inhaled medications in patients with chronic obstructive pulmonary disease (COPD) is limited. We aimed to compare the risk of overall and cardiovascular death for inhaled medications in patients with COPD.

Methods: Through systematic database searching, we identified randomised controlled trials of tiotropium Soft Mist Inhaler, tiotropium HandiHaler, long-acting β2 agonists (LABAs), inhaled corticosteroids (ICS), and LABA-ICS combination with at least a 6-month treatment duration. Direct comparison and mixed treatment comparison (MTC) meta-analyses were conducted to estimate the pooled ORs of death for each comparison.

Results: 42 trials with 52 516 subjects were included. The MTC meta-analysis with the fixed effect model indicated tiotropium Soft Mist Inhaler was associated with an universally increased risk of overall death compared with placebo (OR 1.51; 95% CI 1.06 to 2.19), tiotropium HandiHaler (OR 1.65; 95% CI 1.13 to 2.43), LABA (OR 1.63; 95% CI 1.10 to 2.44) and LABA-ICS (OR 1.90; 95% CI 1.28 to 2.86). The risk was more evident for cardiovascular death, in patients with severe COPD, and at a higher daily dose. LABA-ICS was associated with the lowest risk of death among all treatments. No excess risk was noted for tiotropium HandiHaler or LABA. The results were similar for MTC and direct comparison meta-analyses, with less precision in the random effects model.

Conclusion: Our study provided a comparative safety spectrum for each category of inhaled medications. Tiotropium Soft Mist Inhaler had a higher risk of mortality and should be used with caution.

Download full-text PDF

Source
http://dx.doi.org/10.1136/thoraxjnl-2012-201926DOI Listing
January 2013
46 Reads

Publication Analysis

Top Keywords

inhaled medications
16
medications patients
12
soft mist
12
tiotropium soft
12
tiotropium handihaler
12
mist inhaler
12
comparative safety
12
randomised controlled
8
safety inhaled
8
mixed treatment
8
treatment comparison
8
risk death
8
direct comparison
8
pulmonary disease
8
chronic obstructive
8
controlled trials
8
obstructive pulmonary
8
cardiovascular death
8
patients chronic
8
tiotropium
6

Similar Publications