Comparative safety of inhaled medications in patients with chronic obstructive pulmonary disease: systematic review and mixed treatment comparison meta-analysis of randomised controlled trials
Resource
Thorax, 68(1), 48-56
Journal
Thorax
Journal Volume
68
Journal Issue
1
Pages
48-56
Date Issued
2013
Date
2013
Author(s)
Abstract
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 beta 2 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.
SDGs
Other Subjects
beta 2 adrenergic receptor stimulating agent; corticosteroid; long acting drug; placebo; tiotropium bromide; adult; aged; article; cause of death; chronic obstructive lung disease; clinical effectiveness; controlled study; disease association; disease severity; drug effect; drug efficacy; drug fatality; drug safety; female; heart death; human; major clinical study; male; meta analysis; priority journal; randomized controlled trial (topic); risk assessment; survival rate; systematic review; treatment duration
Type
journal article
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