Tiotropium Respimat Inhaler and the Risk of Death in COPD
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Abstract
Background
Tiotropium delivered at a dose of 5 μg with the Respimat inhaler showed efficacy
similar to that of 18 μg of tiotropium delivered with the HandiHaler inhalation device
in placebo-controlled trials involving patients with chronic obstructive pulmonary
disease (COPD). Although tiotropium HandiHaler was associated with reduced mortality,
as compared with placebo, more deaths were reported with tiotropium Respimat
than with placebo.
Methods
In this randomized, double-blind, parallel-group trial involving 17,135 patients
with COPD, we evaluated the safety and efficacy of tiotropium Respimat at a oncedaily
dose of 2.5 μg or 5 μg, as compared with tiotropium HandiHaler at a oncedaily
dose of 18 μg. Primary end points were the risk of death (noninferiority study,
Respimat at a dose of 5 μg or 2.5 μg vs. HandiHaler) and the risk of the first
COPD exacerbation (superiority study, Respimat at a dose of 5 μg vs. HandiHaler).
We also assessed cardiovascular safety, including safety in patients with stable
cardiac disease.
Results
During a mean follow-up of 2.3 years, Respimat was noninferior to HandiHaler with
respect to the risk of death (Respimat at a dose of 5 μg vs. HandiHaler: hazard
ratio, 0.96; 95% confidence interval [CI], 0.84 to 1.09; Respimat at a dose of 2.5 μg
vs. HandiHaler: hazard ratio, 1.00; 95% CI, 0.87 to 1.14) and not superior to HandiHaler
with respect to the risk of the first exacerbation (Respimat at a dose of 5 μg
vs. HandiHaler: hazard ratio, 0.98; 95% CI, 0.93 to 1.03). Causes of death and incidences
of major cardiovascular adverse events were similar in the three groups.
Conclusions
Tiotropium Respimat at a dose of 5 μg or 2.5 μg had a safety profile and exacerbation
efficacy similar to those of tiotropium HandiHaler at a dose of 18 μg in patients
with COPD. (Funded by Boehringer Ingelheim; TIOSPIR ClinicalTrials.gov number,
NCT01126437.