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Re-evaluation of combination therapy in chronic obstructive pulmonary disease (COPD).
- Source :
-
Respiratory medicine [Respir Med] 2019 May; Vol. 151, pp. 27-34. Date of Electronic Publication: 2019 Mar 29. - Publication Year :
- 2019
-
Abstract
- Background: Clinical trials of COPD pharmacotherapy typically involve aging populations with moderate-to-severe COPD, but the latter is often diagnosed by spirometric criteria that are not age-appropriate across the continuum of lung function. We have therefore re-evaluated the clinical effect of combination therapy (salmeterol plus fluticasone) in moderate-to-severe COPD, using more age-appropriate spirometric criteria from the Global Lung Function Initiative (GLI) and trial data from Towards a Revolution in COPD Health (TORCH).<br />Methods: Of the 6112 TORCH participants, 5688 (93.1%) had GLI-based moderate-to-severe COPD (mean age 64.8 years). The primary outcome was all-cause mortality and the primary comparison was combination therapy vs. placebo. Secondary outcomes included COPD and cardiovascular (CV) mortality and pneumonia. A modified intention-to-treat analysis evaluated differences in time-to-event over a three-year period, using Cox proportional hazards models with statistical significance at p < 0.010 (acknowledging repeated significance testing).<br />Results: Relative to placebo, combination therapy yielded a statistically non-significant reduction in all-cause mortality-adjusted hazard ratio [adjHR] 0.78 (95% confidence interval [CI]: 0.64, 0.95), p = 0.012. Relative to placebo, combination therapy also yielded statistically non-significant reductions in COPD and CV mortality-adjHR 0.75 (95% CI: 0.55, 1.02), p = 0.068 and adjHR 0.76 (95% CI: 0.53, 1.09), p = 0.135, respectively. In contrast, combination therapy yielded a statistically significant increased risk of pneumonia, relative to placebo-adjHR 1.80 (95% CI: 1.46, 2.21), p < 0.001.<br />Conclusion: In GLI-based moderate-to-severe COPD, combination therapy yields a statistically significant increased risk of pneumonia but the reductions in mortality are not statistically significant, although could potentially be clinically meaningful.<br /> (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Subjects :
- Aged
Cardiovascular Diseases mortality
Female
Fluticasone therapeutic use
Humans
Male
Middle Aged
Multicenter Studies as Topic
Pneumonia epidemiology
Proportional Hazards Models
Randomized Controlled Trials as Topic
Salmeterol Xinafoate therapeutic use
Severity of Illness Index
Spirometry
Bronchodilator Agents therapeutic use
Fluticasone-Salmeterol Drug Combination therapeutic use
Pulmonary Disease, Chronic Obstructive drug therapy
Pulmonary Disease, Chronic Obstructive mortality
Subjects
Details
- Language :
- English
- ISSN :
- 1532-3064
- Volume :
- 151
- Database :
- MEDLINE
- Journal :
- Respiratory medicine
- Publication Type :
- Academic Journal
- Accession number :
- 31047114
- Full Text :
- https://doi.org/10.1016/j.rmed.2019.03.020