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Respir Med. 2019 May;151:27-34. doi: 10.1016/j.rmed.2019.03.020. Epub 2019 Mar 29.

Re-evaluation of combination therapy in chronic obstructive pulmonary disease (COPD).

Author information

1
Veterans Affairs (VA) Connecticut Healthcare System, West Haven, CT, USA; Yale University School of Medicine, Department of Internal Medicine, New Haven, CT, USA. Electronic address: carlos.fragoso@yale.edu.
2
Yale University School of Medicine, Department of Internal Medicine, New Haven, CT, USA.

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).

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).

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.

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.

KEYWORDS:

COPD; Mortality; Pharmacotherapy; Pneumonia; Spirometry

PMID:
31047114
PMCID:
PMC6519718
[Available on 2020-05-01]
DOI:
10.1016/j.rmed.2019.03.020

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