Carlos A Vaz Fragoso1, Thomas M Gill2, Linda S Leo-Summers2, Peter H Van Ness2. 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.
RCT Entities:
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.
Authors: Sanja Stanojevic; Angie Wade; Janet Stocks; John Hankinson; Allan L Coates; Huiqi Pan; Mark Rosenthal; Mary Corey; Patrick Lebecque; Tim J Cole Journal: Am J Respir Crit Care Med Date: 2007-11-15 Impact factor: 21.405
Authors: Jørgen Vestbo; Suzanne S Hurd; Alvar G Agustí; Paul W Jones; Claus Vogelmeier; Antonio Anzueto; Peter J Barnes; Leonardo M Fabbri; Fernando J Martinez; Masaharu Nishimura; Robert A Stockley; Don D Sin; Roberto Rodriguez-Roisin Journal: Am J Respir Crit Care Med Date: 2012-08-09 Impact factor: 21.405
Authors: Andrea Gershon; Ruth Croxford; Andrew Calzavara; Teresa To; Matthew B Stanbrook; Ross Upshur; Thérèse A Stukel Journal: JAMA Intern Med Date: 2013-07-08 Impact factor: 21.873
Authors: Carlos A Vaz Fragoso; Thomas M Gill; Gail McAvay; Philip H Quanjer; Peter H Van Ness; John Concato Journal: Am J Med Date: 2012-11-20 Impact factor: 4.965