Inhaled corticosteroid containing combinations and mortality in COPD

Abstract

There is no solid evidence that any pharmacological treatment reduces mortality in chronic obstructive pulmonary disease (COPD). Two large trials with mortality as an efficacy outcome have been carried out testing a combination of a long-acting beta-agonist (LABA) and an inhaled corticosteroid (ICS) and in both, the reduction in mortality failed to reach statistical significance [1,2]. This could be seen as proof of absence of effect, but given that the TORCH trial [1] resulted in a hazard ratio (HR) of 0.825 (95% CI 0.681-1.002; p=0.052) for the comparison of combined fluticasone propionate and salmeterol with placebo, the interpretation may not be that simple. The other negative trial, the SUMMIT trial [2], only included patients with moderate COPD and increased risk of cardiovascular comorbidity.

Reduction in All-Cause Mortality with Fluticasone Furoate/Umeclidinium/Vilanterol in Patients with Chronic Obstructive Pulmonary Disease

“…This finding was consistently observed in the on-treatment analyses, the analyses that included offtreatment data, and in sensitivity tipping point analyses. These data extend previous studies that suggested a reduction in mortality using ICS-containing medications in patients with COPD (5,6,8,13,14). We confirm a survival benefit to ICScontaining therapy in a predefined, prospective analysis.…”

“…The endpoint did not reach statistical significance in the study, although that may be because that study was powered assuming a 30% reduction in mortality in a much milder patient population. A post hoc, stratified, safety-pooled analysis of fatal adverse events of ICS-containing therapy in three 52-week studies suggested a 29% reduction in mortality, although this did not reach statistical significance (HR, 0.71 [95% CI, 0.50-1.02]; P = 0.066) (13). Interestingly, a recent Bayesian network meta-analysis of 219 trials found that both ICS/LAMA/LABA and ICS/LABA were associated with a statistically significantly higher probability of reducing mortality compared with placebo (odds ratio [OR], 0.74 [95% credible interval, 0.59 to 0.93]; posterior probability of OR .…”

Blood Eosinophil Counts, Withdrawal of Inhaled Corticosteroids and Risk of COPD Exacerbations and Mortality in the Clinical Practice Research Datalink (CPRD)

“…However, the INSPIRE trial which included severe and very severe COPD patients receiving LABA/ICS experienced fewer deaths than those receiving LAMA (32). Furthermore, Vestbo et al (33) performed a stratified pooled analysis of all fatal adverse events comparing ICS-containing versus ICS-free treatments in three recent 52-week studies among patients with severe to very severe COPD at increased risk for exacerbations. They found no statistically significant reduction in the risk of developing a fatal event.…”

Triple therapy for COPD: a crude analysis from a systematic review of the evidence

“…Of interest, a recent pooled analysis of the BDP/FOR/GB triple combination therapy showed this effect only for nonrespiratory cause of mortality. 42 Of note, there are a number of well-known factors that are associated with mortality in COPD patients. [43][44][45] Therefore, additional studies are needed to explore the impact of triple therapy on mortality as a primary outcome.…”