A meta-analysis of 60 randomized controlled trials examines all-cause mortality In 103,034 patients with COPD who were using inhaled therapy with or without inhaled corticosteroids (ICSs). Mortality was reduced by 10% with inhaled therapy containing ICSs and by 27% when triple therapy was used for longer than 6 months. The greatest reduction in mortality was associated with patient eosinophil counts of 200 or more per microliter, with a 42% reduction in the Peto odds ratio.
Editorial: “Although the results of this study were positive, [these findings] should be interpreted with thoughtfulness, because the analysis was affected by substantial heterogeneity resulting not only from the inclusion of several studies that enrolled heterogeneous populations of COPD patients, but also because several formulations characterized by different regimens of administrations (once daily vs twice daily) were compared and administered via different inhaler devices,” editorialists write. “Moreover, several formulations were compared, although there was not consistency between the bronchodilators included in each combination. Examples of these problematic conditions could be the comparison between beclomethasone/formoterol/glycopyrronium combination (twice daily) and tiotropium (once daily, LAMA different than in the triple [fixed-dose comparison (FDCs)]), or the comparison between salmeterol/fluticasone combination and indacaterol/glycopyrronium combination (both LABA and LAMA different in the dual FDCs). Another limitation was related to the fact that no subset analyses for cardiovascular mortality was performed. Overall, these matters and the large number of included trials may lead to potential type I error in this pairwise meta-analysis.”