Inhaled corticosteroids in chronic obstructive pulmonary disease: a systematic review and meta-analysis on mortality protection - making a long story short

Introduction: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide, primarily due to persistent airflow limitation from tobacco and biomass smoke exposure. While inhaled corticosteroids (ICS) combined with long-acting bronchodilators, namely long-acting β2-adrenoreceptor agonists (LABA) and long-acting muscarinic antagonists (LAMA), are recommended for symptom control and exacerbation reduction, their effect on mortality remains uncertain. Recent randomized controlled trials (RCTs) suggest potential mortality benefits with triple ICS/LABA/LAMA therapy, though findings are not definitive. Methods: We conducted a systematic review and network meta-analysis (NMA) to evaluate the impact of ICS-containing therapies on all-cause mortality in COPD. Searches were performed across ClinicalTrials.gov, Cochrane Library, EMBASE, MEDLINE, and SCOPUS, focusing on RCTs measuring mortality as an efficacy outcome. Results: A total of 42,784 COPD patients from five high-quality studies were included. Pairwise meta-analysis showed a significant reduction in all-cause mortality with ICS-containing therapies (RR 0.80, 95% CI 0.68–0.95), particularly with ICS/LABA and ICS/LABA/LAMA combinations. The NMA ranked ICS/LABA/LAMA as the most effective treatment (SUCRA 0.89). Conclusions: This study provides compelling evidence that ICS-containing therapies, particularly triple therapy, significantly reduce all-cause mortality in COPD patients. Future research should identify patient subgroups most likely to benefit while minimizing adverse effects. Registration: PROSPERO registration ID: CRD42024607568.