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

IntroductionChronic 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 beta 2-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.MethodsWe 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.ResultsA 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).ConclusionsThis 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.RegistrationPROSPERO registration ID: CRD42024607568