Association of Inhaled Corticosteroids With All-Cause Mortality Risk in Patients With COPD: A Meta-analysis of 60 Randomized Controlled Trials

Abstract

Inhaled corticosteroids (ICSs) have been used widely in the maintenance therapy of COPD. However, whether inhaled therapy containing ICSs can reduce the all-cause mortality risk and the possible benefited patient subgroups is unclear. Does inhaled therapy containing ICSs reduce the all-cause mortality risk in patients with COPD compared with other inhaled therapies not containing ICSs? We searched PubMed, Cochrane Library, Embase, and ClinicalTrials.gov for relevant randomized clinical trials (RCTs). Pooled results were calculated using Peto ORs with corresponding 95%CIs. Sixty RCTs enrolling 103,034 patients were analyzed. Inhaled therapy containing ICSs (Peto OR, 0.90; 95%CI, 0.84-0.97), especially triple therapy (Peto OR, 0.73; 95%CI, 0.59-0.91), was associated with a reduction in the all-cause mortality risk among patients with COPD when compared with inhaled therapy without ICSs. Subgroup analyses revealed that treatment duration of > 6months (Peto OR, 0.90; 95%CI, 0.83-0.97), medium-dose ICSs (Peto OR, 0.71; 95%CI, 0.56-0.91), low-dose ICSs (Peto OR, 0.88; 95%CI, 0.79-0.97), and budesonide (Peto OR, 0.75; 95%CI, 0.59-0.94) were involved in this association. The predictors of this association included eosinophil counts of≥ 200/μL or percentage of≥ 2%, documented history of≥ 2 moderate and severe exacerbations in the previous year, Global Initiative for Chronic Obstructive Lung Disease stages III or IV, age younger than 65 years, and BMI of≥ 25kg/m2, among which eosinophil counts of≥ 200/μL (Peto OR, 0.58; 95%CI, 0.36-0.95) were the strongest predictor. Inhaled therapy containing ICSs, especially triple therapy, of longer than 6months was associated with a reduction in the all-cause mortality risk in patients with COPD. The predictors of this association included medication factors and patient characteristics, among which eosinophil counts of≥ 200/μL were the strongest predictor. PROSPERO; No.: CRD42022304725; URL: https://www.crd.york.ac.uk/prospero/.