Association between inhaled corticosteroids and risk of cardiovascular mortality in patients with COPD: a systematic review and meta-analysis

Background COPD frequently coexists with cardiovascular diseases. Cardiovascular death is also a major contributor to mortality in COPD patients. Inhaled corticosteroids (ICS), as the most commonly prescribed inhaled anti-inflammatory medications, have been widely used for management of COPD patients who experience frequent exacerbations. However, whether ICS have a cardiovascular protective effect remains unclear. The purpose of this work was to comprehensively ascertain the risks of cardiovascular deaths related to ICS in COPD patients. Methods PubMed, the Cochrane Library and Embase were searched to screen qualifying articles from September to November 2022. An updated search was conducted in October 2025. We identified trials of any ICS for treatment of COPD and reported on cardiovascular deaths. Meta-analyses were conducted to calculate risk ratios with 95% confidence intervals. The primary end-point was cardiovascular mortality. Findings 35 randomised controlled trials enrolling 74 004 subjects were analysed. Inhaled formulations containing ICS significantly reduced the risk of cardiovascular deaths compared with inhaled formulations without ICS (risk ratio 0.84, 95% CI 0.74–0.95). ICS/long-acting muscarinic antagonist (LAMA)/long-acting β 2 -agonist (LABA) significantly reduced the risk of cardiovascular deaths compared with dual LAMA/LABA therapy (risk ratio 0.56, 95% CI 0.37–0.86). ICS monotherapy also significantly reduced the risk of cardiovascular deaths compared with placebo (risk ratio 0.81, 95% CI 0.66–0.99). However, ICS/LABA did not significantly reduce the risk of cardiovascular deaths compared to LABA monotherapy (risk ratio 0.98, 95% CI 0.80–1.20). Conclusions Inhaled formulations containing ICS are associated with a reduced risk of cardiovascular deaths in patients with COPD.