Meta-analysis finds inhaled corticosteroids associated with reduced cardiovascular mortality in COPD patients
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Key Takeaway
Consider observational association between ICS and reduced cardiovascular mortality in COPD when evaluating therapy.
This systematic review and meta-analysis examined the association between inhaled corticosteroid (ICS) use and cardiovascular mortality in 74,004 patients with COPD. The analysis compared various ICS-containing inhaled formulations (including ICS monotherapy, ICS/LABA combinations, and triple ICS/LAMA/LABA therapy) against multiple comparators: formulations without ICS, dual LAMA/LABA therapy, placebo, and LABA monotherapy.
The primary finding was a significant association between ICS use and reduced risk of cardiovascular deaths. Compared to formulations without ICS, ICS-containing regimens showed a risk ratio of 0.84 (95% CI 0.74-0.95). Triple therapy (ICS/LAMA/LABA) showed the strongest association versus dual LAMA/LABA therapy (RR 0.56, 95% CI 0.37-0.86). ICS monotherapy versus placebo was associated with reduced risk (RR 0.81, 95% CI 0.66-0.99), while ICS/LABA versus LABA monotherapy showed no significant difference (RR 0.98, 95% CI 0.80-1.20).
Safety and tolerability data were not reported. Key limitations include the observational nature of the findings, which indicate association rather than proven causation. The study design aggregates data from multiple trials, and details about follow-up duration, patient settings, and funding sources were not provided. For practice, these findings suggest a potential cardiovascular mortality benefit associated with ICS use in COPD, but treatment decisions should continue to prioritize established indications for ICS based on exacerbation history and symptom burden, recognizing these are observational associations.
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View Original Abstract ↓
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-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.
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