All-Cause and Cardiovascular Mortality With Single Inhaler Triple Therapy Versus Double Therapies for COPD: A Systematic Review and Metanalysis.
Summary
In a meta-analysis of 11 RCTs (n=25,774), single-inhaler triple therapy (ICS/LABA/LAMA) significantly reduced all-cause mortality (HR 0.727) and cardiovascular mortality (HR 0.455) versus LABA/LAMA, without affecting MACEs. No significant differences were observed versus LABA/ICS for mortality or MACEs.
Key Findings
- SITT reduced all-cause mortality vs LABA/LAMA: pooled HR 0.727 (95% CI 0.574–0.921).
- SITT reduced cardiovascular mortality vs LABA/LAMA: pooled HR 0.455 (95% CI 0.292–0.710).
- No significant differences between SITT and LABA/ICS in ACM, cardiovascular mortality, or MACEs.
Clinical Implications
For COPD patients at high risk, SITT should be prioritized over LABA/LAMA when mortality reduction is a goal; clinicians should weigh benefits against individual ICS-related risks while noting no excess MACEs.
Why It Matters
This provides the strongest to-date randomized evidence that triple therapy confers a mortality advantage over LABA/LAMA, a key comparator in COPD management, with direct implications for guidelines and payer policies.
Limitations
- Potential heterogeneity across trials and lack of individual patient data for subgroup analyses
- MACEs were not reduced, and safety signals (e.g., ICS-related pneumonia) were not detailed here
Future Directions
IPD meta-analyses to identify phenotypes driving mortality benefit, and pragmatic trials comparing SITT sequencing and de-escalation strategies with safety profiling.
Study Information
- Study Type
- Meta-analysis
- Research Domain
- Treatment
- Evidence Level
- I - Meta-analysis of randomized controlled trials with mortality endpoints
- Study Design
- OTHER