LAMA-LABA-ICS Triple Therapy Provides Mortality Benefit Over LAMA-LABA Dual Therapy in This Patient
For this 59-year-old woman with severe COPD and eosinophils of 0.29 (290 cells/μL), LAMA-LABA-ICS triple therapy is strongly recommended over LAMA-LABA dual therapy because it reduces mortality and prevents exacerbations. 1
Mortality Benefit
The most recent and highest quality evidence demonstrates a clear mortality advantage with triple therapy:
The 2023 Canadian Thoracic Society guidelines provide a strong recommendation for LAMA/LABA/ICS triple therapy over LAMA/LABA dual therapy specifically for mortality reduction in patients at high risk of exacerbations with moderate-to-high symptom burden and impaired lung function (FEV₁ < 80% predicted). 1
This recommendation is based on moderate certainty evidence showing greater reduction in mortality with triple therapy compared to dual bronchodilator therapy. 1
The ETHOS study specifically demonstrated a mortality benefit favoring moderate-dose inhaled corticosteroid triple combination therapy. 1
Morbidity Benefits (Exacerbation Reduction)
Triple therapy provides substantial morbidity benefits beyond mortality:
Moderate certainty evidence shows greater reduction in exacerbation rates with LAMA/LABA/ICS compared to LAMA/LABA dual therapy. 1
The number needed to treat is 4 patients for 1 year to prevent one moderate-to-severe exacerbation with triple therapy versus dual bronchodilator therapy. 1
Triple therapy improves lung function, health status, and dyspnea as secondary outcomes. 1
Eosinophil Count Consideration
This patient's eosinophil count of 0.29 (290 cells/μL) supports ICS use:
Blood eosinophil counts predict ICS treatment effects on exacerbation prevention, with higher counts indicating greater benefit. 1
While the 2017 GOLD guidelines note that eosinophil counts ≥300 cells/μL particularly predict ICS benefit, this patient's count of 290 cells/μL is at the threshold. 1
Withdrawing ICS is particularly harmful in patients with blood eosinophil counts ≥300 cells/μL, suggesting benefit at this level. 1
Post-hoc analyses show that higher blood eosinophil counts predict increased exacerbation rates in patients treated with LABAs without ICS, and greater treatment effect of ICS/LABA versus LABA on exacerbations. 1
Risk-Benefit Profile
The pneumonia risk with ICS must be balanced against mortality and exacerbation benefits:
The number needed to harm is 33 patients for 1 year to cause one pneumonia event, while the number needed to treat is only 4 to prevent one exacerbation. 1
This favorable 8:1 benefit-to-harm ratio strongly supports triple therapy in this high-risk patient. 1
Pneumonia risk is a class effect of ICS-containing therapies, with no conclusive evidence of intra-class differences. 1
Clinical Algorithm for This Patient
Given severe COPD (by definition FEV₁ < 50% predicted), this patient meets criteria for high exacerbation risk if she has:
≥2 moderate exacerbations OR ≥1 severe exacerbation (requiring hospitalization/ED visit) in the past year → Use LAMA/LABA/ICS triple therapy 1
If she also has moderate-to-high symptom burden (CAT ≥10 or mMRC ≥2), this further strengthens the indication for triple therapy 1
Important Caveats
Do not step down from triple therapy to dual therapy once initiated, as withdrawing ICS can lower health status, lung function, and increase exacerbation risk, especially with eosinophils near 300 cells/μL. 1
Single-inhaler triple therapy is preferred over multiple-inhaler regimens for better adherence and demonstrated incremental benefit. 1
Moderate-dose ICS (not high-dose) provides optimal benefit with the mortality advantage, as higher doses increase adverse effects without additional exacerbation reduction. 1