Can a COPD Patient Be on Trilogy and a LAMA Simultaneously?
No, a patient should not be on both Trilogy (which contains a LAMA) and a separate LAMA simultaneously, as this would result in therapeutic duplication and increased risk of anticholinergic side effects without additional benefit.
Understanding Trilogy Composition
Trilogy is a single-inhaler triple therapy device that already contains:
- Budesonide (inhaled corticosteroid/ICS)
- Glycopyrrolate (long-acting muscarinic antagonist/LAMA)
- Formoterol (long-acting β2-agonist/LABA)
Since Trilogy already includes glycopyrrolate as the LAMA component, adding another LAMA (such as tiotropium, umeclidinium, or aclidinium) would constitute double LAMA therapy, which is not supported by evidence and poses unnecessary risks 1, 2.
Evidence for Triple Therapy Approach
The 2023 Canadian Thoracic Society guidelines strongly recommend LAMA/LABA/ICS triple combination therapy over LABA/LAMA dual therapy for patients with:
- High risk of exacerbations (≥2 moderate or ≥1 severe exacerbation in the past year)
- Moderate to high symptom burden (CAT ≥10, mMRC ≥2)
- Impaired lung function (FEV1 <80% predicted)
This recommendation is based on moderate certainty evidence showing greater reduction in mortality, prevention of moderate-severe exacerbations, and improvements in dyspnea, health status, and lung function 1.
Clinical Rationale Against Dual LAMA Therapy
There is no evidence supporting the use of two LAMAs concurrently. The guideline-recommended approach uses a single LAMA as part of combination therapy:
- LAMA monotherapy for patients with lower symptom burden 1
- LAMA/LABA dual therapy for symptomatic patients 3
- LAMA/LABA/ICS triple therapy for high-risk patients with exacerbations 1, 2
Triple therapy improves lung function, symptoms, and health status compared to ICS/LABA or LAMA monotherapy, and reduces exacerbations 1. The ETHOS study demonstrated a mortality benefit with triple therapy at moderate ICS doses 2.
Safety Considerations
Adding a second LAMA would increase anticholinergic burden without proven benefit, potentially causing:
- Dry mouth
- Urinary retention
- Constipation
- Blurred vision
- Increased cardiovascular events
The number needed to treat with triple therapy to prevent one moderate-to-severe exacerbation is 4, versus a number needed to harm of 33 for pneumonia, demonstrating a favorable benefit-risk ratio when used appropriately 2.
Correct Therapeutic Approach
If a patient is already on Trilogy, this provides complete triple therapy coverage. No additional LAMA should be added 1, 2.
For patients requiring optimization:
- Ensure proper inhaler technique and adherence (Morisky Medication Adherence Scale assessment) 4
- Consider adding prophylactic macrolide therapy (azithromycin 250 mg daily or 500 mg three times weekly) for former smokers ≥65 years with frequent exacerbations despite triple therapy 1, 5
- Consider roflumilast (PDE4 inhibitor) for patients with chronic bronchitis, severe-to-very severe COPD, and history of exacerbations 1
- Evaluate for pulmonary rehabilitation within 3 weeks of any exacerbation 5
Common Pitfall to Avoid
The most critical error is assuming that "more is better" with bronchodilators. Single-inhaler triple therapy like Trilogy already provides maximal bronchodilation through the LAMA component. Adding another LAMA creates medication duplication without addressing the underlying pathophysiology more effectively 1, 2.