What are the recommended drug combinations (LABA (long‑acting β2‑agonist) + LAMA (long‑acting muscarinic antagonist), LABA + ICS (inhaled corticosteroid), and triple therapy) for adult patients with stable chronic obstructive pulmonary disease (COPD) in India?

COPD Drug Combinations in India

For adult patients with stable COPD in India, the recommended drug combinations follow a risk-stratified approach: LABA + LAMA dual therapy is the preferred initial treatment for high-risk patients (Group D), while LABA + ICS should be reserved for specific phenotypes (asthma-COPD overlap or high eosinophils), and triple therapy (LABA + LAMA + ICS) is indicated for patients with persistent exacerbations despite dual bronchodilator therapy. 1

Initial Treatment Selection by COPD Severity

For Low Symptom, Low Risk Patients (Group A)

• Start with short-acting bronchodilators (SABA or SAMA) as needed 2
• Long-acting bronchodilators are not required initially for this group 1

For High Symptom, Low Risk Patients (Group B)

• Initiate with a single long-acting bronchodilator (LABA or LAMA) - no evidence favors one class over another 1, 2
• For persistent breathlessness on monotherapy, escalate to LABA + LAMA dual therapy 1
• Patients with severe breathlessness may start directly on dual bronchodilators 1

For High Symptom, High Risk Patients (Group D)

• LABA + LAMA combination is the preferred initial therapy for three critical reasons 1:
  • Superior patient-reported outcomes compared to single bronchodilators 1
  • Better exacerbation prevention than LABA + ICS combinations 1
  • Lower pneumonia risk compared to ICS-containing regimens 1

When to Use LABA + ICS Instead of LABA + LAMA

LABA + ICS may be the first-choice initial therapy in specific patient subgroups 1:

• Patients with history or findings suggestive of asthma-COPD overlap (ACO) 1, 2
• Patients with high blood eosinophil counts (≥300 cells/μL) 3

However, LABA + ICS is less effective than LABA + LAMA for preventing exacerbations in typical COPD patients 1. The combination reduces exacerbations compared to LABA alone but does not significantly reduce hospitalizations and carries a 4% increased pneumonia risk 1.

Escalation to Triple Therapy (LABA + LAMA + ICS)

Triple therapy should be considered for patients who develop additional exacerbations on LABA + LAMA therapy 1, 2. The evidence supporting this escalation includes:

• Triple therapy improves lung function, symptoms, and health status compared to ICS/LABA or LAMA monotherapy 1, 3
• Reduces exacerbation risk more effectively than dual therapies 1, 3, 4
• Fixed-dose triple combinations (fluticasone furoate/umeclidinium/vilanterol or beclometasone/formoterol/glycopyrronium) show superior outcomes 5, 4

Alternative Pathway for Exacerbations

If patients develop exacerbations on LABA + LAMA, an alternative is to switch to LABA + ICS first 1. If this doesn't control exacerbations/symptoms, then add LAMA to create triple therapy 1.

Critical Safety Considerations

Pneumonia Risk with ICS

• ICS use significantly increases pneumonia risk, especially in severe disease 1
• High-risk patients include: current smokers, age ≥55 years, prior exacerbations/pneumonia, BMI <25 kg/m², severe airflow limitation 1, 3
• The benefit-risk ratio shows number needed to treat of 4 to prevent one exacerbation versus number needed to harm of 33 for pneumonia 3

Other ICS-Related Adverse Effects

• Oral candidiasis, hoarse voice, skin bruising 1
• Potential increased risk of diabetes, cataracts, mycobacterial infections including tuberculosis 1
• Variable results regarding bone density and fractures 1

Additional Therapies for Persistent Exacerbations

If patients on triple therapy continue to exacerbate, consider 1, 2:

• Roflumilast: For FEV1 <50% predicted with chronic bronchitis phenotype, particularly if hospitalized for exacerbation in previous year 1, 2
• Macrolide therapy (azithromycin or erythromycin): In former smokers only, with awareness of bacterial resistance risk and hearing impairment 1

Key Clinical Pitfalls to Avoid

• Never use ICS as monotherapy in COPD - it must be combined with bronchodilators 2
• Avoid long-term oral corticosteroids - no benefits with numerous side effects 1
• Don't combine short-acting and long-acting agents of the same class unnecessarily - this increases side effects without clear benefit 1
• Consider ICS withdrawal in patients on triple therapy without clear benefit, as stopping ICS shows no significant harm 1

Practical Implementation

LABA + LAMA combinations are superior to LABA + ICS combinations for typical COPD patients because 1:

• Greater reduction in exacerbations 1
• Improved FEV1 and symptom control 1
• Reduced hospitalizations 1
• Lower pneumonia risk 1

Single-inhaler triple therapy may improve adherence compared to multiple inhalers 3, making fixed-dose combinations (beclometasone/formoterol/glycopyrronium or fluticasone furoate/vilanterol/umeclidinium) preferable when triple therapy is indicated 5, 4.