COPD: which is the best therapy to cut exacerbations and mortality?

Takeaway

• In patients with stable chronic obstructive pulmonary disease (COPD), triple therapy with long-acting muscarinic antagonist (LAMA)/long-acting beta-agonists (LABA)/inhaled corticosteroids (ICS) was the most effective treatment in reducing total exacerbation and all-cause mortality compared with other regular inhaled therapies.

Why this matters

• There is no proper evidence regarding the best inhaled therapy in reducing total exacerbation and all-cause mortality in stable COPD.

Study design

• 219 trials involving 228,710 patients met eligibility criteria after a search across Medline, EMBASE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and other electronic databases.
• Funding: None.

Key results

• In triple combination therapy, LAMA/LABA/ICS vs other drugs and placebo had significantly higher probability of reducing:
  • total exacerbation risk (OR, 0.57; 95% credible interval [CrI], 0.5-0.64; posterior probability of OR>1 [P[OR>1]]<.001) and
  • moderate to severe exacerbations (OR, 0.56; 95% CrI, 0.47-0.68; P[OR>1]<.001).
• In dual combination therapy, ICS/LABA and LAMA/LABA had a higher probability of reducing:
  • total exacerbations (OR, 0.74; 95% CrI, 0.68-0.81; P[OR>1] <.001; vs OR, 0.7; 95% CrI, 0.65-0.76; P[OR>1]<.001, respectively) and
  • moderate to severe exacerbations (OR, 0.71; 95% CrI, 0.61-0.82; P[OR>1]<.001; vs OR, 0.69; 95% CrI, 0.6-0.79; P[OR >1]<.001, respectively).
• In single-drug therapy, LAMA vs LABA had a higher probability of reducing:
  • total exacerbation (OR, 0.77; 95% CrI, 0.73-0.81; P[OR>1]<.001 vs OR, 0.86; 95% CrI, 0.81-0.9; P[OR>1]<.001, respectively) and
  • moderate to severe exacerbations (OR, 0.73; 95% CrI, 0.66-0.81; P[OR>1]<.001 vs OR, 0.85; 95% CrI, 0.76-0.95; P[OR>1]<.001, respectively).
• ICS/LAMA/LABA and ICS/LABA vs placebo significantly reduced mortality (OR, 0.74; 95% CrI, 0.59-0.93; P=.004; and OR, 0.86; 95% CrI, 0.76-0.98; P=.015, respectively).
• ICS/LAMA/LABA inclined towards lower the risk for cardiovascular mortality but did not show significant results.
• ICS/LAMA/LABA increased the risk for pneumonia (OR, 1.58; 95% CrI, 1.26-2; P=1.00).

Limitations

• Fewer randomised trials were included.