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In people with stable COPD, using LABA and LAMA drugs together rather than alone improves quality of life and reduces breathlessness

Oba Y, Sarva ST, Dias S Efficacy and safety of long-acting beta-agonist/long-acting muscarinic antagonist combinations in COPD: a network meta-analysis. Thorax. 2016;71:15-25.

Review question

In people with chronic obstructive pulmonary disease (COPD), does a combination of long-acting β-agonist (LABA) and long-acting muscarinic antagonist (LAMA) drugs reduce symptoms and improve quality of life?

Background

COPD is a lung disease with inflammation. It reduces the flow of air through the lungs and is often associated with smoking. Symptoms of COPD include difficulty breathing, cough, wheezing, and chest tightness.

COPD can be treated, and several types of drugs can help control symptoms. Bronchodilator drugs, including LABAs and LAMAs, help relax muscles around the airways and make it easier to breath. Using a LABA and a LAMA together may control symptoms better than using either drug alone.

How the review was done

The researchers did a systematic review, searching for studies up to May 2015.

The found 23 randomized controlled trials with 27,172 people (average age 61 to 69 years, 52% to 96% men, 26% to 63% current smokers).

The key features of the trials were:

  • people had moderate or severe COPD, without a recent exacerbation;
  • people with asthma, other diseases that affect breathing, or cardiovascular disease were excluded;
  • treatment was a LABA drug (formoterol, indacaterol, olodaterol, salmeterol, or vilanterol) combined with a LAMA drug (aclidinium, glycopyrronium, umeclidinium, or tiotropium);
  • combination treatment was compared with placebo or a LABA or LAMA drug alone;
  • people were treated for 12 weeks or more; and
  • most people did not know which treatment they were getting during the trials.

Trials were combined using a type of analysis (“network meta-analysis”) that lets you compare treatments even if they were not compared directly in the individual trials.

What the researchers found

Compared with placebo, LABA/LAMA combination:

  • improved quality of life and breathlessness when measured at 3 and 6 months;
  • reduced moderate-to-severe exacerbations; and
  • had similar rates of severe exacerbations, death, and serious adverse events.

Compared with LABA alone, LABA/LAMA combination:

  • improved quality of life when measured at 3 months and breathlessness when measured at 3 and 6 months;
  • reduced moderate-to-severe exacerbations; and
  • had similar quality of life when measured at 6 months and similar rates of severe exacerbations, death, and serious adverse events.

Compared with LAMA alone, LABA/LAMA combination:

  • improved quality of life and breathlessness when measured at 3 and 6 months; and
  • had similar rates of moderate-to-severe exacerbations, severe exacerbations, death, and serious adverse events.

Conclusions

In people with stable COPD, a LABA/LAMA combination improves quality of life and reduces breathlessness more than placebo, a LABA alone, or a LAMA alone. Treatments had similar rates of adverse events, including deaths.

LABA/LAMA drug combination vs placebo, LABA alone, or LAMA alone in COPD

Outcomes

Number of trials (people)

Effect of combination treatment*

Quality of life at 6 months

12 trials (18,536 people)

More people had improved quality of life than with placebo or LABA or LAMA alone

Breathlessness at 6 months

7 trials (9,045 people)

More people had improved breathlessness than with placebo or LABA or LAMA alone

Moderate-to-severe exacerbations

16 trials (18,224 people)

Fewer people had moderate or severe exacerbations than with placebo or LABA alone

 

 

No difference in effect between LABA/LAMA and LAMA alone

Severe exacerbations

19 trials (25,401 people)

No difference in effect between LABA/LAMA and placebo or LABA or LAMA alone

Death

15 trials (24,041 people)

No difference in effect between LABA/LAMA and placebo or LABA or LAMA alone

Serious adverse events

20 trials (27,172 people)

No difference in effect between LABA/LAMA and placebo or LABA or LAMA alone

COPD = chronic obstructive pulmonary disease; LABA = long-acting β-agonist; LAMA = long-acting muscarinic antagonist.

*Trials were combined using a type of analysis that lets you compare treatments even if they were not compared directly in the individual trials.



Related Topics


Glossary

Meta-analysis
Advanced statistical methods contrasting and combining results from different studies.
Network meta-analysis
An approach that simultaneously compares multiple treatments.
Placebo
A harmless, inactive, and simulated treatment.
Randomized controlled trials
Studies where people are assigned to one of the treatments purely by chance.
Systematic review
A comprehensive evaluation of the available research evidence on a particular topic.
Vascular
The body's network of blood vessels. It includes the arteries, veins, and capillaries that carry blood to and from the heart.

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