In the analysis of trials involving 228,710 patients with stable COPD, triple combination therapy was associated with fewer exacerbations and lower all-cause mortality than other regimens.1

‘To the best of our knowledge, this study is the first to find an effect of mortality reduction by pharmacologic therapy for stable COPD using Bayesian network meta-analysis,’ said authors Chang-Hoon Lee and colleagues.

The researchers queried publication databases, clinical trial registers and pharmaceutical company websites to identify parallel-design randomised controlled trials comparing inhaled single therapy (LAMA, LABA or ICS), combined dual or triple therapy (ICS/LAMA/LABA, LAMA/LABA, or ICS/LABA), or placebo in adults with stable COPD, with a study duration of at least 12 weeks.

They used Bayesian statistical methods, which can be used to compare treatment efficacy in the absence of head-to-head comparison studies. This approach can provide probability statements ‘related to one drug being better than another and probability calculations of which drugs are best’.

Exacerbation risk

Compared with placebo, all regimens were associated with significantly reduced risk of overall exacerbations and moderate to severe exacerbations.

ICS/LAMA/LABA was the most efficacious treatment for reducing the exacerbation risk, with an odds ratio (OR) of 0.57 versus placebo (95% credible interval [CrI] 0.50–0.64; posterior probability of OR > 1 [p(OR > 1)] < 0.001). In addition, and in contrast to the other drug classes, ICS/LAMA/LABA and ICS/LABA were associated with a significantly higher probability of reduced mortality than placebo (OR 0.74, 95% CrI 0.59–0.93, p[OR > 1] = 0.004; and OR 0.86, 95% CrI 0.76–0.98, p[OR > 1] = 0.015, respectively).

ICS/LAMA/LABA and ICS/LABA did not significantly reduce cardiovascular mortality compared with LAMA or placebo.

The meta-analysis also examined safety of the regimens. All ICS-containing regimens were linked to a significantly increased risk of pneumonia, with an OR of 1.56 for ICS/LAMA/LABA triple therapy (95% CrI 1.19–2.03, p[OR > 1] = 1.000).

The authors acknowledge that their analysis included only a small number of studies conducted in less symptomatic patients or patients at low risk of exacerbations. They say further studies are needed to determine whether any specific subgroup can benefit particularly from triple therapy.

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