Triple Therapy Reduces COPD Exacerbation Risk Compared With Dual Therapy

inhalers asthma COPD
Compared with dual therapy, triple therapy was associated with reduced risk for severe exacerbation of COPD and better FEV1.

Individuals with chronic obstructive pulmonary disease (COPD) who receive inhaled corticosteroids (ICS)/long-acting β2-agonists (LABA) benefit significantly from triple therapy, according to a study published in CHEST. By adding a long-acting muscarinic receptor antagonist (LAMA) to ICS/LABA therapy in escalating to triple therapy, the risk for serious adverse events did not rise.

This meta-analysis included 15,519 individuals with COPD from 13 randomized controlled trials sourced from a variety of databases. These studies were of high quality and compared fixed or free ICS/LABA/LAMA triple therapy with fixed or free ICS/LABA dual therapy. Primary end points included the effects of triple therapy compared with dual therapy on risk for severe exacerbation of COPD and serious cardiovascular adverse events, as well as on the change of trough forced expiratory volume in 1 second (FEV1). The comparative effect of the 2 therapies was investigated via a pairwise meta-analysis.

Of the total study population, 53.1% underwent triple therapy and 46.9% underwent dual therapy. Compared with dual therapy, triple therapy was associated with reduced risk for severe exacerbation of COPD (relative risk, 0.78; 95% CI, 0.71-0.85; =.05) and better FEV1 (mean difference, 104.86 mL; 95% CI, 86.74-122.99; <.001). In approximately every 4 individuals in the triple therapy group, 1 experienced an increase in FEV1 by ≥100 mL, and ~23 had to be treated with triple therapy for 1 year to avoid 1 severe COPD exacerbation. Serious adverse events were not associated with triple vs dual therapy (relative risk, 0.85; 95% CI, 0.60-1.20; =.27).

Study quality, interagent inconsistency, and duration of treatment in triple therapy compared with individuals who functioned as active comparators proved to be limitations of this study because they modified the treatment effect.

“Triple therapy provides significant clinical benefit in COPD patients on ICS/LABA combination. ICS/LABA therapy can be escalated to triple therapy without a real risk [of] increas[ing] cardiovascular [serious adverse events] when a LAMA is added to the combination,” the researchers concluded.

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Disclosures: This study received funding from University of Rome. Several authors report associations with pharmaceutical companies. For a full list of author disclosures, please see the reference.


Calzetta L, Cazzola M, Matera MG, Rogliani P. Adding a LAMA to ICS/LABA therapy: a meta-analysis of triple therapy in COPD [published online January 17, 2019]. CHEST. doi:10.1016/j.chest.2018.12.016