The natural disease course of chronic obstructive pulmonary disease (COPD) is often punctuated by exacerbations: acute events of symptom worsening associated with significant morbidity and healthcare resource utilization; reduced quality of life; and increased risk of hospitalization and death. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommend that patients at risk of exacerbations (GOLD Groups C and D) receive a long-acting muscarinic antagonist (LAMA) or a long-acting β2-agonist (LABA)/LAMA combination, respectively, as preferred initial treatments. The latter recommendation is based on recent trial evidence demonstrating the superior efficacy of a fixed-dose LABA/LAMA over an inhaled corticosteroid (ICS)/LABA in exacerbation prevention. ICS in combination with a LABA is also indicated for prevention of exacerbations, but the use of ICS is associated with an increased risk of adverse events such as pneumonia, and offers limited benefits beyond those provided by LABA or LAMA monotherapy. In this review, we examine evidence from a number of pivotal studies of LABAs and LAMAs, administered as monotherapy or as part of dual or triple combination therapy, with a specific focus on their effect on exacerbations. We also discuss a new proposed treatment paradigm for the management of COPD that takes into account this recent evidence and adopts a more cautious approach to the use of ICS. In alignment with GOLD 2017, we suggest that ICS should be reserved for patients with concomitant asthma or in whom exacerbations persist despite treatment with LABA/LAMA.
Keywords: Dual bronchodilation; ICS; LABA; LAMA; Treatment guidelines; Triple therapy.