Triple inhaler improves mortality in COPD patients and should be used over ICS-LABA
- related: COPD chronic obstructive pulmonary disease
- tags: #permanent
GOLD 2023 discourages ICS-LABA combination as triple therapy has been shown to be superior.1
- IMPACT and ETHOS
In symptomatic patients with moderate to severe COPD and a history of frequent or severe acute exacerbation of COPD (AECOPD), triple inhaled ICS/LABA/LAMA has been shown to improve lung function, symptoms, and health status and to reduce exacerbations and all-cause mortality compared with dual inhaled LABA/LAMA therapy (choice B is correct; choices A, C, and D are incorrect). In this context, frequent is often defined as two or more moderate AECOPD episodes in the past year, while severe is a hospitalization attributable to AECOPD in the past year. Multiple large, randomized controlled trials have reported consistent results supporting the benefits of triple inhaled therapy over either dual LABA/LAMA or ICS/LABA therapy in patients with significant COPD and a history of frequent or severe AECOPD. These benefits include improved lung function, symptoms, health-related quality of life, and exacerbation frequency. Two reports examining all-cause mortality, after gathering and assessing available vital status data in the intention-to-treat population also confirmed a 28% to 49% mortality reduction in favor of ICS/LABA/LAMA vs LABA/LAMA in this population.
Long-term therapy with ICS is associated with adverse consequences such as oral candidiasis, hoarse voice, and skin bruising, as well as an increased incidence of pneumonia, although increased pneumonia rate has not been uniformly documented with all formulations. Importantly, the increased pneumonia rate has not been linked to increased mortality or admission to the hospital. It has also been confirmed that ICS/LABA/LAMA decreases total pneumonia and exacerbation episodes with a favorable benefit–risk profile compared with both LABA/LAMA and ICS/LABA in patients with symptomatic COPD and a history of AECOPD. It is always essential to balance the risks and benefits of any prescribed pharmacotherapy and ensure patients are receiving the most appropriate and effective medications. In this regard, it is prudent to cautiously use or avoid ICS-containing inhaled therapy in individuals with documented repeated pneumonia events and with blood eosinophil counts <100 µg/L.
Acknowledging that COPD is the fourth most common cause of mortality in the United States and the third most common cause of death in the world, it is vital to optimize management actively and change this deadly reality. The beneficial impact of smoking cessation (and preventing individuals from starting smoking), appropriate use of long-term nocturnal noninvasive ventilation, increasing pulmonary rehabilitation availability and participation, and optimizing inhaled therapy should not be underestimated.2
The benefits of triple inhaled therapy (ICS/LABA/LAMA) vs either LABA/LAMA or ICS/LABA in improving lung function and reducing AECOPD in patients with COPD and at risk of future AECOPD are known. However, until recently, the question remained unanswered in patients without a history of frequent AECOPD. It has now been established that in patients with COPD but without a history of frequent AECOPD, inhaled triple therapy provides clinically meaningful improvements in lung function vs ICS/LABA, with statistically significant, but modest, improvements in predose trough FEV1 vs inhaled LABA/LAMA. However, interestingly for this population, inhaled triple therapy also displayed a marked reduction in AECOPD frequency vs LABA/LAMA (risk ratio = 0.48; 95% CI, 0.37-0.64; P < .0001; absolute rate per year, 0.46 ICS/LABA/LAMA vs 0.95 LABA/LAMA), even in this COPD patient population without a history of frequent AECOPD. Pneumonia incidence was low (<2%) and similar across the triple and dual inhaled therapies.
It has been assumed that the primary reason for ICS use in COPD is to reduce the frequency of AECOPD, and this has now been confirmed. But it is important to acknowledge that symptomatic patients may also experience AECOPD even in the absence of a frequent history of AECOPD. Therefore, in addition to supporting the use of triple therapy in patients with high exacerbation risk, there is a significant reduction in the frequency of AECOPD in symptomatic patients without a history of AECOPD, coupled with a statistically significant, albeit modest, improvement in lung function.3