Triple Therapy Versus Dual Bronchodilation and Inhaled Corticosteroids/Long-Acting β-Agonists in COPD: Accumulating Evidence from Network Meta-Analyses

Abstract

Guidelines are mainly based on evidence of well-designed randomized controlled trials (RCTs), but there are limitations to the transferability of conclusions of RCTs to usual care mainly because the patients enrolled in RCTs are selected and not representative of the population encountered in daily practice; moreover, the research environment is substantially different from that of the real world. Because of the scarcity of data generated in large unselected populations in everyday clinical practice, the possibility of using meta-analyses can be considered. Recently, several meta-analyses have attempted to clarify the role of triple therapy containing a long-acting b-agonist (LABA), a long-acting muscarinic antagonist

Adding a Second Bronchodilator in COPD: A Meta-Analysis on the Risk of Specific Cardiovascular Serious Adverse Events of Tiotropium/Olodaterol Fixed-Dose Combination

“…Meta-analyses, as well as RCTs and observational studies, are characterized by intrinsic limitations [45][46][47]. Thus, taken together the results of this meta-analysis along with those of the current evidences raised from large RCTs and large observational studies, the results of this research should be interpreted by clinicians in agreement with the medical characteristics of each COPD patient.…”

<p>Clinical and Economic Consequences of Inhaled Corticosteroid Doses and Particle Size in Triple Inhalation Therapy for COPD: Real-Life Study</p>

“…1,2,9,12 Some reviews show that triple therapy provides modest clinical benefits in the general COPD population, while achieving greater efficacy in patients with frequent exacerbations and eosinophilia (asthma-COPD phenotype). 12,21,22 Conversely, adding a LAMA to an IC/ LABA combination produces significant clinical benefits in COPD patients (dual bronchodilation). 21,22 Most studies highlight the discrepancies between the guideline recommendations and the therapy used in clinical practice.…”

“…12,21,22 Conversely, adding a LAMA to an IC/ LABA combination produces significant clinical benefits in COPD patients (dual bronchodilation). 21,22 Most studies highlight the discrepancies between the guideline recommendations and the therapy used in clinical practice. 9,12,21,22 There is debate on the side effects, such as pneumonia and systemic adverse effects, of long-term IC use.…”

“…21,22 Most studies highlight the discrepancies between the guideline recommendations and the therapy used in clinical practice. 9,12,21,22 There is debate on the side effects, such as pneumonia and systemic adverse effects, of long-term IC use. Some reports suggest the safety profile of IC depends on the dose administered.…”

Triple Combination Inhalers in Chronic Obstructive Pulmonary Disease and Asthma

“…[10][11][12][13][14][15][16] In particular, the IMPACT study (Informing the Pathway of COPD The step-up approach from dual bronchodilation to triple therapy, proposed by the GOLD strategy, 1 does not reflect the important differences in COPD exacerbations (they differ in etiology, severity, and biological substrate) and therefore, is not adapted to the specific needs of the patient to be treated. 21 The already mentioned post-hoc analysis of the IMPACT study documented that a treatment including an ICS in patients with COPD with higher eosinophilia is more effective in the prevention of exacerbations that required oral corticosteroids and/or are not associated with bacterial infections. 20 On the contrary, adding a LAMA to an ICS/LABA combination induces significant clinical benefits in the general population with COPD and reduces the risk of moderate or severe exacerbations regardless of the blood eosinophil count, without increasing the risk of serious cardiovascular adverse events that may always be possible when a LAMA is added.…”