Comparison of the effects of dual and single bronchodilators in COPD patients relocated from group D to group B by the revised 2017 GOLD classification: a post-hoc pooled analysis of global RCTs

Comparison of the effects of dual and single bronchodilators in COPD patients relocated from group D to group B by the revised 2017 GOLD classification: a post-hoc pooled analysis of global RCTs

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. For its treatment, bronchodilators are the most important pharmacological agents. These medications which usually used in the form of an inhaler relax smooth muscles of the airways and help relieve shortness of breath. Two types of bronchodilators with different mechanisms of action are used for the treatment of COPD: beta-2 agonist, and muscarinic antagonist. A beta-2 agonist activates beta adrenergic receptors of smooth muscles leading to dilation of the airways (bronchodilation). A muscarinic antagonist blocks muscarinic cholinergic receptors and produces bronchodilation. During the recent years, combinations of these two distinct types of bronchodilator, called as dual bronchodilators (fixed-dose combinations of long-acting beta-2 agonist and long-acting muscarinic antagonist) have been introduced in the market from several pharmaceutical companies.Although efficacy and safety of dual bronchodilators compared with single bronchodilators have been shown, not every patient with COPD is treated with dual bronchodilators. The most widely used COPD guidelines recommend that a certain group of patients be treated with a dual bronchodilator as an initial medication and others start their medication with a single bronchodilator. The distinction between groups was made based on lung function, number of acute deteriorating events (i.e., acute exacerbation) in the preceding year, and patients' symptoms. The recent revision of the guidelines in 2017 has removed lung function from the grouping criteria; and this change has caused a reduction in the number of patients whose initial recommended choice of treatment is a dual bronchodilator. In other words, some patients who would have been indicated for and benefited from use of dual bronchodilators if the classification system had not been revised are now prescribed with a single bronchodilator. It is regrettable for physicians to see a decrease in the number of patients who may benefit from dual bronchodilators, as they are more potent than single bronchodilators. We aimed to determine the role of dual bronchodilators in patients who are not indicated for dual bronchodilators by the 2017 revised guidelines but who would have been indicated for them by the previous guidelines. The hypothesis is that early use of dual bronchodilators would improve lung function, improve patient-reported outcomes, and decrease the occurrence of acute exacerbations.

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[DYNAGITO]" },{ "PostingID": 16129, "Title": "NOVARTIS-CQVA149A2303", "Description": "A 26-week Treatment Multi-center, Randomized, Double-blind, Parallel-group, Placebo and Active Controlled (Open Label) Study to Assess the Efficacy, Safety and Tolerability of QVA149 (110/50 μg q.d.) in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)" },{ "PostingID": 16130, "Title": "NOVARTIS-CQVA149A2339", "Description": "A Placebo and Active Controlled Study to Assess the Long-term Safety of Once Daily QVA149 for 52 Weeks in Chronic Obstructive Pulmonary Disease (COPD) Patients With Moderate to Severe Airflow Limitation" },{ "PostingID": 16131, "Title": "NOVARTIS-CQVA149A2336", "Description": "A 12-week Treatment, Multi-center, Randomized, Double-blind, Parallel-group, Placebo and Active Controlled Study to Assess the Efficacy, Safety, and Tolerability of Indacaterol Maleate / Glycopyrronium Bromide in COPD Patients With Moderate to Severe Airflow Limitation." },{ "PostingID": 16132, "Title": "NOVARTIS-CQVA149A2337", "Description": "A 12-week Treatment, Multi-center, Randomized, Double-blind, Parallel-group, Placebo and Active Controlled Study to Assess the Efficacy, Safety, and Tolerability of Indacaterol Maleate / Glycopyrronium Bromide in COPD Patients With Moderate to Severe Airflow Limitation" },{ "PostingID": 16133, "Title": "NOVARTIS-CQVA149A2304", "Description": "A 64-week Treatment, Multi-center, Randomized, Double-blind, Parallel-group, Active Controlled Study to Evaluate the Effect of QVA149 (110/50 μg o.d.) vs NVA237 (50 μg o.d.) and Open-label Tiotropium (18 μg o.d.) on COPD Exacerbations in Patients With Severe to Very Severe Chronic Obstructive Pulmonary Disease (COPD)" },{ "PostingID": 16134, "Title": "NOVARTIS-CQVA149A1301", "Description": "A 52-week Treatment, Multi-center, Randomized, Open Label, Parallel Group Study to Assess the Long Term Safety and Tolerability of QVA149 (110 Mcg Indacaterol / 50 Mcg Glycopyrrolate o.d.) Using Tiotropium (18 Mcg o.d.) as an Active Control in Japanese Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)" },{ "PostingID": 16135, "Title": "NOVARTIS-CQVA149A2307", "Description": "A Multicener, Randomised, Double-blind, Placebo-controlled Study, to Assess the Long Term Safety of 52 Weeks Treatment With QVA149 (110 ug Indacaterol/50ug Glycopyrrolate) in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)" },{ "PostingID": 16137, "Title": "NOVARTIS-CQVA149A2340", "Description": "A Multi-centre Randomized Double Blind 52-week Study to Assess the Safety of QVA149 Compared to QAB149 in Patients With COPD Who Have Moderate to Severe Airflow Limitation" }]

Kang, J., Lee, J.S., Lee, S.W. et al. Dual versus monotherapy with bronchodilators in GOLD group B COPD patients according to baseline FEV1 level: a patient-level pooled analysis of phase-3 randomized clinical trials. Respir Res 22, 55 (2021)
https://doi.org/10.1186/s12931-021-01648-5