Effects of Indacaterol/Glycopyrronium on Lung Function and Cardiovascular Events in COPD ? Results from a Meta-Analysis

10 Jun, 21

Introduction

Bronchodilators have been the mainstay in the treatment of chronic obstructive pulmonary diseases (COPD). Current guidelines recommend long-acting ?2-agonist/long-acting antimuscarinic (LABA/LAMA) combination therapy in patients who continue to experience dyspnea & exercise intolerance on monotherapy. There is a significant association between COPD and cardiovascular disease. Previous studies have demonstrated a possibility of an increased risk of serious cardiovascular events with bronchodilators.

Aim

This meta-analysis evaluated the efficacy and safety of indacaterol/glycopyrronium (IND/GLY) in patients with COPD.

Method

Study Design

Systematic review and meta-analysis of randomized controlled trials (RCTs)

Treatment Strategy

The systematic review and meta-analysis was performed according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines
PubMed, OVID, Cochrane Library and Web of Science databases were extensively searched
Key words included “indacaterol/glycopyrronium”, “indacaterol/glycopyrrolate”, “IND/GLY”, “QVA149”, “chronic obstructive pulmonary diseases”, “COPD”, “chronic obstructive airway disease”, “chronic obstructive lung disease”

End Points

Acute exacerbation of COPD
Forced expiratory volume in 1 sec (FEV₁)
Incidence of adverse cardiovascular events such as hypertension, atrial fibrillation, myocardial infarction and heart failure.

Results

Meta-analysis included 23 articles, with a total of 21,238 participants.
Cohort comprised patients aged around 60 years, with predicted FEV₁% values ranging between 30 and 80%, and the proportion of smokers ranged from 30 to 50%
The COPD exacerbations were substantially decreased with IND/GLY as compared to placebo; risk ratio (RR) 0.82, p=0.01.
IND/GLY provided greater reduction in COPD exacerbations as compared to most of the other comparative groups, however the difference was not significant (Table 1).

Table 1. Effects of IND/GLY vs other drugs on exacerbations

Groups	RR	P value
IND/GLY vs LABA	0.93	0.28
IND/GLY vs LAMA	0.97	0.61
IND/GLY vs LABA+ICS	0.87	0.08
IND/GLY vs LABA+LAMA	0.94	0.73
IND/GLY vs LABA+LAMA+ICS	1.04	0.26

IND/GLY improved FEV₁ values significantly as compared to placebo and LABA or LAMA groups with a mean difference (MD) of 0.29; p<0.00001 and MD 0.11 L; p<0.00001 respectively.
Risk of hypertension was not significantly different between the IND/GLY group and the comparator groups (IND/GLY vs LABA, RR=1.88, P = 0.09; IND/GLY vs LAMA, RR=1.42, P = 0.08; IND/GLY vs LABA+ICS, RR=1.85, P = 0.23 and IND/GLY vs LABA+LAMA+ICS, RR=1.18, P = 0.70).
The risk of myocardial infarction (IND/GLY vs LAMA or dual therapy, total RR: 1.49, p = 0.28), atrial fibrillation (IND/GLY vs LAMA, RR: 1.62, p = 0.31) and heart failure (IND/GLY vs LAMA, RR: 0.40, p = 0.31) were similar across the groups.

Conclusions

Indacaterol/Glycopyrronium (IND/GLY) treatment was associated with lower incidence of acute exacerbations and slowed down the decline of FEV₁.
IND/GLY did not increase the incidence of adverse cardiovascular events and has an adequate safety profile.

Heart Lung. 2021 July-Aug; 50(4): 532-41. Doi: 10.1183/23120541.00816-2020.