Cardiovascular safety of mometasone/indacaterol and mometasone/indacaterol/glycopyrronium once-daily fixed-dose combinations in asthma: pooled analysis of phase 3 trials.
Administration, Inhalation
Adolescent
Adrenergic beta-2 Receptor Agonists
/ administration & dosage
Adult
Aged
Aged, 80 and over
Asthma
/ drug therapy
Child
Clinical Trials, Phase III as Topic
Drug Therapy, Combination
Female
Glycopyrrolate
/ administration & dosage
Heart Disease Risk Factors
Humans
Indans
/ administration & dosage
Male
Middle Aged
Mometasone Furoate
/ administration & dosage
Quinolones
/ administration & dosage
Randomized Controlled Trials as Topic
Safety
Treatment Outcome
Young Adult
Asthma
Cardiovascular safety
Inhaled corticosteroids (ICS)
Long-acting beta2-agonists (LABA)
Long-acting muscarinic antagonists (LAMA)
Mometasone/indacaterol/glycopyrronium
Journal
Respiratory medicine
ISSN: 1532-3064
Titre abrégé: Respir Med
Pays: England
ID NLM: 8908438
Informations de publication
Date de publication:
Historique:
received:
13
08
2020
revised:
19
01
2021
accepted:
21
01
2021
pubmed:
13
3
2021
medline:
17
12
2021
entrez:
12
3
2021
Statut:
ppublish
Résumé
To evaluate cardiovascular safety of two new inhaled fixed-dose combinations for treatment of asthma: (i) the inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA) mometasone furoate/indacaterol acetate (MF/IND), (ii) the ICS/LABA/long-acting muscarinic antagonist (LAMA) MF/IND/glycopyrronium bromide (GLY). Patient-level data were pooled from four randomized trials, including 52-week studies PALLADIUM (n = 2216) and IRIDIUM (n = 3092), 24-week study ARGON (n = 1426), and 12-week study QUARTZ (n = 802). Cardio-/cerebrovascular (CCV) event frequencies were examined in the following comparisons: (1) LABA effect: pooled-dose MF/IND vs. pooled-dose MF; (2) LAMA effect: pooled-dose MF/IND/GLY vs. pooled-dose MF/IND; (3) ICS-dose effects: (a) high-dose MF/IND vs. medium-dose MF/IND, (b) high-dose MF/IND/GLY vs. medium-dose MF/IND/GLY; (4) intra-class effects: (a) high-dose MF/IND vs. Fluticasone/Salmeterol (F/S), (b) high-dose MF/IND/GLY vs. F/S + Tiotropium (TIO). Risk estimates (percentage of patients with ≥1 CCV event) and risk differences (RDs) with 95% confidence intervals (CIs) were calculated for each comparison. The frequency of CCV events was low, without notable differences between comparison groups. Risk estimates and corresponding RDs (95% CIs) were as follows: (1) pooled-dose MF/IND = 2.35%, pooled-dose MF = 2.18%, RD = 0.17% (-1.00%, 1.34%); (2) pooled-dose MF/IND/GLY = 3.65%, pooled-dose MF/IND = 3.77%, RD = -0.12% (-1.63%, 1.39%); (3a) high-dose MF/IND = 3.69%, medium-dose MF/IND = 3.35%, RD = 0.34% (-1.25%, 1.94%); (3b) high-dose MF/IND/GLY = 2.84%, medium-dose MF/IND/GLY = 2.02%, RD = 0.82% (-0.49%, 2.13%); (4a) high-dose MF/IND = 3.69%, F/S = 2.82%, RD = 0.87% (-0.66%, 2.40%); (4b) high-dose MF/IND/GLY = 1.26%, F/S + TIO = 1.05%, RD = 0.21% (-1.26%, 1.68%). There was no evidence of increased cardiovascular risk attributable to the addition of IND to MF or addition of GLY to MF/IND. Similarly, no evidence of increased cardiovascular risk was observed with an increase in the ICS-dose or relative to F/S ± TIO.
Identifiants
pubmed: 33711782
pii: S0954-6111(21)00017-2
doi: 10.1016/j.rmed.2021.106311
pii:
doi:
Substances chimiques
Adrenergic beta-2 Receptor Agonists
0
Indans
0
Quinolones
0
Mometasone Furoate
04201GDN4R
indacaterol
8OR09251MQ
Glycopyrrolate
V92SO9WP2I
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
106311Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.