Cardiovascular safety of mometasone/indacaterol and mometasone/indacaterol/glycopyrronium once-daily fixed-dose combinations in asthma: pooled analysis of phase 3 trials.

Abstract

OBJECTIVE\nTo 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).\n\n\nMETHODS\nPatient-level data were pooled from four randomized trials, including 52-week studies PALLADIUM (n\xa0=\xa02216) and IRIDIUM (n\xa0=\xa03092), 24-week study ARGON (n\xa0=\xa01426), and 12-week study QUARTZ (n\xa0=\xa0802). 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\xa0+\xa0Tiotropium (TIO). Risk estimates (percentage of patients with ≥1 CCV event) and risk differences (RDs) with 95% confidence intervals (CIs) were calculated for each comparison.\n\n\nRESULTS\nThe 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\xa0=\xa02.35%, pooled-dose MF\xa0=\xa02.18%, RD\xa0=\xa00.17% (-1.00%, 1.34%); (2) pooled-dose MF/IND/GLY\xa0=\xa03.65%, pooled-dose MF/IND\xa0=\xa03.77%, RD\xa0=\xa0-0.12% (-1.63%, 1.39%); (3a) high-dose MF/IND\xa0=\xa03.69%, medium-dose MF/IND\xa0=\xa03.35%, RD\xa0=\xa00.34% (-1.25%, 1.94%); (3b) high-dose MF/IND/GLY\xa0=\xa02.84%, medium-dose MF/IND/GLY\xa0=\xa02.02%, RD\xa0=\xa00.82% (-0.49%, 2.13%); (4a) high-dose MF/IND\xa0=\xa03.69%, F/S\xa0=\xa02.82%, RD\xa0=\xa00.87% (-0.66%, 2.40%); (4b) high-dose MF/IND/GLY\xa0=\xa01.26%, F/S\xa0+\xa0TIO\xa0=\xa01.05%, RD\xa0=\xa00.21% (-1.26%, 1.68%).\n\n\nCONCLUSIONS\nThere 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\xa0±\xa0TIO.