Adverse events and cardiovasular effects of vilanterol in paediatric asthma: a systematic review

Abstract

Introduction: Ultra-long-acting β2-agonists (uLABAs) are a recent addition in asthma, but are yet to be included in paediatric guidelines. Given their pharmacology there are concerns around unknown adverse effects (AEs) in children. Aims: To review the safety of uLABA vilanterol (VI) use in paediatric patients, including specifically looking for cardiovascular (CVS) AEs. Methods: The Cochrane Database, clinicaltrials.gov, Medline, EMBASE, Pubmed, CINAHL were queried using keywords (‘asthma’ AND ‘vilanterol OR GW642444 OR Revlar Ellipta’ limited to Results: Three papers were included capturing 510 patients aged 5-11 years. Fourteen trials including patients ≥12 years old were excluded as paediatric data was not reported separately. VI dose (6.25-25mcg) and comparator varied (placebo, fluticasone furoate) therefore quantitative analysis was not performed. Abnormal ECGs were seen in 2(1.6%) placebo patients and in 10(2.5%) VI patients; there was no dose correlation, with those on lower VI doses having more episodes of abnormal ECG. None of these episodes were adverse events or required patients to be removed from the study. The ECG abnormalities were not specified and not clear if they were pre- or post-dose. Other CVS parameters were unremarkable. Follow-up period was of short duration. Adverse events occured in 29% of the VI group, 24% of the placebo group and 8% on comparator drugs. Conclusion: With only 510 children recruited, the power to detect rare or uncommon side effects is insufficient. We have highlighted the limitations of CVS monitoring in these studies. This area requires urgent attention and further study in our paediatric patients.