25135743
BACKGROUND	To further assess the safety profile of the fixed-dose combination of indacaterol and glycopyrronium ( QVA149 ) and its monocomponents ; we investigated the impact of individual patient-level factors and time by integrating the patient-level safety data from the QVA149 clinical programme with relevant information from the independent indacaterol and glycopyrronium safety databases .
METHODS	Data from 11,404 patients with chronic obstructive pulmonary disease ( COPD ) were pooled from 14 clinical studies of QVA149 , indacaterol and glycopyrronium of 3 month 's duration with at least two of the treatment groups : QVA149 110/50g , glycopyrronium 50g , indacaterol 150g , placebo or tiotropium 18g .
METHODS	Overall hazard ratio ( HR ) was assessed between the active treatments and placebo and in various subgroups related to severity of airways obstruction , inhaled corticosteroid use , cardiovascular risk factors , sex , age and body mass index for death , serious cases of cardio - and cerebrovascular ( CCV ) events , major adverse cardiovascular events ( MACEs ) , pneumonia , COPD exacerbations requiring hospitalisation or atrial flutter/fibrillation ( AF/F ) .
RESULTS	The HR for QVA149 versus placebo showed no significant increase in the overall risk for death ( HR [ 95 % confidence interval ] : 0.93 [ 0.34-2 .54 ] ) ; CCV events ( 0.60 [ 0.29-1 .24 ] ) ; MACE ( 1.04 [ 0.45-2 .42 ] ) ; pneumonia ( 1.10 [ 0.54-2 .25 ] ) ; COPD exacerbations ( 0.60 [ 0.40-0 .91 ] ) ; and AF/F ( 1.03 [ 0.49-2 .18 ] ) .
RESULTS	Similar results were observed for indacaterol , glycopyrronium and tiotropium versus placebo for overall risk and in analysed subgroups .
CONCLUSIONS	There was no increase in the risk for the investigated safety endpoints for the fixed-dose combination QVA149 , and it had a comparable safety profile as its monocomponents and tiotropium versus placebo .

