Safety of indacaterol in the treatment of patients with COPD

Abstract

PurposePooled data were analyzed to evaluate the safety and tolerability of indacaterol, a once-daily inhaled long-acting β2-agonist for chronic obstructive pulmonary disease (COPD).Patients and methodsData were pooled from clinical studies of 3–12 months’ duration in patients with moderate-to-severe COPD receiving double-blind indacaterol 75 μg (n = 449), 150 μg (n = 2611), 300 μg (n = 1157), or 600 μg once daily (n = 547); formoterol 12 μg twice daily (n = 556); salmeterol 50 μg twice daily (n = 895); placebo (n = 2012); or tiotropium 18 μg once daily, given open label or blinded (n = 1214). Outcomes were adverse events, serious adverse events and deaths, plasma potassium, blood glucose, and QTc interval and vital signs.ResultsThe commonest adverse events with indacaterol were COPD worsening, nasopharyngitis, and headache; most cases were mild or moderate and incidence was generally similar to placebo and other active treatments. The risk of acute respiratory serious adverse events (leading to hospitalization, intubation, or death) was not significantly increased with any of the active treatments compared with placebo. COPD exacerbation rates (analyzed in the intent-to-treat population) were significantly reduced with all active treatments versus placebo. Hazard ratios versus placebo for major cardiovascular adverse events were <1 for all indacaterol doses. Notable values for vital signs and measures of systemic β2-adrenoceptor activity were rare with indacaterol. The number of deaths adjusted per patient-year was lower with indacaterol (all doses combined) than with placebo (relative risk 0.21 [95% confidence interval 0.07–0.660], P = 0.008).ConclusionIndacaterol has a good profile of safety and tolerability that is appropriate for the maintenance treatment of patients with COPD.

Recent advances in COPD disease management with fixed-dose long-acting combination therapies

“…The safety profiles of the QVA149 monocomponents, glycopyrronium and indacaterol have been evaluated in their own respective development programs, and were comparable with those of other long-acting bronchodilators [38,39]. Additionally, the overall cardio-and cerebrovascular safety profile of indacaterol was similar to that of placebo [40].…”

Electrocardiographic abnormalities and cardiac arrhythmias in chronic obstructive pulmonary disease

“…In a retrospective cohort case-control analysis of elderly (≥ 67 years) patients with COPD it was demonstrated that new use of short-and long-acting β-agonists (LABAs) may slightly increase the risk of cardiac arrhythmia [38]. Several trials with COPD patients emphasized that LABAs should be used with caution in patients with pre-existing cardiovascular disease [124,[128][129][130]. However, in a recent systematic review regarding the effect of LABAs on COPD exacerbations and death, Declamer et al concluded that long-term LABA treatment is well tolerated and has an acceptable safety profile, as the incidence of adverse events such as skeletal muscle tremors and palpitations was low (b1%) [131].…”

Is ‘GOLD’ standard for the management of COPD in clinical practice?

“…Donohue et al [34] examined a database of pooled clinical-trial data (all data from studies of ≥12 weeks’ duration) with indacaterol, salmeterol and formoterol. They found that the incidence of worsening COPD with all LABAs was significantly lower than that seen with placebo.…”