Safety of indacaterol in the treatment of patients with COPD

Abstract

Purpose: Pooled data were analyzed to evaluate the safety and tolerability of indacaterol, a once-daily inhaled long-acting β(2)-agonist for chronic obstructive pulmonary disease (COPD).

Patients and methods: Data 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.

Results: The 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 β(2)-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).

Conclusion: Indacaterol has a good profile of safety and tolerability that is appropriate for the maintenance treatment of patients with COPD.

Keywords: formoterol; indacaterol; safety; salmeterol; tiotropium; tolerability.

Figure 1

Risk of major adverse cardiovascular events (MACE) (myocardial infarction, stroke and cardiovascular death) relative to placebo, adjusted for length of time on treatment. (A) “Broad MACE” includes all preferred terms relating to myocardial infarction, cerebrovascular events, and nervous system hemorrhages; (B) “custom MACE” is a more focused subset of broad MACE including those preferred terms best describing myocardial infarction and stroke. (For the terms in each category, see Tables S3 and S4 in Supplementary material.) Abbreviation: CI, confidence interval.

Figure 2

Risk of death relative to placebo, adjusted for length of time on treatment. Abbreviation: CI, confidence interval.

Figure 3

Rate of chronic obstructive pulmonary disease exacerbations compared with placebo over 12 months of treatment. Abbreviation: CI, confidence interval.

Figure 4

Mean (95% CI) differences from placebo in plasma potassium, blood glucose, QTc interval, sitting pulse and sitting systolic and diastolic blood pressure (BP) at 1 hour post-dose after 3 months of treatment. Abbreviations: IND, indacaterol; FOR, formoterol; SLM, salmeterol; TIO, tiotropium; CI, confidence interval.