PURPOSE: As COPD patients commonly suffer cardio- and cerebrovascular (CCV) co-morbidities, our purpose was to establish the CCV safety profile of indacaterol, a novel, inhaled, long-acting β(2)-agonist for COPD. METHODS: The indacaterol clinical trial database comprised 4635 patients with moderate-to-severe COPD enrolled into studies of ≥6 months' duration treated with indacaterol, placebo or other bronchodilators (formoterol, salmeterol, tiotropium). Adverse events (AEs) were analysed overall and according to Anti-Platelet Trialists' Collaboration (APTC) criteria and baseline cardiovascular risk factors. A subset of patients had Holter monitoring. RESULTS: Compared with placebo, indacaterol did not increase the risk of CCV AEs; relative risks were not significantly different for indacaterol versus other treatments. In all treatment groups, including placebo, most CCV AEs occurred in patients with pre-existing cardiovascular risk factors. The risk of APTC events (e.g. myocardial infarction, stroke, cardiovascular-related death) was not significantly increased for indacaterol versus placebo. The incidence of notable QTc interval increases >60 ms was low with all active treatments (0-0.5%, versus 0.3% with placebo). Holter monitoring in the subset of patients receiving indacaterol, tiotropium or placebo showed no clinically relevant effect of indacaterol or tiotropium relative to placebo on the development of arrhythmias. The number of deaths adjusted for exposure was lower with all active treatments than with placebo, with a trend to reduced risk with indacaterol (relative risk 0.30, p = 0.054). CONCLUSION: The overall CCV safety profile of indacaterol was similar to placebo and comparable with other long-acting bronchodilators, providing reassurance for regular long-term use of indacaterol in COPD. Data for this analysis were pooled from three studies, registered at ClinicalTrials.gov as: NCT00393458, NCT00463567 and NCT00567996.
PURPOSE: As COPD patients commonly suffer cardio- and cerebrovascular (CCV) co-morbidities, our purpose was to establish the CCV safety profile of indacaterol, a novel, inhaled, long-acting β(2)-agonist for COPD. METHODS: The indacaterol clinical trial database comprised 4635 patients with moderate-to-severe COPD enrolled into studies of ≥6 months' duration treated with indacaterol, placebo or other bronchodilators (formoterol, salmeterol, tiotropium). Adverse events (AEs) were analysed overall and according to Anti-Platelet Trialists' Collaboration (APTC) criteria and baseline cardiovascular risk factors. A subset of patients had Holter monitoring. RESULTS: Compared with placebo, indacaterol did not increase the risk of CCV AEs; relative risks were not significantly different for indacaterol versus other treatments. In all treatment groups, including placebo, most CCV AEs occurred in patients with pre-existing cardiovascular risk factors. The risk of APTC events (e.g. myocardial infarction, stroke, cardiovascular-related death) was not significantly increased for indacaterol versus placebo. The incidence of notable QTc interval increases >60 ms was low with all active treatments (0-0.5%, versus 0.3% with placebo). Holter monitoring in the subset of patients receiving indacaterol, tiotropium or placebo showed no clinically relevant effect of indacaterol or tiotropium relative to placebo on the development of arrhythmias. The number of deaths adjusted for exposure was lower with all active treatments than with placebo, with a trend to reduced risk with indacaterol (relative risk 0.30, p = 0.054). CONCLUSION: The overall CCV safety profile of indacaterol was similar to placebo and comparable with other long-acting bronchodilators, providing reassurance for regular long-term use of indacaterol in COPD. Data for this analysis were pooled from three studies, registered at ClinicalTrials.gov as: NCT00393458, NCT00463567 and NCT00567996.
Authors: Robert A Wise; Kenneth R Chapman; Benjamin M Scirica; David A Schoenfeld; Deepak L Bhatt; Sami Z Daoud; Beatriz Seoane; Colin Reisner; Esther Garcia Gil Journal: Chronic Obstr Pulm Dis Date: 2018-01-24