PURPOSE: Inhaled β2-agonists may have an effect on cardiac repolarization. Changes in corrected QT interval (QTc) were compared in subjects with COPD administered nebulized arformoterol (the (R,R)-isomer of the long-acting bronchodilator formoterol) or placebo.
METHODS: Subjects (n=215; mean age 63 yrs, mean predicted FEV1 41%) received nebulized arformoterol (5 μg, 15 μg, or 25 μg) or placebo twice daily for 14 days in a double-blind, randomized trial. 12-Lead ECGs were extracted in triplicate from Holter monitors at 17 timepoints on the first day of the 7-day placebo run-in period (baseline) and on Day 14. ECGs were analyzed in a validated central laboratory using digital methods. QTc was derived from an individual-specific baseline linear regression model (QTc-I) and from Fridericia's formula (QTc-F). We summarized the change from baseline in QTc averaged over 12 hours. The maximum increase at any timepoint on Day 14 from the baseline mean was also determined.
RESULTS: The mean (SD) changes from baseline in QTc-I were −2.9 (8.2) ms in the placebo group and −3.3 (11.0), −0.2 (8.9), and −2.2 (10.5) ms in the arformoterol 5 μg, 15 μg, and 25 μg groups, respectively. The results were similar for QTc-F: −2.5 (12.2), −2.1 (12.3), 0.2 (10.6), and −1.0 (12.9) ms, respectively. The mean maximum changes (SD) in QTc-I were 15.4 (10.5) ms in the placebo group and 16.5 (13.0), 17.3 (9.6), and 15.7 (13.2) ms in the respective arformoterol groups. Similar results were observed for QTc-F: 18.8 (13.0), 19.5 (14.8), 21.3 (11.2), 20.7 (16.3) ms, respectively.
CONCLUSION: In this study, nebulized arformoterol treatment did not prolong mean QTc-I or QTc-F and no difference was observed between placebo and the 3 doses of arformoterol.
CLINICAL IMPLICATIONS: Nebulization with the long-acting bronchodilator arformoterol did not prolong cardiac repolarization.
DISCLOSURE: John Hanrahan, No Product/Research Disclosure Information; Employee Full-time employee of Sepracor Inc.