title: Eletrocardiographic monitoring in COPD patients receiving tiotropium.
abstract: Tiotropium is a once-daily, inhaled anticholinergic for the treatment of chronic obstructive pulmonary disease that acts as a prolonged antagonist of the M3-receptor. To ascertain whether electrophysiologic effects can be detected following tiotropium treatment in patients with chronic obstructive pulmonary disease, serial electrocardiograms were incorporated into multiple placebo-controlled clinical trials including long-term (6 and 12-month) trials with tiotropium 18 mcg daily (n=2,128) and a 4-week dose-ranging study with tiotropium up to 36 mcg daily (n= 169). In addition, 24-hour electrocardiographic (Holter) monitoring was performed as part of a 6-week, placebo-controlled trial with tiotropium 18 mcg daily (n= 121). Electrocardiograms were performed before and up to 6 times during treatment in the 12-month trials, and before and at the end of treatment in the 6-month trials. For both the 12 and 6-month trials, electrocardiograms were recorded as adverse events if significant changes occurred, and were retrospectively sent for centralized analysis. During the 6-week trial, Holter monitoring was performed prior to the first dose and following 6 weeks of treatment. In all of these trials, no significant differences were observed in any of the electrocardiogram or Holter outcome parameters compared to placebo. Specifically, there was no clinically relevant difference in heart rate, atrio-ventricular conduction or the occurrence of ventricular or supraventricular arrhythmias. In conclusion, tiotropium was not associated with any signs of cardiac safety concerns as defined by electrocardiographic evaluations in placebo-controlled clinical trials.
authors.affiliation: University of Pennsylvania, eResearch Technology, Inc., Gladwyne, Pennsylvania 19035, USA. JMorganroth@ert.com
authors.forename: Joel
authors.initials: J
authors.lastname: Morganroth
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Golisch
authors.forename: Steven
authors.initials: S
authors.lastname: Kesten
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015716:Electrocardiography, Ambulatory; D005500:Follow-Up Studies; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology*; D012189:Retrospective Studies; D012602:Scopolamine Derivatives / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D000069447:Tiotropium Bromide; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide