title: Absence of electrocardiographic findings and improved function with once-daily tiotropium in patients with chronic obstructive pulmonary disease.
abstract: OBJECTIVE
  To examine electrocardiographic findings after short- and long-term tiotropium therapy in patients with chronic obstructive pulmonary disease (COPD), and to establish previously reported symptomatic efficacy.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled, parallel-group study.
  
  
  METHODS
  Twelve outpatient investigational centers in the United States.
  
  
  METHODS
  One hundred ninety-six patients with COPD.
  
  
  METHODS
  Patients received either tiotropium 18 mug once/day or placebo, delivered by the HandiHaler device.
  
  
  RESULTS
  Electrocardiography (predose and 5 min postdose) and 24-hour Holter monitoring were performed at baseline and after 8 and 12 weeks of treatment with tiotropium 18 microg once/day or placebo. Efficacy measures (spirometry, global COPD ratings, scores on the EuroQol Health Questionnaire [EQ-5D], albuterol inhaler as needed) were included to demonstrate that the study population exhibited the characteristic improvements observed in previous tiotropium studies. Mean baseline forced expiratory volume in 1 second (FEV1) was 1.03 L. Mean changes in heart rate from baseline were similar in both groups. No differences were noted in the percentage of patients developing rhythm or conduction abnormalities detected with electrocardiography or Holter monitoring. Frequency of premature beats and mean maximal changes in PR, QRS, QT, QTcB, and QTcF intervals were similar in both groups. No patients developed new-onset QT or QTc intervals greater than 500 msec, and no differences were noted in the percentage of patients developing new QT prolongation less than 30 msec, 30-60 msec, or greater than 60 msec. At 12 weeks, predose and postdose improvements in FEV1 were 184 and 265 ml, respectively, with tiotropium versus placebo (p<0.001). Physician and patient global COPD ratings and the EQ-5D visual analog scale scores were improved with tiotropium (p<0.05); as-needed albuterol was reduced by 25% relative to placebo (p<0.05).
  
  
  CONCLUSIONS
  Tiotropium provided spirometric and symptomatic benefits in patients with COPD and was not associated with evidence of electrocardiographic changes in heart rate, rhythm, QT intervals, or conduction.
authors.affiliation: Pulmonary Consultants of North Idaho, Coeur d'Alene, Idaho 83814, USA. hdomc@imbris.net
authors.forename: Henry
authors.initials: H
authors.lastname: Covelli
authors.forename: Sudipta
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Cara
authors.initials: C
authors.lastname: Cassino
authors.forename: Craig
authors.initials: C
authors.lastname: Conoscenti
authors.forename: Steven
authors.initials: S
authors.lastname: Kesten
mesh_terms: D000368:Aged; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D011788:Quality of Life; D012602:Scopolamine Derivatives / Q000009:adverse effects / Q000627:therapeutic use*; D013147:Spirometry; D000069447:Tiotropium Bromide
chemical_list: D001993:Bronchodilator Agents; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide