title: Cardiac safety of formoterol 12 microg twice daily in patients with chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Some evidence suggests an increased risk of myocardial infarction and dysrhythmia events associated with beta(2)-agonist use in patients with chronic obstructive pulmonary disease (COPD). This prospective, multicenter, randomized, double-blind, placebo-controlled study compared the cardiac safety of formoterol and placebo in patients with COPD.
  
  
  METHODS
  After a 3-14-day run-in, 204 patients were randomized to receive formoterol 12 microg dry powder inhalation or matching placebo twice daily for 8 weeks. Twenty four-hour continuous electrocardiography (Holter monitoring) was performed at screening and after 2 and 8 weeks of treatment.
  
  
  RESULTS
  Only a small number of patients met the predefined criteria for a proarrhythmic event (4 formoterol and 2 placebo patients). No patients had sustained postbaseline ventricular tachycardia events, postbaseline run of ventricular ectopic beats associated with relevant symptoms (e.g. hypotension, syncope), or an episode of ventricular flutter or fibrillation. Holter monitoring data were variable but showed no clinically meaningful differences between the formoterol and placebo groups, respectively, for variables such as (mean+/-SD at end of treatment): heart rate (80+/-8.6 vs. 80+/-10.6 bpm), number and rate of ventricular premature beats (total 732+/-2685.4 vs. 650+/-2090.6; rate 35+/-131.0 vs. 30+/-101.3 per h), ventricular tachycardia events (total 0.4+/-1.70 vs. 1.0+/-9.23; rate 0.02+/-0.082 vs. 0.05+/-0.479 per h), and supraventricular premature beats (total 504+/-1844.1 vs. 823+/-2961.8; rate 22+/-80.6 vs. 37+/-129.6 per h). Vital signs and electrocardiogram data, including corrected QT intervals (Bazett and Fridericia), were similar across treatment groups. The overall adverse event experience was similar in the formoterol (n=26 [27%]) and placebo (n=33 [31%]) groups. The most common adverse events, infections and respiratory events, were expected for this patient population. The incidence of cardiac adverse events was low (1 formoterol and 4 placebo patients).
  
  
  CONCLUSIONS
  The results of this study confirm the good cardiovascular safety profile of formoterol in patients with COPD.
authors.affiliation: Arizona Respiratory Center, University of Arizona and Pulmonary Section, VA Medical Center, Southern Arizona VA Health Care System, Tucson, AZ, USA. sammycampbell@cox.net
authors.forename: Sammy C
authors.initials: SC
authors.lastname: Campbell
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Criner
authors.forename: Bernard E
authors.initials: BE
authors.lastname: Levine
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Simon
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Smith
authors.forename: Chadwick J
authors.initials: CJ
authors.lastname: Orevillo
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Ziehmer
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D015716:Electrocardiography, Ambulatory; D004983:Ethanolamines / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D000068759:Formoterol Fumarate; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D007239:Infections / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D013147:Spirometry; D013575:Syncope / Q000139:chemically induced; D017180:Tachycardia, Ventricular / Q000139:chemically induced; D014693:Ventricular Fibrillation / Q000139:chemically induced
chemical_list: D001993:Bronchodilator Agents; D004983:Ethanolamines; D000068759:Formoterol Fumarate