Cardiac safety of formoterol 12 microg twice daily in patients with chronic obstructive pulmonary disease.
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.
Campbell
Sammy C
SC
Arizona Respiratory Center, University of Arizona and Pulmonary Section, VA Medical Center, Southern Arizona VA Health Care System, Tucson, AZ, USA. sammycampbell@cox.net
Criner
Gerard J
GJ
Levine
Bernard E
BE
Simon
Stuart J
SJ
Smith
Jonathan S
JS
Orevillo
Chadwick J
CJ
Ziehmer
Barbara A
BA
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
D001993:Bronchodilator Agents; D004983:Ethanolamines; D000068759:Formoterol Fumarate