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.

Effect of formoterol fumarate treatment on exercise-induced bronchoconstriction in children.

BACKGROUND: Exercise-induced bronchoconstriction (EIB) is common, particularly in children. OBJECTIVES: To compare the protective effect of single doses of formoterol fumarate via Aerolizer with placebo and albuterol in children with EIB. METHODS: In this randomized, double-blind, double-dummy, crossover trial, 23 children (aged 4-11 years) received formoterol, 12 or 24 microg; albuterol, 180 microg; or placebo at 4 separate visits. Protection against EIB was evaluated as the maximum percentage decrease in forced expiratory volume in 1 second (FEV1) from the preexercise value after exercise challenge tests (6-minute treadmill) conducted 15 minutes and 4, 8, and 12 hours after administration of the dose. RESULTS: The maximum percentage decrease in FEV1 after the 4-hour exercise test (primary efficacy variable) was significantly less for formoterol, 12 and 24 microg, vs placebo (P < .001 for both) or albuterol (P = .016 and .010, respectively); albuterol was not significantly different from placebo. Formoterol, 12 and 24 microg, differed from placebo at 8 hours (P = .002 and .001, respectively), with a smaller difference between albuterol and placebo (P = .045). Rescue medication use and a high dropout rate may have biased treatment differences at later time points. Protection against EIB (<20% maximum decrease in FEV1) across all time points was observed for 17 (77%) of 22 and 17 (74%) of 23 children with formoterol, 12 and 24 microg, respectively, compared with 8 (35%) of 23 with albuterol and 6 (27%) of 22 with placebo. CONCLUSIONS: Single doses of formoterol, 12 or 24 microg, are effective in protecting against EIB in children, affording a statistically significantly greater protective effect than placebo or albuterol.