Long-term cardiovascular safety of salmeterol powder pharmacotherapy in adolescent and adult patients with chronic persistent asthma - A randomized clinical trial

Study objectives: This study investigates the long-term cardiovascular safety of salmeterol powder vs placebo in adolescent and adult patients with mild persistent asthma, Design: Multicenter, randomized, double-blind, placebo-controlled, parallel-group study, Setting: Eighteen US clinical centers. Patients: Three hundred fifty-two patients (greater than or equal to 12 years) with mild persistent asthma (duration greater than or equal to 6 months) requiring pharmacotherapy; with FEV1 of 70 to 90% of predicted and without abnormal EGG/continuous ambulatory ECG (Holter). Interventions: Randomized to twice-daily salmeterol powder (50 mu g) or placebo ria breath-actuated device for 52 weeks. Backup albuterol was available to control asthma symptoms. Measurements and results: Cardiovascular safety was regularly assessed by 12-lead ECG with a 15-s lead II rhythm strip, 24-h continuous ambulatory ECG (Holter) monitoring, serial vital sign measurements, and review of adverse cardiovascular events. No deaths occurred during the I study. No clinically significant between-group differences were observed in pulse rate, ECC QTc interval, median number of ventricular or supraventricular ectopic events, incidence of ventricular ectopic couplets and runs, or incidence of >100 ventricular or supraventricular ectopic events in 24 h, No clinically significant between-group differences were observed in arterial BP or incidence of adverse cardiovascular events. Salmeterol was well tolerated throughout the 52-week study period, with a cardiovascular safety profile similar to that of placebo. Conclusions: Long-term, twice-daily pharmacotherapy with salmeterol powder is safe and is not associated with unfavorable clinically significant changes in cardiac function or increases in cardiovascular adverse effects.