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 safe ty of salmeterol powder vs placebo in adolescent and adult patients with mi ld 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 yea rs) with mild persistent asthma (duration greater than or equal to 6 months ) requiring pharmacotherapy; with FEV1 of 70 to 90% of predicted and withou t abnormal EGG/continuous ambulatory ECG (Holter). Interventions: Randomized to twice-daily salmeterol powder (50 mu g) or pla cebo ria breath-actuated device for 52 weeks. Backup albuterol was availabl e to control asthma symptoms. Measurements and results: Cardiovascular safety was regularly assessed by 1 2-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 clinicall y significant between-group differences were observed in pulse rate, ECC QT c 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 signi ficant 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 t hat of placebo. Conclusions: Long-term, twice-daily pharmacotherapy with salmeterol powder is safe and is not associated with unfavorable clinically significant chang es in cardiac function or increases in cardiovascular adverse effects.