Study objectives: This study investigates the long-term
cardiovascular safety of salmeterol powder vs placebo in adolescent and
adult patients with mild persistent asthma.
Multicenter, randomized, double-blind, placebo-controlled,
Setting: Eighteen US clinical
Patients: Three hundred fifty-two patients
(≥ 12 years) with mild persistent asthma (duration ≥ 6 months)
requiring pharmacotherapy; with FEV1 of 70 to 90% of
predicted and without abnormal ECG/continuous ambulatory ECG
Interventions: Randomized to twice-daily
salmeterol powder (50 μg) or placebo via breath-actuated device for
52 weeks. Backup albuterol was available to control asthma
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 study. No clinically significant
between-group differences were observed in pulse rate, ECG 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.
Abbreviations: ANOVA = analysis of variance;
SVE = supraventricular ectopic; VE = ventricular ectopic