Chronically inhaled salmeterol improves pulmonary function in heart failure.
Inhaled beta-agonists are commonly prescribed for the symptoms of exercise intolerance in heart failure despite a paucity of data regarding their safety and efficacy. This was a prospective, randomized, double-blind, double-dummy, placebo-controlled 14-day cross-over study to determine if chronic inhaled salmeterol therapy 84 microg every 12 hours improved pulmonary function without augmentation of neurohormonal systems or ventricular ectopy in 8 symptomatic heart failure subjects with left ventricular ejection fraction (LVEF) <40% and FEV1 <or=80%. The primary endpoint was FEV1, and the secondary endpoints were forced vital capacity (FVC), forced expiratory flow (FEF25-75), peak expiratory flow rate (PEFR), blood pressure, heart rate, rate-pressure product, plasma norepinephrine, plasma epinephrine, plasma renin activity, percent ventricular ectopy, and salmeterol pharmacokinetics. Salmeterol was associated with a significant 6% improvement in FEV1 compared with placebo (salmeterol 2.46 +/- 0.73 vs. placebo 2.33 +/- 0.73 L, p = 0.01). There was no significant difference in FVC, FEF25-75, and PEFR. Salmeterol increased mean rate-pressure product by 5% (salmeterol 8878 +/- 1560 vs. placebo 8414 +/- 1440 bpm x mm Hg, p = 0.04), although no increase in plasma norepinephrine, epinephrine, plasma renin activity or ventricular ectopy was detected. The Tmax, Cmax, and half-life of salmeterol at steady-state were 5 min, 715 pg/ml and 11.4 hours, respectively. Inhaled salmeterol significantly improves FEV1 without producing measurable effects on neuroactivation or ventricular ectopy. Inhaled salmeterol causes minor increases in rate-pressure product, whose clinical significance remains to be determined. The plasma half-life of salmeterol may be prolonged in heart failure patients, thus leading to accumulation at steady-state.
Ng
Tien M H
TM
Department of Pharmacy Practice, University of Utah Health Sciences Center, Salt Lake City, UT, USA. tng@unmc.edu
Munger
Mark A
MA
Lombardi
William L
WL
Doing
Tony H
TH
Ryujin
Darin T
DT
Young
David C
DC
Lugo
Ralph A
RA
D000280:Administration, Inhalation; D000368:Aged; D000369:Aged, 80 and over; D000420:Albuterol / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012129:Respiratory Function Tests / Q000379:methods; D000068299:Salmeterol Xinafoate
D000068299:Salmeterol Xinafoate; D000420:Albuterol