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.

RCT Entities:   Population Interventions Outcomes