Chronically Inhaled Salmeterol Improves Pulmonary Function in Heart Failure

Abstract

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.

Heart Failure and Chronic Obstructive Pulmonary Disease

“…All studies involving nebulized or inhaled beta-agonists were included (30)(31)(32). Given the unequivocal results of large randomized controlled trials investigating xamoterol (33,34), we restricted further inclusion of oral beta-agonists to larger studies lasting at least 1 month (35).…”

Pharmacological modulation of β-adrenoceptor function in patients with coexisting chronic obstructive pulmonary disease and chronic heart failure

“…Whatever the case may be, the observation that β 2 -agonists may exacerbate heart failure is supported by physiologic observations. Although the possibility that β 2 -agonists might exacerbate heart failure, Ng et al [51] explored if chronic inhaled salmeterol therapy, 100 µg bid, improved pulmonary function without augmentation of neurohormonal systems or ventricular ectopy in symptomatic heart failure subjects with LV ejection fraction <40%. Salmeterol significantly increased mean rate-pressure product by 5%, and FEV 1 without producing measurable effects on neuroactivation or ventricular ectopy.…”

Using the Lower Limit of Normal Instead of the Conventional Cutoff Values to Define Predictors of Pulmonary Function Impairment in Subjects With Chronic Heart Failure

“…[8][9][10][11][12] Moreover, pulmonary function impairment increases with the severity of heart failure, 9,11 provides important prognostic information, [39][40][41][42] and may ameliorate or normalize with several treatment modalities, such as pharmacologic and nonpharmacologic treatment of heart failure 2,28,43-46 and antiobstructive therapy with bronchodilators. [47][48][49][50][51][52][53] Pulmonary function might thus be used as a guide for the evaluation of patients with chronic heart failure, with respect to severity of disease, prognosis, and response to treatment.…”