title: Review of clinical experience with xamoterol. Effects on exercise capacity and symptoms in heart failure.
abstract: The sympathetic nervous system becomes activated in heart failure, and while this is initially beneficial, the consequences of prolonged raised levels of catecholamines can be counterproductive. Xamoterol, a partial agonist that acts on the cardiac beta 1-adrenergic receptor, modifies the response of the heart to variations in sympathetic activity. At rest, it produces modest improvements in cardiac contractility, relaxation, and filling without increase in myocardial oxygen demand. The improvements are maintained during exercise although the attendant tachycardia is attenuated. The beneficial effects of xamoterol on both systolic and diastolic function suggested that it would be effective in patients with mild-to-moderate heart failure, and this was demonstrated in small placebo-controlled studies where effort tolerance and symptoms were improved. A large multicenter study program comprised of four studies demonstrated that patients with mild-to-moderate heart failure randomized to xamoterol (n = 617) 200 mg b.i.d. for 3 months significantly (p less than 0.0001) improved exercise capacity by 37% as compared with the placebo group (n = 300) with an increase of 18%. The xamoterol group also showed significant improvements in symptoms of breathlessness, fatigue, and life values as compared with the placebo group. In one of the multicenter studies in which 433 patients were randomized to xamoterol (n = 220), placebo (n = 109), and a positive control, digoxin 0.125 mg b.i.d. (n = 104), the percentages of improvement in exercise work were 33%, 5%, and 17%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Medical Research Department, ICI Pharmaceuticals, Macclesfield Park, Cheshire, England.
authors.forename: H F
authors.initials: HF
authors.lastname: Marlow
mesh_terms: D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D004311:Double-Blind Method; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D015337:Multicenter Studies as Topic; D009200:Myocardial Contraction / Q000187:drug effects*; D011412:Propanolamines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D013564:Sympathetic Nervous System / Q000187:drug effects; D017307:Xamoterol
chemical_list: D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D017307:Xamoterol