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)