Rebound phenomena following gradual withdrawal of chronic metoprolol treatment in patients with ischemic heart disease.

Metoprolol or placebo was gradually withdrawn during 1 week in 115 patients participating in a 3-year, double-blind, postinfarction study. During the first month after withdrawal mental symptoms and increased cardiac symptoms occurred significantly more frequently in the metoprolol group. Disabling symptoms requiring reinstitution of treatment were seen in 14 of 58 in the metoprolol group vs 4 of 57 in the placebo group (p less than 0.05). In the metoprolol group, there was a rebound increase of basal heart rate and of the heart rate response to orthostatic testing during 3 weeks after withdrawal, when compared to values obtained 6 months later. In 27 patients plasma catecholamine levels were analyzed during repeated exercise tests and orthostatic provocations. Plasma norepinephrine and epinephrine responses to exercise were reduced 1 week after completion of withdrawal. At this time norepinephrine levels tended to be lower in relation to heart rate at all work loads. Our laboratory findings may be related to increased beta-adrenoceptor responsiveness, but unmasking of ischemic symptoms probably contributed to the clinical findings.