Effects of Metoprolol CR in Patients With Ischemic and Dilated Cardiomyopathy

BACKGROUND: Metoprolol provides clinical benefits in patients with congestive heart failure (CHF). In this study, we investigated the effects of controlled-release metoprolol (metoprolol CR) on clinical status, on left ventricular (LV) volumes and function, and on neurohumoral activation in a large number of patients with CHF of mixed causes. METHODS AND RESULTS: Four hundred twenty-six patients with symptomatic CHF were randomized to receive metoprolol CR or placebo for 24 weeks. Metoprolol CR did not affect 6-minute walk distance, New York Heart Association functional class, or quality of life. However, there was a significant improvement in measures of LV function with an attenuation in the increase in LV end-diastolic (+23+/-65 mL [placebo] versus +6+/-61 mL, P=0.01) and LV end-systolic (+19+/-55 mL [placebo] versus -2+/-51 mL, P<0.001) volumes after 24 weeks of therapy. LV ejection fraction was unchanged (-0.05% or -0.005) in the placebo group but increased by 2. 4% in the metoprolol CR-treated patients (P=0.001). Patients receiving metoprolol CR had a greater decrease in angiotensin II (P=0.036) and renin (P=0.032) levels but an increase in N-terminal atrial natriuretic peptide and brain natriuretic peptide levels (P<0. 01). There were fewer deaths in the group receiving beta-blockers (3. 4% versus 8.1%), and there was a similar number of patients experiencing the composite outcomes of death or any hospitalization. CONCLUSIONS: When added to ACE inhibitors, angiotensin II receptor antagonists, or both, the use of metoprolol CR improves ventricular function, reduces activation of the renin-angiotensin systems, and results in fewer deaths.