Effects of metoprolol CR in patients with ischemic and dilated cardiomyopathy - The randomized evaluation of strategies for left ventricular dysfunction pilot study

Background-Metoprolol provides clinical benefits in patients with congestiv e heart failure (CHF). in this study, we investigated the effects of contro lled-release metoprolol (metoprolol CR) on clinical status, on left ventric ular (LV) volumes and function, and on neurohumoral activation in a large n umber of patients with CHF of mixed causes. Methods and Results-Four hundred twenty-six patients with symptomatic CHF w ere randomized to receive metoprolol CR or placebo for 24 weeks. Metoprolol CR did not affect 6-minute walk distance, New York Heart Association funct ional class, or quality of life. However, there was a significant improveme nt 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 e nd-systolic (+19 +/- 55 mL [placebo] versus -2 +/- 51 mL, P < 0.001) volume s 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-tre ated patients (P = 0.001). Patients receiving metoprolol CR had a greater d ecrease in angiotensin II (P = 0.036) and renin (P = 0.032) levels bur an i ncrease in N-terminal atrial natriuretic peptide and brain natriuretic pept ide 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 exp eriencing the composite outcomes of death or any hospitalization. Conclusions-When added to ACE inhibitors, angiotensin II receptor antagonis ts, or both, the use of metoprolol CR improves ventricular function, reduce s activation of the renin-angiotensin systems, and results in fewer deaths.