Effect of Metoprolol CR/XL on Exercise Tolerance in Chronic Heart Failure — a Substudy to the MERIT-HF Trial

BACKGROUND: Beta-blockade usually causes a slight reduction in exercise capacity among healthy subjects, while more variable results have been observed in chronic heart failure (CHF), probably related to patients studied, methods and agent used. The effect of metoprolol controlled release/extended release (CR/XL) on peak oxygen uptake (peak VO(2)) in this patient population has not previously been investigated. AIMS: We examined the effect of long-term treatment with the selective beta(1)-receptor blocker metoprolol CR/XL once daily on exercise capacity in patients with CHF. METHODS: Ninety-four patients (70 males and 24 females; mean age 63.6+/-10.6 years) with chronic symptomatic heart failure in New York Heart Association (NYHA) functional class II-IV, and with ejection fraction <or=40%, stabilized on optimum standard therapy were randomized to metoprolol CR/XL or placebo in a double-blind trial. Exercise capacity was evaluated by peak VO(2) at baseline, after 3 months and at the end of study (mean follow-up 11.4+/-0.4 months). RESULTS: Compared with placebo metoprolol CR/XL produced a significant decrease in heart rate by 11 beats/min at rest and 18 beats/min at peak exercise. There was a tendency for a temporal decline in peak VO(2) after 3 months of therapy in both groups, but altogether peak VO(2) remained unchanged from baseline with no difference between the groups at 1 year. CONCLUSIONS: In patients with moderate to severe CHF, 11.4 months of beta(1)-blockade with metoprolol CR/XL had no effect on exercise capacity when compared with placebo or baseline.