Effects of carvedilol, a vasodilator-beta-blocker, in patients with congestive heart failure due to ischemic heart disease. Australia-New Zealand Heart Failure Research Collaborative Group.

BACKGROUND

beta-Blocker therapy has been shown to increase ejection fraction in patients with heart failure of idiopathic etiology. However, in patients with heart failure of ischemic etiology, the effects of this treatment on left ventricular function remain uncertain, as do the effects on exercise performance and symptoms.

METHODS AND RESULTS

This study investigated the effects of carvedilol, a beta-blocker with alpha 1-blocking properties, on left ventricular size and function, maximal and submaximal exercise performance, and symptoms in 415 patients with stable heart failure of ischemic etiology (ejection fraction < 45%). After a 2- to 3-week run-in phase on open-label low-dose carvedilol, patients were randomized to continued treatment with carvedilol (up to 25 mg BID) or to matching placebo. After 6 months, left ventricular ejection fraction measured by radionuclide ventriculography had increased by 5.2% (2P < .0001) in the carvedilol group compared with the placebo group, and left ventricular end-systolic and end-diastolic dimensions measured by two-dimensionally guided M-mode echocardiography had decreased by 2.6 mm (2P = .0005) and 1.3 mm (2P = .05), respectively. There were no significant changes in either treadmill exercise duration or 6-minute walk distance between carvedilol and placebo groups (both 2P > .1); in the carvedilol group, exercise performance was therefore maintained with a 23% lower rate-pressure product. Symptoms assessed by the New York Heart Association (NYHA) scale and the Specific Activity Scale (SAS) were unchanged in two thirds of patients in both groups, but there was a small excess of patients whose symptoms worsened and a deficit of patients whose symptoms improved among those assigned carvedilol (NYHA, 2P = .05; SAS, 2P = .02).

CONCLUSIONS

In patients with heart failure of ischemic etiology, 6-month treatment with carvedilol improved left ventricular function and maintained exercise performance at a lower rate-pressure product, but symptoms assessed by functional class were slightly worsened. A larger-scale trial is now required to determine whether this treatment will reduce serious morbidity and mortality from heart failure.