EFFECTS OF CARVEDILOL, A VASODILATOR-BETA-BLOCKER, IN PATIENTS WITH CONGESTIVE-HEART-FAILURE DUE TO ISCHEMIC-HEART-DISEASE

Background beta-Blocker therapy has been shown to increase ejection fr action in patients with heart failure of idiopathic etiology. However, in patients with heart failure of ischemic etiology, the effects of t his treatment on left ventricular function remain uncertain, as do the effects on exercise performance and symptoms. Methods and Results Thi s study investigated the effects of carvedilol, a beta-blocker with al pha(1)-blocking properties, on left ventricular size and function, max imal 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 carvedilo l, patients were randomized to continued treatment with carvedilol (up to 25 mg BID) or to matching placebo. After 6 months, left ventricula r ejection fraction measured by radionuclide ventriculography had incr eased by 5.2% (2P<.0001) in the carvedilol group compared with the pla cebo group, and left ventricular end-systolic and end-diastolic dimens ions measured by two-dimensionally guided M-mode echocardiography had decreased by 2.6 mm (2P=.0005) and 1.3 mm (2P=.05), respectively. Ther e 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 main tained with a 23% lower rate-pressure product. Symptoms assessed by th e New York Heart Association (NYHA) scale and the Specific Activity Sc ale (SAS) were unchanged in two thirds of patients in both groups, but there was a small excess of patients whose symptoms worsened and a de ficit of patients whose symptoms improved among those assigned carvedi lol (NYHA, 2P=.05; SAS, 2P=.02). Conclusions In patients with heart fa ilure of ischemic etiology, 6-month treatment with carvedilol improved left ventricular function and maintained exercise performance at a lo wer rate-pressure product, but symptoms assessed by functional class w ere slightly worsened. A larger-scale trial is now required to determi ne whether this treatment will reduce serious morbidity and mortality from heart failure.