707-2 Effects of Carvedilol on Left Ventricular Function and Exercise Performance in Patients with Heart Failure of Ischemic Etiology

Results from several small trials in patients with heart failure of predominantly idiopathic etiology suggest that beta-blocker therapy may improve ventricular function, but the effects on exercise performance remain less certain. To determine the effects of such treatment in patients with heart failure of ischemic etiology, patients with this condition and ejection fraction (EF) <45% were randomized to treatment with carvedilol (12.5-50 mg/day) or placebo. Prior to randomization, 444 patients entered a 2–3 week run-in phase on open label, low-dose carvedilol (6.25-12.5 mg/day). 415 patients (93%) were randomized. Primary outcome variables were radionuclide measurements of EF and measurements of treadmill exercise duration (TED) using a modified Naughton protocol. Secondary outcomes included leftventricular chamber dimensions measured by M-mode echocardiography, submaximal exercise performance assessed from 6 minute walk distance (6 MWD) and NYHA functional class. After 6 months, resting heart rate was reduced by 7.1bpm, and blood pressure was reduced by 5.1/4.5 mmHg in the carvedilol group compared to the placebo group. Results for the main outcomes are shown below as differences between carvedilol and placebo groups after 6 months of follow-up.LV Function and SizeExercise and SymptomsEF+5.0%*TED-23.6 sLVEDD-1.5mm†6 MWD-7.7 mLVESD-2.6 mm*NYHA+0.1*p < 001;†p = 004; all others NS. EF = ejection fraction, LV = left ventricular, EDD = end-diastolic dimension, ESD = end-systolic dimension.In conclusion, 6 months of treatment with carvedilol in patients with ischemic heart failure resulted in improved ejection fraction and reduced LV chamber dimensions. However, there were no detectable changes in maximal or submaximal exercise performance or in NYHA class