RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF CARVEDILOL IN PATIENTS WITH CONGESTIVE-HEART-FAILURE DUE TO ISCHEMIC-HEART-DISEASE

Background In patients with heart failure, beta-blocker therapy improv es left-ventricular function after 3-6 months of treatment, but effect s of such treatment on symptoms and exercise performance are inconsist ent, and the longer-term effects on death and other serious clinical e vents remain uncertain. We have investigated these issues in a double- blind, placebo-controlled, randomised trial of the beta-adrenergic blo cker carvedilol (which also has alpha(1)-blocking properties). Methods 415 patients with chronic stable heart failure were randomly assigned treatment with carvedilol (207) or matching placebo (208), At baselin e, 6 months, and 12 months, we measured left-ventricular ejection frac tion, left-ventricular dimensions, treadmill exercise duration, 6 min walk distance, New York Heart Association (NYHA) class, and specific a ctivity scale ISAS) score. Double-blind followup continued for an aver age of 19 months, during which all deaths, hospital admissions, and ep isodes of worsening heart failure were documented, Findings After 12 m onths, left-ventricular ejection fraction had increased by 5.3% (2p<0. 0001) and end-diastolic and end-systolic dimensions had decreased by 1 .7 mm (2p=0.06) and 3.2 mm (2p=0.001), respectively, in the carvedilol group compared with the placebo group. During the same period that we re no clear changes in treadmill exercise duration, 6 min walk distanc e, NYHA class, or SAS score, After 19 months, the frequency of episode s of worsening heart failure was similar in the carvedilol and placebo groups (82 vs 75; relative risk 1.12 [95% CI 0.82-1.53]) but the rate of death or hospital admission was lower in the carvedilol group than in the placebo group (104 vs 131; relative risk 0.74 [0.57-0.95]). In terpretation The beneficial effects of carvedilol on left-ventricular function and size were maintained for at least a year after the start of treatment, but carvedilol had no effect on exercise performance, sy mptoms, or episodes of worsening heart failure. There was an overall r eduction in events resulting in death or hospital admission, and a yea r of treatment with carvedilol resulted in the avoidance of one such s erious event among every 12-13 (SE 5) of these patients with chronic s table heart failure.