Carvedilol: CARVEDILOL IN CHF(6)

The two largest trials evaluating the use of beta-blockers in heart failure were the Multicenter Dilated Cardiomyopathy Trial (MDC) and the Cardiac Insufficiency Bisoprolol Study (CIBIS) (Table 1). Neither of these trials was able to demonstrate a survival benefit with the use of beta-blockers. The MDC trial , which comprised patients with heart failure secondary to IDCM only, demonstrated no difference in mortality with the administration of metoprolol compared with that ofplacebo. buy ampicillin

However, there was a significant reduction in the need for cardiac transplantation (defined by deterioration in hemodynamic parameters, progression of heart failure symptoms, and continuous or repeated hospitalizations for heart failure) in patients who were receiving beta-blocker therapy. The CIBIS trial , which comprised patients with heart failure of both IDCM and ischemic origin, randomly assigned patients to bisoprolol (a cardioselectve beta-blocker) or placebo. In patients receiving bisoprolol, there was a reduction in hospitalizations due to CHF, CHF-related events and ventricular arrhythmias, as well as an improvement in NYHA class. A reduction in mortality, however, was seen only in patients with heart failure secondary to IDCM.

TABLE 1 Randomized, controlled mortality trials of beta-blockers in heart failure

Study (reference) Drug and mean dose Samplesize Types of patients (cause of CHF) Mean duration of follow-up Other therapy (% of patients) Efficacy Adverse effects
Anderson et al Metoprolol 61 mg/day* 50 –    Idiopathic dilatedcardiomyopathy only–    Mean ejection fraction28%–    Mean NYHA class 2.8 19 months (range 1 to 38) –    Digitalis–    Diuretics -Vasodilators–    Oral anticoagulants (percentages not specified) –    No difference in mortality–    Improvements in functional assessment –    Three early dropouts due to decreased cardiac output–    Two late dropouts due to increased CHF
Waagstein et al Metoprolol 108 mg/day* 383 –    Idiopathic dilatedcardiomyopathy only–    Mean ejection fraction22%-94% NYHA class II or III 12 to 18 months –    Diuretics (76%) -ACEI (80%)–    Digitalis (78%)–    Nitrates (14%) –    No difference in mortality–    Significant decrease in need for transplant (risk reduction 34%, P<0.0001)–    Significant increase in ejection fraction, exercise capacity and NYHA class – 21 patients withdrawn due to increased CHF during titration and trial period (no difference between metoprolol and placebo)
CIBIS Bisoprolol 3.8 mg/day (no open-label phase) 641 –    Idiopathic dilatedcardiomyopathy, ischemia, hypertension, valvular heart disease–    Mean ejection fraction25.4%-95% NYHA class III 1.9 years –    Diuretics (100%) -ACEI (90%)–    Digitalis (56%)–    Other vasodilators(40%) –    No difference in mortality–    Significant decrease in heart failure–    Significant increase in NYHA class–    Survival benefit in patients with idiopathic dilated cardiomyopathy –    Similar study withdrawal rates–    Four patients on bisoprolol withdrawn due to bradycardia or atrioventricular block
US Carvedilol Heart Failure Study Group Carvedilol 45 mg/day* 1094* –    Idiopathic dilatedcardiomyopathy and ischemia–    Mean ejection fraction22.5%-97% NYHA class II or III 6.5 months* –    Diuretics (95%) -ACEI (95%)–    Digitalis (90%)–    Other vasodilators(32%) –    Significant decrease in mortality from 7.8% to 3.2% (65% risk reduction [Cl 39% to 89%], P<0.001)–    Significant decrease in hospitalizations due to CHF – 11 % of patients on carvedilol withdrawn due to increased CHF during titration and trial period

*Open-labelphase followed by dosage titration up to maximally tolerated doses;f Stratified into four groups based on exercise capacity; *Trial terminated early due to beneficial effects. ACEI Angiotensin-converting enzyme inhibitors; CHF Congestive heart failure; CIBIS Cardiac Insufficiency Bisoprolol Study; NYHA New York Heart Association; US United States

This entry was posted in Carvedilol and tagged Beta-blocker, Carvedilol, Congestive heart failure.