Emiliano Boldi

Differential Effects of β-Blockers in Patients With Heart Failure: A Prospective, Randomized, Double-Blind Comparison of the Long-Term Effects of Metoprolol Versus Carvedilol

BACKGROUND Both metoprolol and carvedilol produce hemodynamic and clinical benefits in patients with chronic heart failure; carvedilol exerts greater antiadrenergic effects than metoprolol, but it is unknown whether this pharmacological difference results in hemodynamic and clinical differences between the 2 drugs. METHODS AND RESULTS We randomized 150 patients with heart failure (left ventricular ejection fraction </=0.35) to double-blind treatment with either metoprolol or carvedilol. When compared with metoprolol (124+/-55 mg/d), patients treated with carvedilol (49+/-18 mg/d) showed larger increases in left ventricular ejection fraction at rest (+10.9+/-11.0 versus +7.2+/-7.7 U, P=0.038) and in left ventricular stroke volume and stroke work during exercise (both P<0. 05) after 13 to 15 months of treatment. In addition, carvedilol produced greater decreases in mean pulmonary artery pressure and pulmonary wedge pressure, both at rest and during exercise, than metoprolol (all P<0.05). In contrast, the metoprolol group showed greater increases in maximal exercise capacity than the carvedilol group (P=0.035), but the 2 drugs improved symptoms, submaximal exercise tolerance, and quality of life to a similar degree. After a mean of 23+/-11 months of follow-up, 21 patients in the metoprolol group and 17 patients in the carvedilol group died or underwent urgent transplantation. CONCLUSIONS The present study demonstrates that during long-term therapy, carvedilol improves cardiac performance to a greater extent than metoprolol when administered to patients with heart failure in the doses shown to be effective in clinical trials. These differences were likely related to a greater antiadrenergic activity of carvedilol.

Differential Effects of β-Blockers in Patients With Heart Failure

Background—Both metoprolol and carvedilol produce hemodynamic and clinical benefits in patients with chronic heart failure; carvedilol exerts greater antiadrenergic effects than metoprolol, but it is unknown whether this pharmacological difference results in hemodynamic and clinical differences between the 2 drugs. Methods and Results—We randomized 150 patients with heart failure (left ventricular ejection fraction ≤0.35) to double-blind treatment with either metoprolol or carvedilol. When compared with metoprolol (124±55 mg/d), patients treated with carvedilol (49±18 mg/d) showed larger increases in left ventricular ejection fraction at rest (+10.9±11.0 versus +7.2±7.7 U, P=0.038) and in left ventricular stroke volume and stroke work during exercise (both P<0.05) after 13 to 15 months of treatment. In addition, carvedilol produced greater decreases in mean pulmonary artery pressure and pulmonary wedge pressure, both at rest and during exercise, than metoprolol (all P<0.05). In contrast, the metoprolol gr...

A rationale for the use of β-blockers as standard treatment for heart failure☆

Abstract Background Cardiac sympathetic activation is one of the major and earlier changes observed in patients with heart failure. Its relation to the severity of the disease and its independent prognostic value show that it may directly contribute to the progression of heart failure. β-Blockers are the most effective tool to counteract the untoward effects of sympathetic activation on the cardiovascular system. Methods and Results We reviewed the results of the placebo-controlled, double-blind studies about the effects of β-blockers in patients with heart failure. These studies have involved almost 10,000 patients to date and have consistently shown that the long-term administration of β-blockers is associated with a highly significant improvement in both left ventricular function and prognosis of the patients with heart failure. The evidence supporting the use of ν-blockers now equals or even surpasses that of angiotensin-converting enzyme inhibitors; therefore β-blockers should be considered part of standard therapy. Issues that remain unclarified include the mechanisms through which β-blockers may improve cardiac function and their tolerability and efficacy in specific groups of patients (such as those with asymptomatic left ventricular dysfunction, severe heart failure, the elderly, or those with left ventricular diastolic dysfunction). It is not currently clear whether the pharmacologic differences between indvidual β-blockers are clinically relevant. If they are, the potential for even greater benefit with certain agents exists. It is hoped that these issues will be clarified by the results of ongoing multicenter trials.

Maximal and submaximal exercise testing in heart failure.

Although reduced exercise capacity is the main complaint of patients with congestive heart failure (CHF), the best method to measure it remains controversial. Peak VO2, obtained using maximal exercise testing, is the most accurate measure of maximal functional capacity. It is related to peak exercise cardiac output and is one of the most important independent variables for the prognostic assessment of patients with CHF. It has, however, a low sensitivity for measurement of changes induced by therapy and is poorly related to everyday physical activity, patient symptoms, and quality of life. The anerobic threshold may also be regarded as a parameter of maximal functional capacity. Its value is mainly indirect, because it shows that the patient is performing a maximal effort limited by the cardiovascular system. The VO2 kinetics at the start and at the end of exercise are probably more related to patient symptoms, but it is unresolved which protocols and parameters might best be used to study this aspect of exercise performance. Duration of a submaximal exercise at a constant work rate and the distance walked during a 6-min walking test are gaining wide popularity as parameters of submaximal performance. However, when these exams are carried out up to exhaustion in patients with severe functional limitation, they may involve attainment of the anerobic threshold and therefore their clinical meaning may be similar to the one of a maximal exercise test. Moreover, tests based on the assessment of submaximal exercise capacity have been useful for assessment of therapy in single-center trials but have been often inadequate in multicenter trials.