Nonselective Versus Selective β-Adrenergic Receptor Blockade in Congestive Heart Failure

Abstract

Background-Activation of the sympathetic nervous system has important prognostic implications in chronic heart failure.Nonselective versus selective ␤-adrenergic receptor antagonists may have differential effects on norepinephrine release from nerve terminals mediated by prejunctional ␤ 2 -adrenergic receptors. Methods and Results-Thirty-six patients with chronic heart failure were randomized to the nonselective ␤-blocker carvedilol or the selective ␤-blocker metoprolol (double-blind). Measurements of hemodynamics and cardiac and systemic norepinephrine spillover as well as microneurographic recordings of muscle sympathetic nerve traffic were made before and after 4 months of therapy. In the carvedilol group (nϭ17), there were significant reductions in both total body (Ϫ1.7Ϯ0.5 nmol/min, PϽ0.01) and cardiac norepinephrine spillover (Ϫ87Ϯ29 pmol/min, PϽ0.01). By contrast, in the metoprolol group (nϭ14), there were no significant changes in total body or cardiac norepinephrine spillover. Responses in the carvedilol group were significantly different from those observed in the metoprolol group (PϽ0.05). Both agents caused a reduction in heart rate and increases in pulse pressure, although mean arterial pressure did not change. Importantly, microneurographic measures of sympathetic nerve traffic to skeletal muscle did not change in either group. Conclusions-Therapy with carvedilol caused significant decreases in systemic and cardiac norepinephrine spillover, an indirect measure of norepinephrine release. Such changes were not observed in patients treated with metoprolol. There was no effect of either agent on sympathetic efferent neuronal discharge to skeletal muscle. These findings suggest that carvedilol, a nonselective ␤-blocker, caused its sympathoinhibitory effect by blocking peripheral, prejunctional ␤-adrenergic receptors. (Circulation. 2001;104:2194-2199.)

Sympathetic Drive in Anterior and Inferior Uncomplicated Acute Myocardial Infarction

“…4 With regard to therapy, it has been reported in patients with heart failure that ACE inhibitors decrease sympathetic nerve activity 35 and that ␤-blockers have no effect on MSNA. 36 Values of s-MSNA (top) and MSNA (bottom) in 17 patients with ant-AMI, 22 patients with inf-AMI, and corresponding values obtained in 20 matched normal subjects (NC). Height of column indicates mean value of group, and bars, SEM.…”

Treatment of Chronic Heart Failure With β-Adrenergic Receptor Antagonists

“…Carvedilol does not reduce systemic adrenergic drive compared with placebo in patients with heart failure, although it results in lower NE levels than metoprolol. 90 In some studies in heart failure, measurements of coronary sinus NE 90 or cardiac spillover 114 have demonstrated that carvedilol lowers cardiac adrenergic drive compared with placebo 90 or metoprolol. 114 However, another study 115 has not detected a difference in reduction of cardiac adrenergic drive between carvedilol and placebo or metoprolol.…”

“…90 In some studies in heart failure, measurements of coronary sinus NE 90 or cardiac spillover 114 have demonstrated that carvedilol lowers cardiac adrenergic drive compared with placebo 90 or metoprolol. 114 However, another study 115 has not detected a difference in reduction of cardiac adrenergic drive between carvedilol and placebo or metoprolol. The sympatholytic effects of bucindolol and to a much lesser degree carvedilol add to these compounds' antiadrenergic profiles, and in the case of bucindolol must be considered in the therapeutic targeting of the drug.…”

Which Beta-Blocker is Most Effective in Heart Failure?

“…In heart failure patients carvedilol exerts a more potent anti-adrenergic effect than metoprolol during stress [34,35] (Fig. 2).…”