Nebivolol improved left ventricular ejection fraction 4 weeks after myocardial infarction compared with metoprolol (32% vs 17%, p<0.05) and improved survival compared with placebo in mice.
RCT (n=90)
randomized
Does nebivolol improve left ventricular dysfunction and remodeling early after myocardial infarction in mice compared to metoprolol or placebo?
In a murine model of myocardial infarction, nebivolol improved left ventricular dysfunction and survival more than conventional beta-1 blockade with metoprolol, likely via nitric oxide-mediated endothelial effects.
Absolute Event Rate: 32% vs 17%
p-value: p=<0.05
OBJECTIVES: The aim of this study was to investigate whether nebivolol has added effects on left ventricular (LV) dysfunction and remodeling early after myocardial infarction (MI) beyond its β₁-receptor-blocking properties. BACKGROUND: Nebivolol is a third-generation selective β₁-adrenoreceptor antagonist that stimulates endothelial cell nitric oxide (NO) production and prevents vascular reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation. Both endothelial NO synthase-derived NO production and NADPH oxidase activation are critical modulators of LV dysfunction early after MI. METHODS: Mice with extensive anterior MI (n = 90) were randomized to treatment with nebivolol (10 mg/kg/day), metoprolol-succinate (20 mg/kg/day), or placebo for 30 days starting on day 1 after surgery. RESULTS: Infarct size was similar among the groups. Both β₁-adrenergic receptor antagonists caused a similar decrease in heart rate. Nebivolol therapy improved endothelium-dependent vasorelaxation and increased early endothelial progenitor cells 4 weeks after MI compared with metoprolol and placebo. Nebivolol, but not metoprolol, inhibited cardiac NADPH oxidase activation after MI, as detected by electron spin resonance spectroscopy analysis. Importantly, nebivolol, but not metoprolol, improved LV dysfunction 4 weeks after MI (LV ejection fraction: nebivolol vs. metoprolol vs. placebo: 32 ± 4% vs. 17 ± 6% vs. 19 ± 4%; nebivolol vs. metoprolol: p < 0.05) and was associated with improved survival 4 weeks post-MI compared with placebo. Nebivolol had a significantly more pronounced inhibitory effect on cardiomyocyte hypertrophy after MI compared with metoprolol. CONCLUSIONS: Nebivolol improves LV dysfunction and survival early after MI likely beyond the effects provided by conventional β₁-receptor blockade. Nebivolol induced effects on NO-mediated endothelial function, early endothelial progenitor cells and inhibition of myocardial NADPH oxidase likely contribute to these beneficial effects of nebivolol early after MI.
Sorrentino et al. (2011) conducted an RCT in Myocardial Infarction (n=90). Nebivolol vs. Metoprolol-succinate (20 mg/kg/day) or placebo was evaluated on Left ventricular ejection fraction (LVEF) 4 weeks after MI (p=<0.05). Nebivolol improved left ventricular ejection fraction 4 weeks after myocardial infarction compared with metoprolol (32% vs 17%, p<0.05) and improved survival compared with placebo in mice.