Is nebivolol (beta blocker) useful in coronary artery disease (CAD) and heart failure?

Nebivolol in Coronary Artery Disease and Heart Failure

Nebivolol is effective for patients with coronary artery disease (CAD) and heart failure with reduced ejection fraction (HFrEF), offering benefits in both symptom control and cardiovascular outcomes. 1

Efficacy in Heart Failure

Heart Failure with Reduced Ejection Fraction (HFrEF)

• Nebivolol is recognized as a beta-blocker that can reduce mortality in heart failure patients, particularly in elderly populations (≥70 years) as demonstrated in the SENIORS trial 2
• However, it is not among the three beta-blockers with the strongest evidence for mortality reduction in HFrEF, which are bisoprolol, carvedilol, and sustained-release metoprolol succinate 1
• Nebivolol demonstrated a modest reduction in the primary endpoint of all-cause mortality or cardiovascular hospitalization in elderly heart failure patients, though it did not affect mortality alone when patients with preserved ejection fraction were included 1

Heart Failure with Preserved Ejection Fraction (HFpEF)

• The European Society of Cardiology guidelines suggest nebivolol may be considered for decreasing hospitalization in HFpEF patients 1
• The SENIORS trial investigated nebivolol versus placebo in unselected heart failure patients without low ejection fraction as a selection criterion, with positive results for the primary endpoint (composite of hospitalization for heart failure and death) 1
• In a prespecified subgroup analysis, there was no difference in outcome between patients with reduced compared to preserved ejection fraction 1

Benefits in Coronary Artery Disease

• Nebivolol reduces cardiac ischemic events in patients with heart failure of ischemic etiology by approximately one-third compared to placebo (HR 0.68; 95% CI 0.51 to 0.90) 3
• It significantly improves coronary flow reserve (CFR) in patients with idiopathic dilated cardiomyopathy after one month of treatment (2.02 ± 0.35 vs 2.61 ± 0.43, p<0.001) 4
• Intracoronary nebivolol increases CFR in both healthy controls and CAD patients, though through different mechanisms (reduction in resting flow in controls, increase in maximal coronary flow in CAD patients) 5

Unique Pharmacological Properties

• Nebivolol is a highly selective beta-1 adrenergic receptor blocker with vasodilating properties 2, 6
• Its vasodilatory effects are mediated through the endothelial L-arginine/nitric oxide pathway, which may contribute to its clinical profile in both heart failure and CAD 2, 6
• This nitric oxide-mediated vasodilation differentiates nebivolol from other beta-blockers and may provide additional benefits in patients with endothelial dysfunction 2, 5

Clinical Application and Dosing

• For heart failure patients, nebivolol should be initiated at low doses (2.5 mg daily) and titrated gradually 6
• In CAD patients, abrupt discontinuation should be avoided as it may lead to severe exacerbation of angina, myocardial infarction, and ventricular arrhythmias 7
• When used for antianginal purposes in CCS (chronic coronary syndromes), the aim should be to lower resting heart rate to 55-60 beats per minute 1

Cautions and Contraindications

• Nebivolol should not be abruptly discontinued in patients with CAD due to risk of severe exacerbation of angina, myocardial infarction, and ventricular arrhythmias 7
• The FDA notes that nebivolol was not specifically studied in patients with angina pectoris or recent myocardial infarction 7
• In elderly heart failure patients (>70 years), a maximum dose of 10 mg per day has been studied with no worsening of heart failure compared to placebo 7
• Special caution is needed in patients with bronchospastic diseases, during anesthesia and major surgery, and in those at risk for hypoglycemia 7

Comparison with Other Beta-Blockers

• While nebivolol shows benefits in CAD and heart failure, the strongest evidence for mortality reduction in HFrEF supports bisoprolol, carvedilol, and sustained-release metoprolol succinate 1
• In patients with CAD and left ventricular dysfunction, one study suggested that ivabradine with standard therapy provided better anti-ischemic effects and improved heart failure symptoms compared to nebivolol 8
• Nebivolol's unique nitric oxide-mediated vasodilation may provide additional benefits beyond traditional beta-blockade, particularly in patients with endothelial dysfunction 2, 5