Beta-Blocker Cardioselectivity Ranking
Bisoprolol and nebivolol demonstrate the highest degree of β1-selectivity among the beta-blockers listed, with nebivolol having a greater degree of selectivity for β1-adrenergic receptors than other agents in this class, followed by bisoprolol and metoprolol succinate, while carvedilol is non-cardioselective as it blocks β1, β2, and α1 receptors. 1, 2, 3
Cardioselectivity Profile by Agent
Nebivolol (Most Cardioselective)
- Nebivolol exhibits the highest β1-selectivity among currently available beta-blockers, particularly at doses ≤10 mg in extensive metabolizers (most of the population). 2, 3
- At clinically relevant doses, nebivolol does not demonstrate α1-adrenergic receptor blockade activity, maintaining pure β1-selectivity. 2
- The β1-selectivity is so pronounced that at doses <10 mg, nebivolol does not inhibit the normal exercise-induced increase in heart rate, unlike traditional beta-blockers. 3
- In poor metabolizers and at higher doses, nebivolol inhibits both β1 and β2 receptors, but this represents a minority of patients. 2
Bisoprolol (Highly Cardioselective)
- Bisoprolol is classified as a β1-selective (cardioselective) adrenoceptor blocking agent without significant membrane stabilizing activity or intrinsic sympathomimetic activity. 4
- Cardioselectivity is not absolute—at higher doses (≥20 mg), bisoprolol also inhibits β2-adrenoceptors located in bronchial and vascular musculature. 4
- The American College of Cardiology guidelines list bisoprolol among cardioselective beta-blockers and note it is preferred in patients with HFrEF. 1
Metoprolol Succinate (Moderately Cardioselective)
- Metoprolol is a β1-selective (cardioselective) adrenergic receptor blocker, though this preferential effect is not absolute. 5
- At higher plasma concentrations, metoprolol also inhibits β2-adrenoreceptors, chiefly located in bronchial and vascular musculature. 5
- The American Heart Association guidelines recommend short-acting cardioselective β1-selective beta-blockers such as metoprolol or bisoprolol without intrinsic sympathomimetic activity for acute coronary syndromes. 1
Carvedilol (Non-Cardioselective)
- Carvedilol is a combined alpha- and beta-receptor blocker that blocks β1, β2, and α1 adrenergic receptors, making it non-cardioselective. 1
- The α1-blockade provides more potent BP-lowering effects than β1-selective agents, which may be advantageous in patients with ACS and severe hypertension. 1
- Carvedilol should be avoided in patients with obstructive airways disease because of the effects of β2 antagonism on airway resistance. 1
Clinical Implications of Cardioselectivity
Respiratory Safety
- Cardioselective beta-blockers (nebivolol, bisoprolol, metoprolol) are preferred in patients with bronchospastic airway disease requiring a beta-blocker. 1
- Several meta-analyses concluded that cardioselective β-blockers do not produce clinically significant adverse respiratory effects in patients with chronic obstructive pulmonary disease. 1
Metabolic Effects
- The European Society of Cardiology recommends nebivolol for superior metabolic effects compared to atenolol and metoprolol, particularly in patients with metabolic syndrome or diabetes risk. 1, 6
- Nebivolol does not worsen glucose tolerance even when combined with hydrochlorothiazide, whereas traditional beta-blockers increase diabetes risk. 1
Important Caveats
- Cardioselectivity is dose-dependent and not absolute for any agent—all β1-selective blockers will inhibit β2 receptors at sufficiently high doses. 2, 5, 4
- While nebivolol has the highest β1-selectivity, for heart failure with reduced ejection fraction, the American Heart Association notes that the strongest mortality reduction evidence supports bisoprolol, carvedilol, and metoprolol succinate. 7, 6
- The clinical significance of differences in cardioselectivity between nebivolol, bisoprolol, and metoprolol may be modest in most patients, but becomes more relevant in those with reactive airways disease or metabolic concerns. 1, 3