Which β‑blocker is cardio‑selective (β1‑selective)?

Cardioselective (β1-Selective) Beta-Blockers

The cardioselective β1-selective beta-blockers include metoprolol, atenolol, acebutolol, betaxolol, bisoprolol, and esmolol, with bisoprolol and nebivolol demonstrating the highest degree of β1-selectivity. 1, 2

Complete List of β1-Selective Agents

According to ACC/AHA guidelines, the following beta-blockers demonstrate β1-selectivity (cardioselectivity): 1

• Metoprolol – β1-selective, no partial agonist activity, dosed 50–200 mg twice daily for angina 1
• Atenolol – β1-selective, no partial agonist activity, dosed 50–200 mg per day 1, 3
• Acebutolol – β1-selective with partial agonist activity, dosed 200–600 mg twice daily 1
• Betaxolol – β1-selective, no partial agonist activity, dosed 10–20 mg per day 1
• Bisoprolol – β1-selective, no partial agonist activity, dosed 10 mg per day 1
• Esmolol – β1-selective intravenous agent, no partial agonist activity, dosed 50–300 mcg/kg/min 1

Degree of Cardioselectivity

Bisoprolol and nebivolol exhibit the highest degree of β1-selectivity among available beta-blockers. 2

• Nebivolol demonstrates greater selectivity for β1-adrenergic receptors than other agents in this class, followed by bisoprolol and metoprolol succinate 2
• At therapeutic doses, bisoprolol does not block β2-adrenoceptors to an appreciable extent 4
• Atenolol is β1-selective (cardioselective) without membrane stabilizing or intrinsic sympathomimetic activities, though this preferential effect is not absolute at higher doses 3

Non-Selective Beta-Blockers (for Comparison)

The following agents block both β1 and β2 receptors and are therefore not cardioselective: 1

• Propranolol – non-selective, no partial agonist activity 1, 5
• Nadolol – non-selective, no partial agonist activity 1
• Timolol – non-selective, no partial agonist activity 1, 5
• Labetalol – non-selective combined alpha and beta blocker with partial agonist activity 1
• Pindolol – non-selective with partial agonist activity 1
• Carvedilol – non-selective combined alpha and beta blocker with partial agonist activity 1

Clinical Implications of Cardioselectivity

Cardioselective agents are preferred in patients with bronchospastic airway disease because they cause less bronchospasm than non-selective agents, though bronchospasm can still occur at higher doses. 1, 5

• In asthmatic patients, a dose of atenolol producing a greater effect on resting heart rate than propranolol resulted in much less increase in airway resistance 3
• Cardioselective β-blockers do not produce clinically significant adverse respiratory effects in patients with chronic obstructive pulmonary disease according to multiple meta-analyses 2
• If concerns exist about beta-blocker intolerance, initial selection should favor a short-acting β1-specific drug such as metoprolol or esmolol 1
• Mild wheezing or history of chronic obstructive pulmonary disease mandates a short-acting cardioselective agent at a reduced dose (e.g., 12.5 mg of metoprolol orally) rather than complete avoidance 1

Additional Pharmacologic Distinctions

Cardioselective agents cause less fatigue and result in less hypertension during hypoglycemia than non-selective agents. 5

• Most benefit of β-blockade in hypertension, heart failure, and ischemic heart disease arises from blockade of the β1 receptor 6
• The addition of intrinsic sympathomimetic activity (ISA) appears to reduce the potential for improved clinical outcomes in people with heart failure or ischemic heart disease 6
• Beta-blockers without intrinsic sympathomimetic activity are preferred in the acute coronary syndrome setting 1