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, 6, 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, 6
- 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, 6
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 7
- 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 7
- Beta-blockers without intrinsic sympathomimetic activity are preferred in the acute coronary syndrome setting 1, 6