Cardioselective Beta-Blockers
The cardioselective (β1-selective) beta-blockers are nebivolol, bisoprolol, metoprolol (both tartrate and succinate formulations), and atenolol, with nebivolol and bisoprolol demonstrating the highest degree of β1-selectivity. 1
Ranked by Cardioselectivity
The American College of Cardiology establishes the following hierarchy of β1-selectivity 1:
- Nebivolol - highest β1-selectivity, with additional nitric oxide-mediated vasodilation 2
- Bisoprolol - second highest β1-selectivity 1
- Metoprolol succinate (extended-release) - moderate β1-selectivity 1
- Metoprolol tartrate (immediate-release) - moderate β1-selectivity 1
- Atenolol - moderate β1-selectivity 3
Non-Cardioselective Agent for Comparison
Carvedilol is NOT cardioselective - it blocks β1, β2, and α1 adrenergic receptors, making it a combined alpha- and beta-receptor blocker 1
Clinical Implications of Cardioselectivity
Respiratory Safety
Cardioselective beta-blockers (nebivolol, bisoprolol, metoprolol) are preferred in patients with bronchospastic airway disease requiring beta-blocker therapy, as multiple meta-analyses concluded they 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. Nebivolol does not worsen glucose tolerance even when combined with hydrochlorothiazide, whereas traditional beta-blockers increase diabetes risk 1
Evidence-Based Recommendations by Condition
Heart Failure with Reduced Ejection Fraction
The American Heart Association and American College of Cardiology note that the strongest evidence for mortality reduction in HFrEF supports bisoprolol, carvedilol, and sustained-release metoprolol succinate 2. Nebivolol demonstrated mortality reduction particularly in elderly patients (≥70 years) in the SENIORS trial 2
Acute Coronary Syndromes
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
Hypertension
For hypertension management, all cardioselective agents are effective, though nebivolol offers metabolic advantages 1. The α1-blockade in carvedilol (non-selective) provides more potent BP-lowering effects than β1-selective agents, which may be advantageous in patients with ACS and severe hypertension 1
Critical Warnings for All Beta-Blockers
Abrupt Discontinuation
Do not abruptly discontinue any beta-blocker in patients with coronary artery disease - severe exacerbation of angina, myocardial infarction, and ventricular arrhythmias have been reported 4, 5. Taper over 1-2 weeks when discontinuing 4, 5
Bronchospastic Disease
While cardioselective agents are safer, the FDA warns that patients with bronchospastic disease should generally not receive beta-blockers 4, 5. If necessary, use the lowest possible dose and ensure bronchodilators are readily available 4
Diabetes and Hypoglycemia
Beta-blockers may mask tachycardia occurring with hypoglycemia, though other manifestations like dizziness and sweating may not be significantly affected 4, 5