Beta-blockers Topic Review

Beta-blockers antagonize beta-1 and beta-2 receptors which are the usual targets of the sympathetic nervous system, including epinephrine and norepinephrine.

This results in a decreased heart rate through decreased sinoatrial (SA) node activity and decreased atrioventricular (AV) nodal conduction, as well as decreased inotropy — contractility — of the heart.

Indications

Beta-blockers are used to treat hypertension (but are not recommended as first-line therapy unless the patient has ischemic heart disease or heart failure [HF]) [Whelton PK, et al. Hypertension. 2017;1289a], tachyarrhythmias such as atrial fibrillation (AF) and systolic congestive HF [Heidenreich PA, et al. J Am Coll Cardiol. 2022;e295; Al-Khatib SA, et al. J Am Coll Cardiol. 2017;e116]. Other less common indications include anxiety, migraine headache prophylaxis and stage fright.

Examples of Beta-blockers

Some examples of beta-blockers include:

• atenolol;
• acebutolol;
• betaxolol;
• bisoprolol;
• carteolol;
• carvedilol;
• esmolol;
• labetalol;
• metoprolol;
• nadolol;
• penbutolol;
• pindolol;
• propranolol;
• sotalol; and
• timolol.

Common Reactions

Common reactions to beta-blocker therapy may include:

• bradycardia;
• hypotension;
• exacerbation of systolic HF;
• dizziness;
• erectile dysfunction; and
• fatigue.

Properties

The four different properties of beta-blockers are:

• cardioselectivity;
• lipid solubility;
• intrinsic sympathomimetic activity; and
• membrane stabilization.

Each beta-blocker has a different amount of these properties and it is important to consider these when selecting a beta-blocker for a specific condition. The Table below summarizes which beta-blockers possess each property.

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Cardioselectivity: All beta-blockers act upon both beta-1 and beta-2 receptors. The “cardioselective” beta-blockers act upon beta-1 receptors much more than the beta-2 receptors. For this reason, the cardioselective beta-blockers are safer to use in patients with asthma or reactive airway diseases.

Lipid solubility: Beta-blockers that are lipid soluble, such as propranolol or metoprolol, can cross the blood-brain barrier easily. These medications are commonly used for migraine headaches, stage fright and panic attacks for these reasons.

Intrinsic sympathomimetic activity (ISA): Beta-blockers with ISA only partially antagonize while actually causing a small degree of activation of the beta receptors. Therefore, they will have some beta-blocking effects, but not to the degree of beta-blockers without ISA. These are commonly used in younger patients or in athletes where heart rates need to elevate, allowing overall increased cardiopulmonary effort, in order to compete in sports. Examples include pindolol and acebutolol.

Membrane stabilization: Stabilizing membranes decreases the propagation of action potentials. This is also the mechanism that local anesthetics work (lidocaine). Class I antiarrhythmic drugs possess this characteristic as well. The importance of this is not clear in clinical medicine with regard to beta-blockers. Perhaps this is partially an explanation for propranolol treating migraine headaches.

Additional Information

Beta-blockers should be initiated in patients hospitalized with acute systolic congestive HF prior to hospital discharge. It is reasonable to withhold beta-blockers in patients who were previously taking them in the outpatient setting for chronic systolic HF when they are admitted with HF exacerbation.

Beta-blockers are contraindicated specifically in systolic HFwhen pulmonary edema is present, when there are signs of cardiogenic shock, severe bradycardia, hypotension or wheezing related to asthma.

Beta-blockers are contraindicated during an acute myocardial infarction (MI) when there are signs of pending cardiogenic shock. These include systolic blood pressure below 110 mm Hg and pulmonary edema. Typical contraindications include severe bradycardia, heart block more advanced than first degree (unless a pacemaker is in place) and for use during a MI from cocaine use.

Esmolol has a very short half-life and is used as a continuous intravenous (IV) drip.

Beta-blocker overdose can be life-threatening. The treatment is glucagon and dobutamine/milrinone.

Beta-blockers cause insulin resistance, decrease high-density lipoprotein (HDL) cholesterol levels and increase triglyceride levels.

Beta-blockers mask the symptoms of hypoglycemia in patients with diabetes, which is predominantly mediated through the sympathetic nervous system (sweating, tachycardia).

Guideline Recommendations: Heart Failure

Beta-blockers are recommended (Class 1 recommendation) to reduce mortality in patients with HF with reduced ejection fraction (HFrEF; ≤ 40%) and a recent or remote history of MI or acute coronary syndrome (ACS) and to prevent symptomatic HF in patients with EF of 40% or less. [Heidenreich PA, et al. J Am Coll Cardiol. 2022;e295]

To reduce mortality and hospitalizations in patients with HFrEF and current or previous symptoms, the preferred beta-blockers are bisoprolol, carvedilol and sustained-release metoprolol succinate (Class 1 recommendation); in this population, beta-blocker therapy provides high economic value (Class A statement). [Heidenreich PA, et al. J Am Coll Cardiol. 2022;e295]

In patients with HF with midrange EF (41%-49%) with current or previous HF symptoms, beta-blockers may be considered (Class 2b recommendation) for reduction of HF hospitalization and CV mortality, particularly in those at the lower end of the EF spectrum. [Heidenreich PA, et al. J Am Coll Cardiol. 2022;e326]

Use of beta-blockers is reasonable (Class 2a recommendation) to prevent progression to HF and to improve cardiac function in asymptomatic patients with cancer therapy-related cardiomyopathy. [Heidenreich PA, et al. J Am Coll Cardiol. 2022;e358]

In patients at risk for cancer therapy-related cardiomyopathy, use of beta-blockers for primary prevention is of uncertain benefit (Class 2b recommendation). [Heidenreich PA, et al. J Am Coll Cardiol. 2022;e358]

Guideline Recommendations: Arrhythmias

Beta-blockers have a Class 2a recommendation for treatment of symptomatic ventricular arrhythmias that are not life-threatening. [Al-Khatib SA, et al. J Am Coll Cardiol. 2017;e118] 

IV beta-blockers can be useful (Class 2a recommendation) in patients with polymorphic ventricular tachycardia (VT) due to myocardial ischemia and in those with a recent MI and VT/ventricular fibrillation (VF) that reoccurs despite electrical cardioversion and use of antiarrhythmic drugs. [Al-Khatib SA, et al. J Am Coll Cardiol. 2017;e119-e120]

Beta-blockers are recommended (Class I recommendation) in patients with arrhythmogenic right ventricular cardiomyopathy and ventricular arrhythmias and may be useful (Class 2a recommendation) in those with arrhythmogenic right ventricular cardiomyopathy but not ventricular arrhythmias. [Al-Khatib SA, et al. J Am Coll Cardiol. 2017;e136]

Beta-blockers are recommended (Class I recommendation) in patients with long QT syndrome with a resting QTc > 470 ms and are reasonable to use (Class 2a recommendation) in asymptomatic patients with long QT syndrome with a resting QTc < 470 ms. [Al-Khatib SA, et al. J Am Coll Cardiol. 2017;e150-e151] In mothers with long QT syndrome, beta-blockers should be continued (Class I recommendation) throughout pregnancy and the postpartum period. [Al-Khatib SA, et al. J Am Coll Cardiol. 2017;e166] 

Beta-blockers are recommended (Class I recommendation) in patients with catecholaminergic polymorphic VT. [Al-Khatib SA, et al. J Am Coll Cardiol. 2017;e155]

Beta-blockers are useful (Class I recommendation) to reduce recurrent arrhythmias and improve symptoms in patients with symptomatic premature ventricular contractions in an otherwise normal heart. [Al-Khatib SA, et al. J Am Coll Cardiol. 2017;e160]

Beta-blockers are useful (Class I recommendation) in patients with symptomatic outflow tract VT in an otherwise normal heart. [Al-Khatib SA, et al. J Am Coll Cardiol. 2017;e161] 

Beta-blocker use is reasonable (Class 2a recommendation) to reduce recurrent arrhythmias and improve symptoms and LV function in patients with premature ventricular contraction-induced cardiomyopathy. [Al-Khatib SA, et al. J Am Coll Cardiol. 2017;e164] 

Beta-blockers can be beneficial (Class 2a recommendation) to reduce risk for sudden cardiac arrest in patients with repaired severe-complexity adult congenital heart disease and frequent or complex ventricular arrhythmias. [Al-Khatib SA, et al. J Am Coll Cardiol. 2017;e171] 

Beta-blockers are recommended (Class 1 recommendation) for acute rate control in patients with AF with rapid ventricular response who are hemodynamically stable. [Joglar JA, et al. J Am Coll Cardiol. 2023;67a]

Beta-blockers are recommended (Class 1 recommendation) for long-term rate control in patients with AF; the choice between a beta-blocker and a calcium channel blocker should depend on underlying substrate and comorbid conditions. [Joglar JA, et al. J Am Coll Cardiol. 2023;70a]

In pregnant individuals with persistent AF, beta-blockers such as propranolol or metoprolol are reasonable to use (Class 2a recommendation) as first-line therapy for rate control. [Joglar JA, et al. J Am Coll Cardiol. 2023;120a]

Sotalol should not be used for antiarrhythmic purposes in patients with HF because these patients are likely already taking a beta-blocker. [Joglar JA, et al. J Am Coll Cardiol. 2023;86a]

Beta-blockers are contraindicated (Class 3 recommendation: Harm) in patients with AF with anterograde accessory pathway conduction (preexcited AF) due to risk for precipitating VF or hemodynamic deterioration. [Joglar JA, et al. J Am Coll Cardiol. 2023;111a]

It is reasonable (Class 2a recommendation) to administer short-term prophylactic beta-blockers before cardiac surgery to reduce risk for postoperative AF in patients with high risk. [Joglar JA, et al. J Am Coll Cardiol. 2023;114a]

Beta-blockers are recommended (Class 1 recommendation) to achieve rate control in patients with AF after cardiac surgery. [Joglar JA, et al. J Am Coll Cardiol. 2023;115a] 

In patients with AF and chronic obstructive pulmonary disease, it is reasonable (Class 2a recommendation) to use cardioselective beta-blockers for rate control of AF, especially where other indications such as MI and HF exist. [Joglar JA, et al. J Am Coll Cardiol. 2023;119a]

Guideline Recommendations: Hypertension

Atenolol, betaxolol, bisoprolol and metoprolol are preferred for patients with bronchiospastic airway disease. [Whelton PK, et al. Hypertension. 2017;1289a]

Carvedilol is the preferred antihypertensive agent in patients with HFrEF. [Whelton PK, et al. Hypertension. 2017;1289a] 

Adults with stable ischemic heart disease and hypertension (BP ≥ 130/80 mm Hg) should be treated (Class 1 recommendation) with medications such as beta-blockers, ACE inhibitors and angiotensin receptor blockers for compelling indications (eg, previous MI, stable angina) as first-line therapy, with the addition of other drugs as needed to further control hypertension. [Whelton PK, et al. Hypertension. 2017;1291b]

Beta-blockers may be continued (Class 2a recommendation) as long-term antihypertensive therapy for more than 3 years after an MI or ACS. [Whelton PK, et al. Hypertension. 2017;1291b]

Beta-blockers may be considered (Class 2b recommendation) for control of hypertension in patients with coronary artery disease and an MI (but not HFrEF) more than 3 years prior. [Whelton PK, et al. Hypertension. 2017;1291b]

Beta-blockers are recommended (Class 1 recommendation) for hypertension control in adults with HF with preserved EF (HFpEF) and persistent hypertension after management of volume overload. [Whelton PK, et al. Hypertension. 2017;1292a]

Beta-blockers are the preferred antihypertensive agents (Class 1 recommendation) for patients with hypertension and thoracic aortic disease. [Whelton PK, et al. Hypertension. 2017;1296b]

The beta-blocker labetalol is among the antihypertensive drugs that women with hypertension who are pregnant or are planning to become pregnant may be transitioned to (Class 1 recommendation). [Whelton PK, et al. Hypertension. 2017;1297b]

Guideline Recommendations: Other

Beta-blockers are contraindicated in patients with acute pulmonary edema. [Whelton PK, et al. Hypertension. 2017;1300a]

In patients with ACS, contraindications to beta-blockers include moderate-to-severe LV failure with pulmonary edema, bradycardia, hypotension, poor peripheral perfusion, second- or third-degree heart block and reactive airways disease. [Whelton PK, et al. Hypertension. 2017;1300a]

In patients with hypertension undergoing major surgery who are already treated with a beta-blocker, the beta-blocker should be continued (Class 1 recommendation). [Whelton PK, et al. Hypertension. 2017;1301a]

Beta-blockers should not be started on the day of surgery in patients who have not taken them before (Class 3 recommendation: Harm). [Whelton PK, et al. Hypertension. 2017;1301a]

References:

• Al-Khatib SM, et al. J Am Coll Cardiol. 2017;doi:10.1016/j.jacc.2017.01.054.
• Farzam K, et al. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK532906. Updated Aug. 22, 2023. Accessed May 1, 2024.
• Heidenreich PA, et al. J Am Coll Cardiol. 2022;doi:10.1016/j.jacc.2021.12.012.
• Joglar JA, et al. J Am Coll Cardiol. 2023;doi:10.1016/j.jacc.2023.08.017.
• Whelton PK, et al. Hypertension. 2017;doi:10.1161/HYP.0000000000000066.