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Beta-blockers

Modes of action & cardiovascular effects, indications, contraindications & side effects

The ESC Prevention of CVD Programme Page on beta-blockers will provide the reader with information regarding the modes of action and cardiovascular effects of beta-blockers, the indications, the contraindications, and the major adverse effects of these drugs. In addition, the typical types and dosages of beta-blockers are summarized.



Modes of action and cardiovascular effects

  • Modes of action: beta-blockers antagonise the effect of beta-adrenergic stimuli [1].
  • Cardiovascular effects: beta-blockers reduce heart rate, cardiac contractility, and systolic blood pressure. They also have anti-arrhythmic effects since they decrease spontaneous firing of ectopic pacemakers, slow conduction, and increase the refractory period of the atrioventricular (AV) node [1].
  • Classification: beta-blockers can be classified as non-selective (combined β1 and β2 blockers) or cardioselective β1-antagonists (see Table 1).

Indications

Acute coronary syndrome

  • Beta-blockers reduce mortality and reinfarction by 20-25% in those who have recovered from an infarction [1].
  • Oral treatment with beta-blockers should be considered for all ST-elevation myocardial infarction (STEMI) patients without contraindications (Class IIa, Level B) [2]. They are indicated if STEMI patients also have heart failure or LV dysfunction (Class I, Level A) [2].

Stable coronary artery disease

  • Beta-blockade is a very effective symptomatic treatment, alone or combined with another drug, for most of patients with classical angina [1].
  • Beta-blockers and/or calcium channel blockers are first-line treatment to control heart rate and anginal symptoms (Class I, Level A) [3].

Heart Failure

  • Beta-blockers have been shown to reduce mortality and heart failure readmissions in patients with heart failure with a reduced ejection fraction (HFrEF) [1].
  • Beta-blockers are recommended, in addition to ACE inhibitors, for patients with stable, symptomatic HFrEF (Class I, Level A) [4].
  • Bisoprolol, Carvedilol, Metoprolol and Nebivolol are licensed for use in HFrEF and should be preferred [4].

Arrhythmia

  • Beta-blockers can be used to slow the heart rate in patients with arrhythmias such as atrial flutter and/or atrial fibrillation [1].
  • They are effective in the control of ventricular arrhythmias related to sympathetic activation, acute coronary syndrome, and heart failure; including the prevention of sudden cardiac death [1].

Contraindications and side effects

  • The most frequent side effects of beta-blockers include: hypotension, bradycardia, bronchospasm, cold extremities, fatigue, headache, sleep disturbances and increased insulin resistance [1].
  • High-degree AV block is an absolute contraindication (if no pacemaker) [1].
  • Use cardioselective beta-blockers in case of chronic obstructive pulmonary disease (COPD); start low and go slow [1].
  • Asthma is a relative contraindication for the use of beta-blockers [4]. These drugs should be used with caution and preferably with specialist advice.

 

Types and typical dosages of the most frequently used beta-blockers [1].

Name Average daily oral dose
Non-selective antagonists
Pindolol 10-40 mg twice a day
Propanolol 40-160 mg twice a day
Sotalol 80-160 mg twice a day
Timolol 5-40 mg twice a day
Carvedilol 25 mg once/twice a day
Selective β1-antagonists
Atenolol 25-100 mg once a day
Bisoprolol 2.5-10 mg once a day
Celiprolol 200-600 mg once a day
Metoprolol 50-200 mg once/twice a day
Nebivolol 2.5-10 mg once a day

 

Practical recommendations for the use of beta-blockers in daily practice [1]

  • Beta-blockers are very effective for the symptomatic treatment of patients with effort angina or arrhythmias.
  • Most evidence for the reduction of cardiovascular events by beta-blockers concerns acute coronary syndrome patients; especially in the presence of LV dysfunction.
  • High-degree AV block (without a pacemaker) is an absolute contraindication.
  • Asthma is a relative contraindication.
  • COPD is a relative contraindication.
  • Start low and go slow with the elderly, COPD, and patients with heart failure.
  • The most frequent side effects include: hypotension, bronchospasm, central effects, and increased insulin resistance.
  • In case of HFrEF: Use evidence-based beta-blockers: carvedilol, bisoprolol, metoprolol, nebivolol.
  • In case of HFrEF: Start low and go slow (up-titration after at least 2 weeks).
  • In case of HFrEF: In case of an episode of exacerbation of heart failure, start after clinical stabilization only.

References


[1] De Sutter J, Mendes M, Franco OH. Chapter 19 Cardioprotective drugs. In: Gielen S, De Backer G, Piepoli MF, Wood D, editors. The ESC Textbook of Preventive Cardiology. 2nd ed. United Kingdom: Oxford University Press, 2016.

[2] Steg G, James SK, Atar D, et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012; 33: 2569–2619.

[3] Montalescot G, Sechtem U, Achenbach S, et al. 2013 ESC guidelines on the management of stable coronary artery disease. Eur Heart J 2013; 34: 2949–3003.

[4] Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Eur Heart J 2016; 37: 2129-2200.

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.

The ESC Prevention of Cardiovascular Disease programme is supported by AMGEN, AstraZeneca, Ferrer, and Sanofi and Regeneron in the form of educational grants.