Inhibition of adrenergic receptors and therefore of the sympathetic system.

Differences between beta blockers :

• Bisoprolol and metoprolol: selective inhibition of β1 receptors, less of β2 receptors.
• Nebivolol : highly selective inhibition of β1 receptors + NO synthesis (peripheral vasodilation).
• Carvedilol: non-selective inhibition of β1 receptors + α1 receptors (peripheral vasodilation).

• Reduction of sympathetic activity.
• Vasodilation, blood pressure reduction: afterload reduction with increase in cardiac output.
• Slowing down the heart rate:
  • Improved hemodynamics by increasing diastolic filling time and myocardial perfusion time, resulting in higher inotropy, improvement of LVEF and cardiac output.
  • Decrease in myocardial overload and progressive LV dysfunction.
  • Reduction of arrhythmias and sudden death
• Reduction of RAAS activation. Reduction of sodium and water reabsorption in the kidneys: increased sodium excretion and diuresis.
• Myocyte hypertrophy and fibrosis in myocardium.

Trials: CIBIS-II, MERIT-HF, COPERNICUS, COMET, SENIORS, CIBIS III.

Beta-blockers vs. placebo:

• Reduction of all-cause and cardiovascular mortality
• Reduction of hospitalizations for heart failure
• Reduction of symptoms and better quality of life
• Reduction of arrhythmias and sudden death
• Improvement of LVEF

Always consider stable heart failure with LVEF ≤ 40% and strongly consider if LVEF ≤ 50%, unless contraindicated or intolerant.

• Only evidence-based beta blockers should be used as heart failure therapy. These are carvedilol, bisoprolol, nebivolol or metoprolol succinate ( Selozok ). NOT metoprolol tartrate ( Seloken ). Not all beta blockers have shown benefits in past studies in patients with HFrEF .
• The choice of beta blocker is best made by the treating cardiologist.
• Beta blockers should only be started AFTER recompensation (disappearance of signs of fluid retention)!
• Start with a low dose and, if possible, increase the dose in small steps over the course of weeks ( up-titration ): Start low, go slow. See Table.
• Up-titration every 2 weeks (+ 25% of the target dose) if blood pressure ≥ 95 mmHg systolic (without symptoms of hypotension: orthostatism , dizziness, fatigue, malaise) and heart rate ≥ 65/min. The lower the blood pressure or heart rate, the smaller the steps of the up-titration are best (+ 12.5% of the target dose).
• Always try to titrate further to the target dose (see table) or the maximum tolerated dose, as long as blood pressure and heart rate allow this, aiming for a resting heart rate of 55-65/min. Bradycardia < 50/min is best avoided.
• It is best not to up-titrate if there are signs of progressive heart failure or fluid retention.
• A low dose beta -blocker is better than no beta -blocker.
• In the case of terminal heart failure, persistent NYHA IV, the dose may be best reduced in consultation with the treating cardiologist.

• Persistent cardiac decompensation (NYHA IV), restrictive filling pattern (indicating increased LV filling pressure).
• High-grade AV block (2nd or 3rd degree ) (preferably a CRT device, with subsequent starting/increasing beta blocker).
• Heart rate < 50/min (without pacemaker).
• Uncontrolled asthma (NOT COPD).

• If in doubt, it is best to adjust the therapy in consultation with the treating cardiologist.
• Monitoring of blood pressure, heart rate and clinical status (signs of fluid retention?) is necessary.
• When starting or increasing this therapy, blood pressure may be lower and dizziness may occur if you stand up too quickly ( orthostatism ). Due to habituation, these complaints often disappear after a few days and the dose should therefore not be reduced or stopped too quickly.
• In asthma / more severe COPD, preference is given to a highly cardioselective beta blocker (e.g. Nebivolol , Bisoprolol).
• Cardiac decompensation is not a reason to reduce or stop beta blockers, unless there is suspicion of progression to advanced/terminal heart failure (with hypotension and low cardiac output) and/or cardiogenic shock (symptomatic hypotension with oliguria and poorer peripheral perfusion).

If a side effect is suspected, this vital therapy should not simply be stopped. Stopping or switching to another molecule is best done in consultation with the treating cardiologist.

• Cardiovascular:
  • Bradycardia, AV block
  • Hypotension
  • Faster muscle fatigue on exertion, Raynaud's phenomenon , cold extremities (due to reduced muscle perfusion (due to peripheral vasoconstriction due to antagonism β2 receptors). Less with nebivolol and carvedilol.
• Metabolic:
  • Reduction of the symptoms of hypoglycemia (tremor, tachycardia), but still sweating.
  • Possible slight increase in diabetes mellitus (antagonism of β2 receptors causes a slight reduction in insulin secretion). Less use of nebivolol and carvedilol.
• Pulmonary:
  • Bronchoconstriction (asthma >> COPD). Less with nebivolol .
• Central: fatigue, headache, depression, sleep disorders
• Sexual : impotence and reduced libido. Less with nebivolol .
• Itch
• Increased psoriasis
• Hair loss