Nearly all patients who have an acute myocardial infarction will be started on a β-blocker (usually either atenolol or metoprolol) within 48 hours of the event. It is important to determine whether the patient has a preserved ejection fraction after the MI. If they have significant LV dysfunction with reduced ejection fraction, β-blockers could cause decompensated heart failure.

Evidence currently supports continuing the β-blocker for at least 3 years.

Why do we give a β-blocker after an MI?

β-blockers significantly reduce mortality in patients post-myocardial infarction (see ISIS-1 trial).

Multiple mechanisms have been proposed for this observation:

• Negative inotropy and chronotropy reduces myocardial oxygen demand, and improves ventricular filling in diastole, which is beneficial to ischaemic myocardium.
• Negative chronotropy and anti-arrhythmic effect of β-blockers reduces incidence of potentially fatal tachyarrhythmias (e.g. ventricular fibrillation) associated post-MI.
• Reduced sympathetic activation slows the rate of deleterious cardiac remodelling that occurs post-MI.

β-blockers significantly reduce mortality, morbidity and improve symptoms in patients with chronic heart failure (see CIBIS-II and COMET trials).

They are thought to work in a similar way as in post-myocardial infarction (described above).

Which agent should be used in HF?

Carvedilol, bisoprolol, nebivolol or slow-release metoprolol are preferred in the management of heart failure, as these drugs have been most effective in reducing mortality in clinical trials. Carvedilol is preferred in patients with concomitant HTN due to its additional vasodilating effects, and should be avoided in patients with low blood pressure for the same reason. Nebivolol is reserved for mild-moderate HF.

Tips for starting therapy

Patients should be started at low-doses (e.g. 1.25mg OD bisoprolol) and the dose doubled at regular intervals until a target dose is reached (e.g. 5-10mg OD bisoprolol). The reason for this is to prevent decompensated heart failure. Daily weights should be measured to ensure the patient has no evidence of increasing fluid overload as a result of β-blocker therapy and the patient should be advised to report any symptoms (e.g. SOB, leg swelling). Symptoms may get worse in the first few days of starting β-blocker therapy.

β-blockers now come in at Step 4 of NICE's treatment steps for the management of hypertension and so they are rarely employed as a monotherapy for HTN, but instead are used in combination with vasodilators (ACEi/ARBs, CCBs) and diuretics.

Why do we give β-blockers in hypertension?

When given long-term, β-blockers will lower blood pressure through β1 receptor blockade:

• Blocking β1 in the heart reduces contractility and ultimately this reduces systolic arterial pressure.
• Blocking β1 in the kidneys reduces renin secretion and subsequent release of aldosterone (via the renin-angiotensin-aldosterone system). This chronically reduces intravascular fluid volume, and ultimately reduces diastolic blood pressure.

Acutely, β-blockers can actually cause a rise in blood pressure due to blockade of vasodilating β2 receptors.

β-blockers do not usually cause hypotension in healthy individuals with normal blood pressure.

3rd generation β-blockers (e.g. carvedilol, nebivolol, labetolol) are direct vasodilators through other mechanisms. These β-blockers also have less metabolic side-effects than other β-blockers (e.g. hyperglycaemia and hyperlipidaemia) so these may the be an effective choice in essential HTN (see ESC article).

Migraine

Propanolol is essential in the drug management for the prevention of migraine. After 12 weeks at an adequate dose, it reduces the frequency of attacks by ≥50% in 35-60% of patients. The mechanism is uncertain, however it may be due to cerebral artery vasoconstriction (due to β2 blockade) leading to reduced intracranial pressure.

Tremor

In the same way that β-agonists (e.g. salbutamol) can cause tremor as a side-effect, β-antagonists reduces the amplitude of resting tremor. Propanolol improves symptoms in up to 60% of patients with benign essential tremor. Interestingly, β-blockers are drugs of abuse for sportspersons who want to improve their fine motor control by reducing their natural resting tremor (and so the International Olympic Committee bans β-blockers in archery, billiards, golf and shooting!)

Anxiety

The physical manifestations of anxiety (palpitations, sweating and tremor) are a result of increased sympathetic activation. Propanolol can reduce these physical symptoms, but has no benefit on psychological symptoms.

Why give β-blockers in patients who are hyperthyroid?

Many of the hyperadrenergic symptoms that patients experience in hyperthyroidism (e.g. palpitations, sweating, tremor) can be alleviated with β-blockers. It is also thought that some β-blockers (e.g. propanolol) reduce the conversion of T4 to T3 (NOTE: the action of T3 is responsible for the hyperadrenergic response).

When to give it

Patients who are symptomatically hyperthyroid and are awaiting treatment (e.g. waiting to be started on carbimazole, radioiodine therapy or thyroidectomy) can be started on a cardioselective β-blocker (e.g. atenolol) with the aim of reducing symptoms. A good target is to increase the dose until heart rate <90bpm if tolerated.