Role of beta blockers in heart failure

Rationale and mechanism. Chronic heart failure activates the sympathetic nervous system, which is initially compensatory but ultimately causes myocyte toxicity and apoptosis, adverse remodelling, arrhythmia, down-regulation of β -receptors and renin–angiotensin–aldosterone activation. Beta-blockers antagonise this 1 neurohormonal activation, producing reverse remodelling with improved ejection fraction, reduced heart rate with improved diastolic filling and coronary perfusion, reduced myocardial oxygen demand, and antiarrhythmic protection against sudden death.

Evidence and indication. Beta-blockers improve symptoms and survival and are a mainstay of therapy for heart failure due to systolic dysfunction in older as in younger patients. They are indicated in all patients with HFrEF (LVEF ≤ 40%) who are clinically stable and euvolaemic, together with an ACE inhibitor/ARNI, an MRA and an SGLT2 inhibitor. Landmark trials: CIBIS-II (bisoprolol), MERIT-HF (metoprolol succinate), COPERNICUS (carvedilol) and SENIORS (nebivolol, specifically in patients aged ≥ 70), which showed benefit in an elderly population.

Which drugs. Only four agents have proven mortality benefit in heart failure — bisoprolol, carvedilol, metoprolol succinate (extended release) and nebivolol. The benefit is not a class effect: atenolol and short-acting metoprolol tartrate are not substitutes. Carvedilol also has α-blocking and antioxidant activity and is preferred where blood pressure is well maintained; bisoprolol and nebivolol are β -selective and better tolerated in coexisting 1 airways disease; nebivolol additionally has nitric-oxide-mediated vasodilation and the strongest specific evidence in the old.

How to prescribe — "start low, go slow". Begin only when the patient is euvolaemic and not requiring intravenous inotropes. Start at a very low dose (bisoprolol 1.25 mg daily, carvedilol 3.125 mg twice daily, nebivolol 1.25 mg daily) and double at intervals of not less than two weeks to the maximum tolerated or target dose, checking heart rate, blood pressure, weight and symptoms at each step. Warn the patient that symptoms may transiently worsen in the first weeks. If fluid retention occurs, increase the diuretic rather than stopping the beta-blocker. Some beta-blocker is better than none — a low maintained dose is preferable to withdrawal.

Adverse effects and cautions in older adults. Bradycardia and heart block (particularly with coexisting sinus node disease, digoxin, amiodarone or verapamil), hypotension and falls, fatigue, worsening of heart failure during uptitration, cold peripheries and worsening claudication, masking of hypoglycaemia in insulin-treated diabetes, sleep disturbance and vivid dreams, and depression. Contraindications: second- or third-degree heart block without a pacemaker, symptomatic bradycardia, severe hypotension, cardiogenic shock and decompensated fluid overload. Asthma and COPD are no longer absolute contraindications — recent evidence reassures on the safety of cardioselective beta-blockers, and they should be used when required in asthmatic and COPD patients. Never withdraw abruptly, as rebound ischaemia and arrhythmia may result.

Where the evidence is weaker. In HFpEF, beta-blockers have no proven mortality benefit and are used chiefly for rate control in atrial fibrillation, angina or hypertension; excessive bradycardia may actually be harmful by limiting the chronotropic reserve that older patients already lack. In heart failure with atrial fibrillation, meta-analysis suggests the mortality benefit is attenuated compared with sinus rhythm, though beta-blockers remain useful for rate control. Their role is also limited in cardiac amyloidosis, where they are usually poorly tolerated.

The indication for beta-blockade after myocardial infarction has narrowed sharply — but the heart failure indication is untouched. REDUCE-AMI (NEJM 2024) found that in patients after acute myocardial infarction with a preserved ejection fraction (LVEF ≥ 50%) and no heart failure, long-term beta-blockade gave no reduction in death or recurrent infarction, and ABYSS (2024) found that interruption of beta-blockade after uncomplicated MI was not inferior for hard outcomes. The examinable message is that beta-blockers remain mandatory disease-modifying therapy in HFrEF at every age, but should no longer be continued indefinitely purely for a remote myocardial infarction with normal ventricular function — a useful deprescribing opportunity in the polypharmacy-burdened older patient.