Key Facts

Beta-blockers are versatile drugs with established mortality benefits in heart failure and post-MI. Understanding selectivity, contraindications, and the importance of gradual withdrawal is essential.

Pharmacology

• Beta-1 receptors: heart (↑ rate, ↑ contractility), kidney (↑ renin release)
• Beta-2 receptors: bronchial smooth muscle (relaxation), vascular smooth muscle (vasodilation), liver (glycogenolysis)
• Beta-1 selective agents: preferentially block beta-1 → cardiac effects with less bronchospasm; selectivity is dose-dependent (lost at high doses)
• Non-selective agents: block both beta-1 and beta-2 → cardiac + bronchial + vascular + metabolic effects
• Intrinsic sympathomimetic activity (ISA): pindolol, acebutolol — partial agonist activity; less bradycardia but less mortality benefit; rarely used now

Pathophysiology

• Beta-blockade → ↓ heart rate, ↓ contractility, ↓ AV conduction, ↓ renin → ↓ cardiac output, ↓ myocardial oxygen demand
• In heart failure: chronic sympathetic activation damages myocardium → beta-blockers reverse this (start low, go slow — initial transient worsening possible)
• Receptor up-regulation: chronic beta-blockade → increased receptor density → sudden withdrawal → exaggerated sympathetic response (rebound)

Indications

• Heart failure (HFrEF): bisoprolol, carvedilol, nebivolol — mortality benefit
• Post-MI: secondary prevention — reduce reinfarction and mortality
• Angina: reduce heart rate and myocardial oxygen demand
• Arrhythmias: rate control in AF (bisoprolol), SVT; class II antiarrhythmic
• Thyrotoxicosis: symptom control (tremor, tachycardia) — propranolol
• Migraine prophylaxis: propranolol 40–80 mg BD
• Portal hypertension: propranolol/carvedilol — reduce variceal bleeding risk
• Anxiety: propranolol 10–40 mg for situational anxiety (tremor, palpitations)
• Hypertension in pregnancy: labetalol (first-line)

Side Effects

• Bradycardia: excessive; may need dose reduction
• Fatigue, cold extremities: reduced cardiac output, peripheral vasoconstriction
• Bronchospasm: non-selective > selective; contraindicated in asthma
• Erectile dysfunction: can occur with any beta-blocker
• Hypoglycaemia masking: blocks sympathetic warning signs (tachycardia, tremor) in diabetics — caution
• Depression/sleep disturbance: lipophilic agents (propranolol) cross blood-brain barrier
• Worsening Raynaud's: peripheral beta-2 blockade → vasoconstriction

Red Flags

• Asthma + non-selective beta-blocker → severe bronchospasm — contraindicated
• Sudden withdrawal → rebound tachycardia, hypertension, angina, MI — always taper
• Heart block (2nd/3rd degree) — contraindicated
• Decompensated heart failure — do not initiate during acute decompensation; may worsen acutely

Before Starting

• Heart rate and BP: baseline; avoid if HR <60 or BP <90/60
• ECG: exclude heart block (2nd/3rd degree), bradyarrhythmia
• Respiratory history: exclude asthma; COPD — use beta-1 selective with caution
• Blood glucose: caution in insulin-treated diabetics (masks hypoglycaemia)

Monitoring

• Heart rate: target 55–70 bpm (heart failure, angina)
• BP: avoid hypotension
• Symptoms: fatigue, cold extremities, wheeze, mood changes
• In heart failure: start very low, uptitrate every 2 weeks; monitor for fluid retention

Special Tests

• Pulmonary function tests: if unclear whether asthma or COPD
• Echocardiogram: heart failure assessment (EF) to determine if beta-blocker indicated

Heart Failure (HFrEF)

• Bisoprolol: start 1.25 mg OD → uptitrate every 2 weeks → target 10 mg OD
• Carvedilol: start 3.125 mg BD → uptitrate → target 25 mg BD (50 mg BD if >85 kg)
• Nebivolol: alternative in elderly (SENIORS trial)
• Start when patient is stable (not acutely decompensated); temporary fluid retention may occur → continue

Angina

• Bisoprolol 5–10 mg OD or atenolol 50–100 mg OD: reduce heart rate → ↓ myocardial oxygen demand

AF Rate Control

• Bisoprolol 2.5–10 mg OD: first-line for rate control (NICE NG196)

Withdrawal

• NEVER stop abruptly: taper over 2–4 weeks to avoid rebound
• Reduce dose by 50% every 1–2 weeks

Overdose

• Bradycardia, hypotension, bronchospasm, hypoglycaemia
• Treatment: atropine 500 mcg IV (bradycardia), IV glucagon 5–10 mg (positive inotrope bypassing beta-receptor), IV fluids, consider insulin-glucose therapy

Referral Criteria

• Cardiology: heart failure initiation/uptitration, complex arrhythmias
• Respiratory: if beta-blocker needed but respiratory concerns

• CIBIS-II (bisoprolol in HF): 34% reduction in all-cause mortality
• COPERNICUS (carvedilol in severe HF): 35% mortality reduction
• Post-MI: beta-blockers reduce reinfarction by ~20–25% and mortality by ~20%
• Hypertension: no longer first-line (ASCOT-BPLA: atenolol-based inferior to amlodipine-based)
• Rebound on withdrawal: well-documented; gradual taper prevents complications

Beta-Blocker Selectivity Summary

Key Trials