Antianginal Drugs

Antianginal drugs relieve ischaemic chest pain by reducing myocardial oxygen demand (lower heart rate, preload, afterload or contractility) or improving supply (coronary vasodilation). They treat symptoms and do not all reduce events. Secondary prevention, with aspirin, a statin and an ACE inhibitor where indicated, is given alongside them.

Classification. Beta blockers, calcium channel blockers (dihydropyridine and non-dihydropyridine), organic nitrates, ivabradine, nicorandil, ranolazine and trimetazidine (limited availability).

Mechanism. Beta blockers and non-dihydropyridine calcium channel blockers lower heart rate and contractility. Dihydropyridines dilate arteries. Nitrates dilate veins and coronary arteries. Ivabradine inhibits the funny current in the sinus node. Nicorandil opens potassium channels and donates nitric oxide. Ranolazine blocks late sodium current and reduces calcium overload. Trimetazidine shifts myocardial metabolism toward glucose oxidation.

Types of angina. Effort angina (fixed stenosis), vasospastic angina (coronary spasm), and microvascular angina. Drug choice differs.

• Beta blockers: reduce events after infarction and are first line for effort angina.
• Calcium channel blockers: alternative first line; first choice in vasospastic angina.
• Nitrates: rapid relief and prophylaxis; tolerance develops.
• Ivabradine: rate lowering without hypotension; sinus rhythm only.
• Nicorandil: potassium channel opener with nitrate effect.
• Ranolazine: no effect on heart rate or blood pressure; useful when these are low.
• Trimetazidine: metabolic modulator; restricted use in some regions.

• Acute attack: glyceryl trinitrate sublingual spray 400 micrograms (1 to 2 puffs) or tablet 300 to 600 micrograms, repeated after 5 minutes. If pain persists 5 minutes after a second dose, treat as acute coronary syndrome and call emergency services.
• Prophylaxis, first step: beta blocker (bisoprolol 2.5 to 10 mg daily, metoprolol 50 to 200 mg daily, atenolol 50 to 100 mg daily) or rate-limiting calcium channel blocker (diltiazem 120 to 360 mg daily, verapamil 120 to 480 mg daily), aiming for a resting heart rate of 55 to 60 beats/minute.
• Second step: add a long-acting dihydropyridine (amlodipine 5 to 10 mg daily or modified-release nifedipine) to a beta blocker, or a beta blocker to a dihydropyridine. Avoid combining verapamil or diltiazem with a beta blocker.
• Third step: long-acting nitrate (isosorbide mononitrate 20 to 60 mg twice daily or 60 to 120 mg modified release once daily), ivabradine 5 to 7.5 mg twice daily, nicorandil 10 to 20 mg twice daily, or ranolazine 375 to 750 mg twice daily.
• Vasospastic angina: calcium channel blocker with or without nitrate; avoid nonselective beta blockers and high-dose aspirin.
• Refractory angina: revascularisation assessment, enhanced external counterpulsation, and specialist pain services.
• Selection: match to heart rate, blood pressure, ejection fraction, comorbidities and cost. Revascularisation is considered when symptoms persist on two drugs.

Contraindications. Class-specific: severe bradycardia or block (beta blockers, rate-limiting calcium channel blockers, ivabradine), reduced ejection fraction (verapamil, diltiazem), hypotension and aortic stenosis (nitrates, vasodilators), phosphodiesterase 5 inhibitor use (nitrates, nicorandil), QT prolongation and cirrhosis (ranolazine), and pregnancy (ivabradine).

Adverse effects. Bradycardia, fatigue, hypotension, headache, flushing, ankle oedema, constipation, visual phosphenes (ivabradine), mouth and gut ulceration (nicorandil), dizziness and constipation (ranolazine), and Parkinsonian symptoms (trimetazidine).

Interactions. Nitrates and nicorandil with sildenafil, tadalafil or riociguat cause profound hypotension. Ranolazine raises simvastatin exposure (limit simvastatin to 20 mg daily) and is affected by CYP3A4 inhibitors. Ivabradine is affected by CYP3A4 inhibitors and by verapamil or diltiazem. Short-acting nifedipine is avoided in angina.

Monitoring. Symptom diary and angina frequency, resting heart rate, blood pressure, electrocardiogram (QTc with ranolazine), kidney function, and liver function.

Referral and escalation. Angina at rest, crescendo pattern, new pain after infarction or syncope needs emergency assessment.

Special groups. Pregnancy: labetalol and nifedipine are used when needed, with specialist input. Older adults: lower starting doses and fall risk. Diabetes: silent ischaemia. Kidney disease: monitor ranolazine.