Table 2.

Angina pharmacotherapy

Treatment	Angina type	Example	Investigation	Mechanism of action	Common side-effects
ß-blockers	MVA, CAD	Bisoprolol: 1.25–10 mg	Reduced CFR and/or structural microvascular dysfunction (raised microvascular resistance)	Reduction in myocardial oxygen consumption	Fatigue, blurred vision, cold hands
Calcium channel antagonists	All	Dihydropyridine (amlodipine: 2.5–10 mg daily) Non-dihydropyridine (verapamil: 40–240 or diltiazem up to 500 mg; controlled release)	Propensity to coronary vasospasm (epicardial and/or microvascular)	↓ spontaneous and inducible coronary spasm via vascular smooth muscle relaxation and ↓ oxygen demand Vascular smooth muscle relaxation, reduction in myocardial oxygen consumption	Constipation, ankle swelling, flushing
Vasodilators
Nitrates	CAD, VSA	Isosorbid mononitrate: 30–120 mg one time a day (controlled released)	Propensity to epicardial coronary vasospasm	↓ spontaneous and inducible coronary spasm via large epicardial vasodilation, ↓ oxygen demand. Lack of efficacy in microvascular angina with potential deleterious effect	Headaches, dizziness, flushing
Nicorandil	All	Nicorandil: 5–30 mg two times a day	All	Potassium channel activator with coronary microvascular dilatory effect	Dizziness, flushing, weakness, nausea
Rho kinase inhibitors	VSA, CMD	Fasudil: 5–20 mg; three times a day	Epicardial and/or microvascular vasospasm	Reduce calcium sensitisation of vascular smooth muscle, maintains coronary vasodilation	Rashes, flushing, hypotension
Late Na+Current Inhibitors	MVA, CAD	Ranolazine: 375–500 mg two times a day	Reduced CFR	Improves MPRi in patients with MVA and reduced CFR	Nausea, dizziness, headache
If channel blockers	CAD, MVA	Ivabradine: 2.5–7.5 mg two times a day	All	Ivabradine has shown anti-ischaemic and antianginal activity	Bradycardia, AF, headache
Partial fatty-acid oxidation inhibitors	CAD, MVA	Perhexiline: 50–400 mg daily or Trimetazidine	Plasma concentration required for dose titration.	Perhexiline Inhibits carnitine O-palmitoyltransferase 1 and 2, which transfer free fatty acid from the cytosol into mitochondria.	Dizziness, unsteady, nausea and vomiting
Improved endothelial function/pleiotropic
ACE inhibitors	MVA, CAD	Ramipril: 2.5–10 mg daily	Hyper-reactivity to stimuli (eg, acetylcholine, exercise, stress)	Improve CFR, reduce workload, may improve small vessel remodelling. Improves endothelial vasomotor dysfunction	Cough, renal impairment, hyperkalaemia
Statins	All	Atorvastatin: 10–80 mg daily Rosuvastatin: 5–40 mg daily	All	Improved coronary endothelial function reduced vascular inflammation	Myalgia, headache, cramps
Hormone-replacement therapy*	MVA	Oestradiol: 1 mg daily	Angina in early menopause	Oestrogen therapy improves endothelial function short-term in CMD	↑ Risk of breast cancer, marginally ↑ risk of CVD
Tricyclic antidepressants (TCA)	MVA with abnormal pain processing	Amitriptyline: 5–10 mg nocte Imipramine: 10–200 mg daily	All	Counteracts enhanced nociception. Thought to exert an analgesic effect on the visceral component associated with cardiac pain.	Blurred vision, dry mouth, drowsiness, impaired coordination
Non-pharmacological	All	Smoking cessation, Exercise, cardiac rehabilitation, Mediterranean diet, cognitive behavioural therapy, weight loss, Yoga	Metabolic syndrome, endothelial dysfunction, cardiovascular risk factors, anxiety/depression		Adjunctive non-pharmacological interventions

*May be helpful in some postmenopausal women. More information on experimentary pharmacotherapy in refractory angina can be found in review by Henry et al.⁶²

CAD, angina with obstructive coronary artery disease; MPRi, myocardial perfusion reserve index; MVA, microvascular angina; VSA, vasospastic angina.