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
I_f 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.