Table 2: Guideline-recommended Treatments Based on Clinical Endotype.

Diagnosis	Treatment	Mechanism of Effect
Microvascular angina	β-blockers (nebivolol 2.5–10 mg once daily)	↓ Myocardial oxygen consumption Antioxidant properties
	Calcium-channel blockers (amlodipine 10 mg once daily)	Vascular smooth muscle relaxation ↓ Myocardial oxygen consumption
	Nicorandil (10–20 mg twice daily)	Coronary microvascular dilator
	Ranolazine (375–750 mg twice daily)	Improves microvascular perfusion reserve index in microvascular angina with reduced CFR
	Trimetazidine (35 mg twice daily)	Increases cellular tolerance to ischaemia by maintaining homeostasis
	ACE inhibitors (ramipril 2.5–10 mg once daily); angiotensin-receptor blockers if intolerant	Improves CFR ↓ Workload May improve small vessel remodelling
Vasospastic angina	Calcium channel blockers (verapamil 240 mg once daily or diltiazem 120–360 mg daily)	↓ Spontaneous and inducible epicardial coronary spasm via smooth muscle relaxation ↓ Myocardial oxygen consumption
	Nitrates (isosorbide mononitrate 20–120 mg daily)	↓ Spontaneous and inducible coronary spasm via epicardial vasodilatation ↓ myocardial oxygen consumption
	Nicorandil (10–20 mg twice daily)	Coronary vasodilator effect
Mixed microvascular and vasospastic angina	Calcium channel blockers (amlodipine 10 mg once daily, diltiazem 90 mg twice daily or verapamil 240 mg once daily)	Vascular smooth muscle relaxation ↓ Myocardial oxygen consumption
	Nicorandil (10–20 mg twice daily)	Coronary microvascular dilator
	Trimetazidine (35 mg twice daily)	Increases cellular tolerance to ischaemia by maintaining homeostasis
	ACE inhibitors (ramipril 2.5–10 mg); angiotensin-receptor blockers if intolerant	Improves CFR ↓ Workload May improve small vessel remodelling
Non-cardiac symptoms	Discontinue antianginal medication; consider continuing cardiovascular risk reduction medication (e.g. statin) if coronary artery disease present	Cessation of unnecessary polypharmacy Continue cardiovascular risk reduction Consider referral to alternative specialty if appropriate
Cardiovascular risk reduction	Statins (e.g. atorvastatin 20–80 mg)	Improve coronary endothelial function Reduced vascular inflammation
	Antihypertensives	As per current hypertension guidelines
	Lifestyle: smoking cessation, exercise, cardiac rehabilitation, Mediterranean diet, cognitive behavioural therapy	Improved exercise capacity and cardiac conditioning, weight reduction if overweight

Summary of European Association of Percutaneous Cardiovascular Interventions expert consensus[3] and European Society of Cardiology chronic coronary syndromes 2019 guideline[4] for recommended treatment based on clinical endotype. CFR = coronary flow reserve. Adapted from: Kunadian et al. 2020.[3] Used with permission from Oxford University Press.