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with ranolazine, an antianginal agent that improves myocyte relaxation and ventricular compliance by decreasing sodium and calcium overload.983 Spinal cord stimulation is an option for patients who remain refractory after medical therapy.984 There are currently several studies evaluating therapies specific to ANOCA/INOCA. The Women’s IschemiA Trial to Reduce Events in Non-ObstRuctIve CORonary Artery Disease (WARRIOR, NCT03417388) is currently enrolling subjects in a multicentre, prospective, randomized, blinded outcome evaluation to assess intensive statin and ACE-I/ARB therapy (ischaemia-intensive medical therapy) vs. usual care on MACE in symptomatic women with ANOCA. The Precision Medicine with Zibotentan in Microvascular Angina (PRIZE) trial holds future promise (NCT04097314). Zibotentan is an oral, endothelin A receptor antagonist that may provide benefit by opposing the reported vasoconstrictor response of coronary microvessels to endothelin. Endothelial dysfunction and co-existing atherosclerosis Nutrition Exercise Coping with stress Hypertension Dyslipidaemia Diabetes mellitus 2 3 Weight management Smoking cessation Consider statins and ACEi Abnormal vasodilation Microvascular Abnormal vasoconstriction Microvascular Epicardial 1 Medical treatment based on pathophysiological endotypes Lifestyle Risk factors Treatment of ANOCA/INOCA CCB Nitrates Nicorandil CCB 2nd CCB Nitrates Beta-blocker CCB Ranolazine Trimetazidine Ivabradine Figure 15 Treatment of angina/ischaemia with non-obstructive coronary arteries. ACE-I, angiotensin-converting enzyme inhibitor; ANOCA, angina with non-obstructive coronary arteries; ARB, angiotensin receptor blocker; CCB, calcium channel blocker; INOCA, ischaemia with non-obstructive coronary arteries. Treatment of ANOCA/INOCA patients includes lifestyle modification, management of cardiovascular risk factors, and antianginal treatment according to underlying endotypes. Note: endotypes frequently overlap, requiring combined medical therapy. Downloaded from academic.oup.com/eurheartj/article/45/36/3415/7743115 by guest on 07 October 2026