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What to look for and treat in women with INOCA

(Ischemia and Non-Obstructive Coronary Artery disease): Microvascular Dysfunction

Cardiovasc Res. 2020 Feb 22.

Treatment of coronary microvascular dysfunction.

Bairey Merz CN1, Pepine CJ2, Shimokawa H3, Berry C4.

Author information

1 Barbra Streisand Women’s Heart Center, Smidt Heart Institute, Cedars-Sinai, 127 S. San Vicente Blvd, Suite A3600, Los Angeles, CA 90048, USA.

2 Division of Cardiovascular Medicine, University of Florida, 1329 SW 16th Street, PO Box 100288, Gainesville, FL 32610-0288, USA.

3 Division of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.

4 Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow G12 8QQ, UK.


Contemporary data indicate that patients with signs and symptoms of ischaemia and non-obstructive coronary artery disease (INOCA) often have coronary microvascular dysfunction (CMD) with elevated risk for adverse outcomes. Coronary endothelial (constriction with acetylcholine) and/or microvascular (limited coronary flow reserve with adenosine) dysfunction are well-documented, and extensive non-obstructive atherosclerosis is often present. Despite these data, patients with INOCA currently remain under-treated, in part, because existing management guidelines do not address this large, mostly female population due to the absence of evidence-based data. Relatively small sample-sized, short-term pilot studies of symptomatic mostly women, with INOCA, using intense medical therapies targeting endothelial, microvascular, and/or atherosclerosis mechanisms suggest symptom, ischaemia, and coronary vascular functional improvement, however, randomized, controlled outcome trials testing treatment strategies have not been completed. We review evidence regarding CMD pharmacotherapy. Potent statins in combination with angiotensin-converting enzyme inhibitor (ACE-I) or receptor blockers if intolerant, at maximally tolerated doses appear to improve angina, stress testing, myocardial perfusion, coronary endothelial function, and microvascular function. The Coronary Microvascular Angina trial supports invasive diagnostic testing with stratified therapy as an approach to improve symptoms and quality of life. The WARRIOR trial is testing intense medical therapy of high-intensity statin, maximally tolerated ACE-I plus aspirin on longer-term outcomes to provide evidence for guidelines. Novel treatments and those under development appear promising as the basis for future trial planning.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email:

KEYWORDS: Angina; CMD; Ischaemia; Women; INOCA


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