TY - JOUR
T1 - Treatment of coronary microvascular dysfunction
AU - Bairey Merz, C. Noel
AU - Pepine, Carl J.
AU - Shimokawa, Hiroki
AU - Berry, Colin
N1 - Funding Information:
This work was supported by an unrestricted research grant from Gilead Sciences, and contracts from the National Heart, Lung and Blood Institutes (nos. N01-HV-68161, N01-HV-68162, N01-HV-68163, N01-HV-68164, grants U0164829, U01 HL649141, U01 HL649241, K23HL105787, T32HL69751, R01 HL090957, 1R03AG032631), the National Institute on Aging, GCRC (MO1-RR00425), the National Center for Research Resources, the National Center for Advancing Translational Sciences (UL1TR000124), the Edythe L. Broad and the Constance Austin Women’s Heart Research Fellowships, Cedars-Sinai Medical Center, Los Angeles, California, the Barbra Streisand Women’s Cardiovascular Research and Education Program, Cedars-Sinai Medical Center, Los Angeles, the Erika Glazer Women’s Heart Health Project, and the Adelson Family Foundation,
Funding Information:
Cedars-Sinai Medical Center, Los Angeles, California. C.J.P. receives support from National Heart, Lung and Blood Institutes through grantsHL087366 (University of Florida Regional Clinical Center for the Cardiovascular Cell Therapy Research Network), HL132448 (Brain-Gut Microbiome-Immune Axis in Hypertension), and HL033610 (Angiotensin and Neuroimmune Activation in Hypertension); the Gatorade Trust through funds distributed by the University of Florida, Department of Medicine; National Center for Advancing Translational Sciences—University of Florida Clinical and Translational Science UL1TR001427; PCORnet-OneFlorida Clinical Research Consortium CDRN-1501-26692; and US Dept. of Defense PR161603 (WARRIOR). H.S. is supported by the Japan Heart Foundation, the Japan Society for Promotion of Science (JSPS). C.B. acknowledges research support from the British Heart Foundation (PG/17/2532884; RE/18/ 6134217) and Medical Research Council (MR/S005714/1).
Publisher Copyright:
© 2020 Published on behalf of the European Society of Cardiology. All rights reserved.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - 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.
AB - 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.
KW - Angina
KW - CMD
KW - INOCA
KW - Ischaemia
KW - Women
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U2 - 10.1093/cvr/cvaa006
DO - 10.1093/cvr/cvaa006
M3 - Review article
C2 - 32087007
AN - SCOPUS:85081553843
SN - 0008-6363
VL - 116
SP - 856
EP - 870
JO - Cardiovascular Research
JF - Cardiovascular Research
IS - 4
ER -