In Women With Symptoms of Cardiac Ischemia, Nonobstructive Coronary Arteries, and Microvascular Dysfunction, Angiotensin-Converting Enzyme Inhibition Is Associated With Improved Microvascular Function: A Double-Blind Randomized Study From the National Heart, Lung, and Blood Institute Women’s Ischemia Syndrome Evaluation (WISE)

Study Questions:

Does angiotensin-converting enzyme inhibition (ACE-I) improve coronary flow reserve (CFR) and angina symptoms among women with nonobstructive coronary artery disease (CAD)?


This was a substudy of 78 women enrolled in the Women’s Ischemia Syndrome Evaluation (WISE) study. WISE enrolled women (ages 21-75 years) with signs and symptoms of ischemia referred for coronary angiography. All women in this analysis had microvascular dysfunction (defined as a CFR <3.0 following adenosine), and no obstructive CAD on angiography. Multiple exclusion criteria were outlined including pregnancy or unwillingness to avoid pregnancy, uncontrolled hypertension, and left ventricular ejection fraction <35%. Women were randomized to either an ACE-I with quinapril or a placebo treatment group. The primary outcome of interest was CFR at 16 weeks adjusted for baseline characteristics and clinical site. A secondary outcome was improvement of angina symptoms assessed using the Seattle Angina Questionnaire.


Of the 78 women randomly assigned to treatment, 61 completed the 16-week angiogram, CFR measurement, and angina assessments (29 in the ACE-I group and 32 in the placebo group). The ACE-I group trended to be older, have lower body mass index, and were less likely to smoke and use nitrates. At 16 weeks, CFR improved more in the ACE-I group compared to the placebo group (p < 0.02). Both ACE-I treatment (p = 0.037) and CFR increase (p = 0.008) improved angina symptoms.


The investigators concluded that among women with nonobstructive CAD, ACE-I therapy appears to improve microvascular function, with an improvement in angina symptoms. The benefits appear to be limited to women with lower baseline CFR.


This small substudy from WISE provides interesting findings, which may result in improved management of patients with microvascular disease. Further study is warranted.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Atherosclerotic Disease (CAD/PAD), Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Nuclear Imaging, Hypertension

Keywords: Coronary Artery Disease, Women, Myocardial Ischemia, Body Mass Index, Coronary Angiography, Tetrahydroisoquinolines, Ventricular Function, Hypertension, United States

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