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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)?
Methods:
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.
Results:
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.
Conclusions:
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.
Perspective:
This small substudy from WISE provides interesting findings, which may result in improved management of patients with microvascular disease. Further study is warranted.
Keywords: Coronary Artery Disease, Women, Myocardial Ischemia, Body Mass Index, Coronary Angiography, Tetrahydroisoquinolines, Ventricular Function, Hypertension, United States
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