AUTHOR=Hays Allison G. , Schär Michael , Bonanno Gabriele , Lai Shenghan , Meyer Joseph , Afework Yohannes , Steinberg Angela , Stradley Samuel , Gerstenblith Gary , Weiss Robert G. 

TITLE=Randomized Trial of Anti-inflammatory Medications and Coronary Endothelial Dysfunction in Patients With Stable Coronary Disease

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.728654

DOI=10.3389/fcvm.2021.728654

ISSN=2297-055X

ABSTRACT=<p><bold>Aims:</bold> Inflammation plays a critical role in the pathogenesis of coronary artery disease (CAD), however the impact of anti-inflammatory therapies to reduce those processes which promote atherosclerosis in CAD patients is unknown. We aimed to test the hypothesis that anti-inflammatory approaches improve impaired coronary endothelial function (CEF), a driver of coronary atherosclerosis, in stable CAD patients.</p><p><bold>Methods and Results:</bold> We performed a single-center, randomized, placebo-controlled, double-blinded trial to assess whether low dose methotrexate (MTX), low dose colchicine (LDC), and/or their combination (MTX+LDC), improves CEF using non-invasive MRI measures in patients with stable CAD (<italic>N</italic> = 94). The primary endpoint was the MRI-detected change in coronary cross-sectional area from rest to isometric handgrip exercise (IHE), a predominantly nitric oxide-dependent endothelial dependent stressor. Coronary and systemic endothelial endpoints, and serum inflammatory markers, were collected at baseline, 8 and 24 weeks. Anti-inflammatory study drugs were well-tolerated. There were no significant differences in any of the CEF parameters among the four groups (MTX, LDC, MTX+LDC, placebo) at 8 or 24 weeks. Serum markers of inflammation and systemic endothelial function measures were also not significantly different among the groups.</p><p><bold>Conclusion:</bold> This is the first study to examine the effects of the anti-inflammatory approaches using MTX, LDC, and/or the combination in stable CAD patients on CEF, a marker of vascular health and the primary endpoint of the study. Although these anti-inflammatory approaches were relatively well-tolerated, they did not improve coronary endothelial function in patients with stable CAD.</p><p><bold>Clinical Trial Registration:</bold><ext-link ext-link-type="uri" xlink:href="https://www.clinicaltrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">www.clinicaltrials.gov</ext-link>, identifier: NCT02366091.</p>