A randomized, placebo-controlled, double-blinded clinical trial of colchicine to improve vascular health in people living with HIV

Abstract

Objectives: People living with HIV (PWH) experience an increased burden of coronary artery disease (CAD) believed to be related, in part, to an interplay of chronically increased inflammation and traditional risk factors. Recent trials suggest cardiovascular benefits of the anti-inflammatory, colchicine, in HIV-seronegative CAD patients. However, the impact of colchicine on impaired vascular health, as measured by coronary endothelial function (CEF), an independent contributor to CAD, has not been studied in PWH. We tested the hypothesis that colchicine improves vascular health in PWH.

Design: This was a randomized, placebo-controlled, double-blinded trial in 81 PWH to test whether low-dose colchicine (0.6 mg daily) improves CEF over 8-24 weeks.

Methods: Coronary and systemic endothelial function and serum inflammatory markers were measured at baseline, and at 8 and 24 weeks. The primary endpoint was CEF, measured as the change in coronary blood flow from rest to that during an isometric handgrip exercise, an endothelial-dependent stressor, measured with non-invasive MRI at 8 weeks.

Results: Colchicine was well tolerated and not associated with increased adverse events. However, there were no significant improvements in coronary or systemic endothelial function or reductions in serum inflammatory markers at 8 or 24 weeks with colchicine as compared to placebo.

Conclusions: In PWH with no history of CAD, low-dose colchicine was well tolerated but did not improve impaired coronary endothelial function, a predictor of cardiovascular events. These findings suggest that this anti-inflammatory approach using colchicine in PWH does not improve vascular health, the central, early driver of coronary atherosclerosis.

Trial registration: ClinicalTrials.gov NCT02624180.

Conflict of interest statement

Declaration of interests: There are no conflicts of interests from any of the authors.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Figures

Figure 1:

Trial Flow Chart

Figure. 2:

Representative coronary artery MRI images for CEF. (A) A scout MRI obtained parallel to the right coronary artery (RCA) is shown with the location for subsequent cross-sectional imaging (yellow outline). (B) Image acquired along the yellow-outlined region in (A) with RCA in cross-section (white arrow). The dotted rectangle in B is magnified in subsequent panels and shows the region analyzed for cross-sectional area at rest (C) and during isometric handgrip exercise (IHE), D). Flow velocity images of the same segment at rest (E) and during IHE (F) using a phase contrast technique wherein signal darkness increases only slightly during IHE, indicating an impaired response. G and H: Relative changes (%) in coronary artery cross sectional area (CSA), and coronary blood-flow (CBF) using MRI during isometric handgrip exercise at 8 weeks (G) and 24 weeks (H). Percent change in coronary vasoreactive parameters with IHE are shown for those on colchicine (red) and placebo (blue). Error bars indicate standard error of the mean. There were no significant differences in coronary endothelial function parameters between the placebo and anti-inflammatory treatment at the 8 week (primary) en point. % CBF change was lower in the colchicine than placebo group (*p=0.05) at 24 weeks. Ao=aorta; LV=left ventricle, RV=right ventricle.

Figure 3:

Bar graphs showing serum biomarkers (mean values) at baseline and at 8 weeks after randomization to colchicine (red bars) or placebo (blue bars) in people living with HIV. Error bars indicate standard error of the mean. There were no significant differences in level of inflammatory biomarkers (A-F) between groups.