Abstract 458: Inhibition of Interleukin-1 Activity Improves Coronary Flow, Endothelial Function and Arterial Wall Properties: A Randomized Cross-Over, Placebo-Controlled, Trial
Background: Interleukin-1 plays an important role in the pathophysiology and progression of inflammation and may be involved in regulation of coronary vasomotor tone. Anakinra, a human recombinant inerleukin-1a receptor antagonist, has been used as an anti-inflammatory agent in patients with rheumatoid arthritis. We investigated the effects of anakinra on endothelial function, arterial wall properties and coronary flow.
Methods: 19 patients (15 female, 4 male, median age 49 yrs) with rheumatoid arthritis were randomized to receive a single injection of anakinra (150mg sc) or placebo and after 48 hours (drug’s 5 half lives) the alternative treatment (placebo or anakinra respectively). Before and 3 hours after each s.c. injection, we assessed
the time integral of the coronary flow velocity (CF-VTI), the coronary flow reserve (CFR) of the LAD after adenosine infusion, and aortic strain, by means of echocardiography,
flow mediated endothelial-dependent dilation of the brachial artery (FMD) by ultrasonography
carotid to femoral artery pulse wave velocity using the Complior apparatus and
plasma levels of high sensitivity C-reactive protein. All patients continued treatment with anakinra and were reassessed one month later.
Results: During the acute phase of the study (pre- and 3 hours post injection), a significant improvement in FMD and in CF-VTI and aortic strain was observed in the anakinra arm, while no significant differences were observed in the placebo arm (table⇓, p<0.05). After one month treatment with anakinra, a further improvement in FMD and CF-VTI was demonstrated. In addition, C-reactive protein, arterial stiffness and aortic distensibility were significantly improved. No significant differences were observed in CFR.
Conclusion: IL-1a receptor antagonism improves coronary flow, endothelial function and arterial wall properties through reduction of inflammation.