Abstract 234: Bivalirudin Adversely Affects Endothelial NO Bioavailability By Vascular Immoblization Of Myeloperoxidase
Background: Myeloperoxidase (MPO), has been shown to oxidize endothelial derived nitric oxide (NO). Heparins mobilize vascular bound MPO and thereby increase endothelial NO bioavailability. Here we investigated whether bivalirudin, a direct thrombin inhibitor with comparable anticoagulant properties as heparins, also interacts with MPO thus affecting endothelial NO homoeostasis.
Methods and results: In a single center double blind randomized study, 30 patients with stable coronary artery disease either received bivalirudin (n=15) or unfractionated heparin (UFH, n=15) prior to undergoing elective PCI. MPO levels were determined before and after drug administration, as was flow mediated dilation (FMD). Whereas patients receiving UFH showed an increase in MPO levels (2.63 [IR: 1.94–3.62] to 4.24 [IR: 2.44 –5.34], p<0.01) and improved FMD (7.20±3.54 to 9.59±4.06, p<0.01), patients receiving bivalirudin exhibited a significant decrease of MPO levels (3.65 [IR: 2.36 –5.03] to 3.22 [IR: 2.06 – 4.27], p=0.03), which was accompanied by deteriorated FMD (6.65±2.68 to 5.64±2.88%, p=0.02). Ex-vivo studies revealed increased binding of MPO to fibronectin in the presence of bivalirudin in contrast to UFH.
Conclusions: Bivalirudin adversely affects endothelial NO bioavailability with immobilization of circulating MPO to the vessel wall emerging as a critical mechanism. These results not only illustrate extra-coagulant properties of heparins and thrombin inhibitors, but further underscore the critical role of neutrophil-derived MPO as a mediator of vascular function.