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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1850.)
© 2007 American Heart Association, Inc.

Thrombosis

Effects of Unfractionated Heparin and Glycoprotein IIb/IIIa Antagonists Versus Bivalirdin on Myeloperoxidase Release From Neutrophils

Guohong Li; Alison C. Keenan; Justin C. Young; Margaret J. Hall; Zehra Pamuklar; E. Magnus Ohman; Steven R. Steinhubl; Susan S. Smyth

From the Carolina Cardiovascular Biology Center (A.C.K., J.C.Y., S.S.S.) and the School of Public Health (M.J.H.), The University of North Carolina, Chapel Hill; the Department of Medicine, Division of Cardiology (E.M.O.), Duke University Medical School, Durham, North Carolina; and the Division of Cardiovascular Medicine (G.L., Z.P., S.R.S., S.S.S.), The Gill Heart Institute, The University of Kentucky, Lexington.

Correspondence to Susan Smyth, MD, PhD, Division of Cardiovascular Medicine, The Gill Heart Institute, 900 S. Limestone Street, 326 Charles T Wethington Building, Lexington, KY 40536-0200. E-mail SusanSmyth{at}uky.edu

Objectives— The objective of this study was to determine whether adjunctive therapy during percutaneous coronary intervention (PCI) affects markers of systemic inflammation or platelet activation. Despite different mechanisms of action, direct-thrombin inhibition with bivalirudin during PCI provided similar protection from periprocedural and chronic ischemic complications as compared with unfractionated heparin (UFH) plus planned use of GPIIb/IIIa antagonists in the REPLACE-2 and ACUITY trials.

Methods and Results— Patients undergoing nonurgent PCI of a native coronary artery were randomized to receive adjunctive therapy with bivalirudin or UFH+eptifibatide. Interleukin (IL)-6 and C-reactive protein (CRP) transiently increased in both groups after PCI. In the UFH+eptifibatide, but not the bivalirudin group, myeloperoxidase (MPO) levels were elevated 2.3-fold above baseline (P=0.004) immediately after PCI. In an in vitro assay, heparin and to a lesser extent enoxaparin, but not bivalirudin or eptifibatide, stimulated MPO release from and binding to neutrophils and neutrophil activation. A mouse model of endoluminal femoral artery denudation was used to investigate further the importance of MPO in the context of arterial injury.

Conclusions— Adjuvant therapy during PCI may have undesired effects on neutrophil activation, MPO release, and systemic inflammation.

Unfractionated heparin+eptifibatide was associated with higher myeloperoxidase levels after percutaneous coronary intervention. Heparin, but not bivalirudin, fondaparinux, or eptifibatide, increased MPO release from and binding to isolated neutrophils. These results indicate that adjuvant therapy during PCI may have undesired effects on neutrophil activation, MPO release, and systemic inflammation.

Key Words: platelets • neutrophils • myeloperoxidase • percutaneous coronary intervention • adjunctive therapy

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