Effects of unfractionated heparin and glycoprotein IIb/IIIa antagonists versus bivalirdin on myeloperoxidase release from neutrophils

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.