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

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1850-1856
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume27
Issue number8
DOIs
StatePublished - Aug 1 2007

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Platelet Glycoprotein GPIIb-IIIa Complex
Percutaneous Coronary Intervention
Peroxidase
Heparin
Neutrophils
Neutrophil Activation
Inflammation
Enoxaparin
Platelet Activation
Femoral Artery
Thrombin
C-Reactive Protein
Interleukin-6
Coronary Vessels
Therapeutics
bivalirudin
Wounds and Injuries
eptifibatide

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Li, Guohong ; Keenan, Alison C. ; Young, Justin C. ; Hall, Margaret J. ; Pamuklar, Zehra ; Ohman, E. Magnus ; Steinhubl, Steven R. ; Smyth, Susan S. / Effects of unfractionated heparin and glycoprotein IIb/IIIa antagonists versus bivalirdin on myeloperoxidase release from neutrophils. In: Arteriosclerosis, thrombosis, and vascular biology. 2007 ; Vol. 27, No. 8. pp. 1850-1856.
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abstract = "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.",
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Effects of unfractionated heparin and glycoprotein IIb/IIIa antagonists versus bivalirdin on myeloperoxidase release from neutrophils. / Li, Guohong; Keenan, Alison C.; Young, Justin C.; Hall, Margaret J.; Pamuklar, Zehra; Ohman, E. Magnus; Steinhubl, Steven R.; Smyth, Susan S.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 27, No. 8, 01.08.2007, p. 1850-1856.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effects of unfractionated heparin and glycoprotein IIb/IIIa antagonists versus bivalirdin on myeloperoxidase release from neutrophils

AU - Li, Guohong

AU - Keenan, Alison C.

AU - Young, Justin C.

AU - Hall, Margaret J.

AU - Pamuklar, Zehra

AU - Ohman, E. Magnus

AU - Steinhubl, Steven R.

AU - Smyth, Susan S.

PY - 2007/8/1

Y1 - 2007/8/1

N2 - 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.

AB - 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.

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U2 - 10.1161/ATVBAHA.107.144576

DO - 10.1161/ATVBAHA.107.144576

M3 - Article

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SP - 1850

EP - 1856

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

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