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Thromb Haemost 2005; 93(03): 535-543
DOI: 10.1160/TH04-07-0464
Platelets and Blood Cells
Schattauer GmbH

Nitroaspirin plus clopidogrel versus aspirin plus clopidogrel against platelet thromboembolism and intimal thickening in mice

Stefania Momi
1   Department of Internal Medicine, Section of Internal and Cardiovascular Medicine
,
Simon C. Pitchford
1   Department of Internal Medicine, Section of Internal and Cardiovascular Medicine
,
Paolo F. Alberti
2   Department of Experimental Medicine and Biochemical Science, Section of Pathological Anatomy, University of Perugia, Perugia, Italy
,
Pietro Minuz
3   University of Verona, Department of Biomedical and Surgical Sciences, Verona, Italy
,
Piero Del Soldato
4   Nicox Research Institute, Milan, Italy
,
Paolo Gresele
1   Department of Internal Medicine, Section of Internal and Cardiovascular Medicine
› Author AffiliationsGrant support: This study was partially supported by a grant from NicOx Research Institute (Milan, Italy).
Further Information

Publication History

Received 30 July 2004

Accepted after resubmission 03 January 2005

Publication Date:
14 December 2017 (online)

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Summary

Clopidogrel plus aspirin is the treatment of choice for patients undergoing percutaneous, coronary interventions with stenting, but it does not prevent restenosis. NCX-4016, a nitric oxide-releasing aspirin (nitroaspirin), exerts a wider range of antiplatelet actions compared to aspirin, superior antithrombotic activity and reduces restenosis after arterial injury in animals. The aim of the present study was to compare the combination of nitroaspirin plus clopidogrel with aspirin plus clopidogrel in a model of platelet pulmonary thromboembolism, bleeding and intimal thickening in mice. Drugs were administered orally for 5 days; the antithrombotic effects were evaluated against collagen plus epinephrine-induced pulmonary thromboembolism, the haemorrhagic effects by tail transection bleeding time and the effects on neointima proliferation by histomorphology of photochemically injured femoral arteries. Lung platelet emboli were reduced significantly and more effectively by nitroaspirin plus clopidogrel (-56%, p< 0.05 vs control) than by aspirin plus clopidogrel (-26%, p< 0.05 vs control). Ex vivo platelet aggregation was inhibited maximally by nitroaspirin plus clopidogrel. Aspirin plus clopidogrel strikingly prolonged the bleeding time while nitroaspirin plus clopidogrel induced a lesser prolongation. Nitroaspirin plus clopidogrel significantly reduced intimal thickening of the femoral artery while aspirin plus clopidogrel was ineffective. Nitroaspirin plus clopidogrel is more effective and less prohaemorrhagic than aspirin plus clopidogrel in mice; provided these data are confirmed in other animal models, nitroaspirin plus clopidogrel may represent a new regimen to be tested in patients undergoing coronary revascularization procedures.

Keywords

Nitric oxide - platelet aggregation - pulmonary thromboembolism - restenosis - thromboxane

Piero Del Soldato is the former Executive Vice-President of the Science & Technology section of NicOx Research Institute, a pharmaceutical company manufacturing nitroaspirin.


 

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