Sustained Platelet Glycoprotein IIb/IIIa Blockade With Oral Xemilofiban in 170 Patients After Coronary Stent Deployment

Kereiakes, Dean J.; Kleiman, Neal S.; Ferguson, James J.; Runyon, John Paul; Broderick, Thomas M.; Higby, Nancy A.; Martin, Linda H.; Hantsbarger, G; McDonald, Shawn; Anders, Robert J.

doi:10.1161/01.cir.96.4.1117

Cited by 66 publications

(17 citation statements)

References 16 publications

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“…Sustained inhibition of platelet aggregation with xemilofiban has been demonstrated in patients with unstable angina 32 and in patients after coronary stent deployment. 33 In summary, xemilofiban, a novel GP IIb/IIIa receptor antagonist, inhibits ex vivo platelet aggregation, prevents occlusive thrombus formation, and prevents CFVs in response to continuous electrical injury in a canine model of arterial thrombosis. In addition, coadministration of HD ASA provides an observed increase in the antithrombotic response and in the level of protection against CFVs by a dose of xemilofiban that when administered alone has limited efficacy in this model.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Oral Xemilofiban in Arterial Thrombosis in Dogs

Frederick¹,

Suleymanov²,

Szalony³

et al. 1998

Circulation

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Background-Inhibition of platelet aggregation by preventing the binding of fibrinogen to glycoprotein (GP) IIb/IIIa on activated platelets results in antithrombotic activity. We report on the antithrombotic effect of xemilofiban (SC-54684A), an oral GP IIb/IIIa antagonist, administered alone or with aspirin (ASA) in an acute thrombosis model. Methods and Results-Conscious dogs were treated with xemilofiban (1.25, 2.5, 5.0, or 6 mg/kg, nϭ6); low-dose (LD, 81 mg) ASA, nϭ7; high-dose (HD, 162 mg) ASA, nϭ6; xemilofibran 1.25 mg/kg plus LD ASA, nϭ6; xemilofibran 1.25 mg/kg plus HD ASA, nϭ6; or placebo, nϭ7. Dogs were anesthetized 60 minutes later, and the effects of the treatments were evaluated after electrolytic injury (250 A for 180 minutes) in the left circumflex coronary artery. Bleeding time (BT) was assessed in a separate study. Incidence of thrombosis was reduced (PϽ0.05) by xemilofiban Ն2.5 mg/kg, HD ASA, or xemilofiban 1.25 mg/kg plus HD ASA compared with placebo. Xemilofiban Ն2.5 mg/kg or xemilofiban 1.25 mg/kg plus HD ASA significantly increased time to occlusion, inhibited ex vivo platelet aggregation to collagen Ͼ90%, and prevented or decreased (PϽ0.05) cyclic flow variations (CFVs) compared with placebo. BT was increased (PϽ0.05) with xemilofiban Ն2.5 mg/kg but not with xemilofiban 1.25 mg/kg plus HD ASA. Conclusions-Xemilofiban Ն2.5 mg/kg, HD ASA, or xemilofiban 1.25 mg/kg plus HD ASA significantly reduced the incidence of thrombosis. These doses of xemilofiban or xemilofiban 1.25 mg/kg plus HD ASA increased time to occlusion, inhibited ex vivo platelet aggregation by Ͼ90%, and prevented or reduced CFVs. Xemilofiban Ն2.5 mg/kg but not xemilofiban 1.25 mg/kg plus HD ASA significantly increased BT. (Circulation. 1998;98:813-820.)

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Section: Discussionmentioning

confidence: 99%

Protective Effect of Oral Xemilofiban in Arterial Thrombosis in Dogs

Frederick¹,

Suleymanov²,

Szalony³

et al. 1998

Circulation

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“…In this case, even a long-term medication with the antiplatelet agents ASA and ticlopidine was not able to reduce the increased platelet activation sufficiently. A potential therapeutic alternative for this group of patients could be the new generation of orally available synthetic antiplatelet agents, which bind to the platelet glycoprotein receptor IIb/IIIa by mimicking the RGD-sequence of the ligand fibrinogen [44][45][46]. This alternative concept of a long term antithrombotic therapy awaits evaluation in large clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Analysis of vessel wall morphology, blood flow velocity, and the hemostatic system in a patient with a large intracoronary thrombus

Haude

Altmann

Eick

et al. 1998

Cathet. Cardiovasc. Diagn.

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A patient with AMI caused by a large thrombus in the proximal LAD was successfully treated with PTCA and an intracoronary lysis combined with the platelet‐receptor antagonist c7E3. Analysis of cellular hemostasis after 1 and 6 months revealed a sustained platelet activation despite combined anti‐platelet therapy with ASA and ticlopidine. A progredient slow‐flow phenomenon appeared during control angiographies, confirmed by intracoronary Doppler examination. Cathet. Cardiovasc. Diagn. 43:298–305, 1998. © 1998 Wiley‐Liss, Inc.

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“…Several studies established the doseresponse relationship for xemilofiban [19]. A clear dosedependent increase in platelet aggregation inhibition was documented with xemilofiban in patients undergoing PCI.…”

Section: The Oral Glycoprotein Iib/iiia Inhibitorsmentioning

confidence: 99%

Oral glycoprotein IIb/IIIa antagonists in coronary artery disease

Chew

Bhatt

2001

Curr Cardiol Rep

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Despite the efficacy of intravenous glycoprotein IIb/IIIa inhibition in patients undergoing percutaneous coronary intervention and those presenting with acute coronary syndromes, the application of oral glycoprotein IIb/IIIa inhibition to the chronic management of coronary artery disease has not met with the same success. To explain these results, factors related to dosing, and inadequate inhibition or activation of platelet pro-coagulant activity have been recently suggested. However, although the disparity between intravenous and oral glycoprotein IIb/IIIa experience remains largely enigmatic, the discordant effect on ischemic endpoints observed within the phase III oral glycoprotein IIb/IIIa inhibitor trials potentially implicates a mechanism unrelated to platelet function.

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Sustained Platelet Glycoprotein IIb/IIIa Blockade With Oral Xemilofiban in 170 Patients After Coronary Stent Deployment

Cited by 66 publications

References 16 publications

Protective Effect of Oral Xemilofiban in Arterial Thrombosis in Dogs

Protective Effect of Oral Xemilofiban in Arterial Thrombosis in Dogs

Analysis of vessel wall morphology, blood flow velocity, and the hemostatic system in a patient with a large intracoronary thrombus

Oral glycoprotein IIb/IIIa antagonists in coronary artery disease

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