Extended Inhibition of Platelet Aggregation With the Orally Active Platelet Inhibitor SC-54684A

Szalony, James A.; Haas, Neal F.; Salyers, Anita K.; Taite, Beatrice B.; Nicholson, Nancy S.; Mehrotra, Devan V.; Feigen, Larry P.

doi:10.1161/01.cir.91.2.411

Cited by 34 publications

(18 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These strategies will probably widen the indications for long term platelet inhibition. Results achieved with the intravenously administered monoclonal antibody abciximab, have demonstrated that the efficacy of lIb/IlIa antagonists is additive to that of aspirinJ15] Oral lIb/III antagonists have already been shown to induce dose-dependent inhibition of platelet aggregation for an extended period of time [53] and are currently in clinical development. Long term treatment with these compounds might be beneficial in indications which aspirin lacks efficacy, such as in the prevention of late thrombotic events and/or restenosis following coronary angioplasty.…”

Section: Resultsmentioning

confidence: 99%

Long Term Aspirin in the Prevention of Cardiovascular Disorders

Catella-Lawson

FitzGerald

1995

Drug Safety

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

Long Term Aspirin in the Prevention of Cardiovascular Disorders

Catella-Lawson

FitzGerald

1995

Drug Safety

View full text Add to dashboard Cite

“…3 A previous study demonstrated that administration of xemilofiban to conscious dogs resulted in dose-dependent antiplatelet activity and a high level of bioavailability. 10 In this report, we assessed for the first time the antithrombotic effectiveness of orally administered xemilofiban or xemilofiban with ASA in a canine model of coronary artery thrombosis. This experimental model allowed us to determine the efficacy of the test agents for prevention of occlusive thrombus formation in response to electrolytic damage of the intimal surface of the LCx.…”

Section: Discussionmentioning

confidence: 99%

“…9 Initial animal studies with xemilofiban demonstrated its effectiveness as an antiplatelet agent. 10 Accordingly, the present investigation determines the antithrombotic activity of orally administered xemilofiban in a canine model of occlusive coro-nary artery thrombosis 9 and tests the hypothesis that targeted levels of inhibition of platelet aggregation by xemilofiban prevent thrombotic occlusion. Moreover, the present experiments determine the antithrombotic effect of a minimally effective dose of xemilofiban combined with oral ASA.…”

mentioning

confidence: 99%

Protective Effect of Oral Xemilofiban in Arterial Thrombosis in Dogs

Frederick¹,

Suleymanov²,

Szalony³

et al. 1998

Circulation

Self Cite

View full text Add to dashboard Cite

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.)

show abstract

“…The active metabolite SC-54701A is a potent inhibitor of GP IIb/IIIa. 17 A dose-finding study (5 to 20 mg xemilofiban orally bid) after coronary stent deployment in 170 patients, all on aspirin, produced Ͼ50% platelet inhibition at a dose of 10 mg BID. 18 In this small study, no episodes of major bleeding occurred.…”

Section: Eptifibatidementioning

confidence: 99%

Synthetic Inhibitors of Platelet Glycoprotein IIb/IIIa in Clinical Development

Verstraete

2000

Circulation

View full text Add to dashboard Cite

Activation of the platelet glycoprotein (GP IIb/IIIa) receptor on the platelet surface is the final pathway of platelet aggregation, regardless of the initiating stimulus. Inhibitors of GP IIb/IIIa receptors include monoclonal antibodies (abciximab) against this receptor and peptidic and nonpeptidic synthetic specific receptor blockers. Abciximab exchanges between and binds to platelets for as long as 2 weeks, whereas synthetic GP IIb/IIIa inhibitors inhibit ex vivo platelet aggregation for only a few hours after the end of infusion, but some have the advantage of also being orally active. In the secondary prevention of atherothrombosis, large-scale trials were successfully conducted with aspirin, dipyridamole, ticlopidine, and clopidogrel. In the first large-scale trials with GP IIb/IIIa inhibitors, abciximab was investigated. In aggregate, synthetic GP IIb/IIIa inhibitors, combined with aspirin and heparin, were shown to reduce ischemic events in patients with high- and low-risk coronary intervention, stents, unstable angina, and non-Q-wave infarction. With short-term use of synthetic GP IIb/IIIa inhibitors, there is no suppression of clinical evident restenosis 6 months after the end of treatment. With the doses currently used, bleeding occurs more often with the synthetic GP IIb/IIIa inhibitors (used for 3 days) than with abciximab (used for 12 hours), but there are no direct comparisons between these drugs.

show abstract

Extended Inhibition of Platelet Aggregation With the Orally Active Platelet Inhibitor SC-54684A

Cited by 34 publications

References 16 publications

Long Term Aspirin in the Prevention of Cardiovascular Disorders

Long Term Aspirin in the Prevention of Cardiovascular Disorders

Protective Effect of Oral Xemilofiban in Arterial Thrombosis in Dogs

Synthetic Inhibitors of Platelet Glycoprotein IIb/IIIa in Clinical Development

Contact Info

Product

Resources

About