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Drug Evaluation

Lotrafiban: an oral platelet glycoprotein IIb/IIIa blocker

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Pages 2673-2687 | Published online: 23 Feb 2005

Bibliography

  • MARSO SP, LINCOFF AM, ELLIS SG et al.: Optimizing thepercutaneous interventional outcomes for patients with diabetes mellitus - Results of the EPISTENT (Evaluation of Platelet I1b/Illa inhibitor for Stenting Trial) diabetic substudy. Circulation (1999) 100:2477–2484.
  • THE EPILOG INVESTIGATORS: Platelet glycoproteinDb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. N Engl. J. Med. (1997) 336:1689–1696.
  • •Large scale trial of abciximab in patients undergoing percutaneous coronary intervention, demonstrating a 56% reduction in the primary composite clinical end-point of the trial.
  • TOPOL EJ, MARK DB, LINCOFF AM et al.: Outcomes at 1 year and economic implications of platelet glycopro-tein I1b/Illa blockade in patients undergoing coronary stenting: results from a multicentre randomised trial. Lancet (1999) 354: 2019-2024.
  • TOPOL EJ, BYZOVA TV, PLOW EF: Platelet GPI1b-Illa blockers. Lancet (1999) 353:227–231.
  • ••Review of the history of platelet and GPIIb/IIIa blockadestudies, including basic research, clinical trials and issues to be resolved in future.
  • LINCOFF AM, CALIFF RM, TOPOL EJ: Platelet glycopro- tein I1b/Illa receptor blockade in coronary artery disease. J. Am. Coll Cardiol (2000) 35:1103–1115.
  • ••Over 33,000 patients were included in analysing 11 large-scale, placebo-controlled trials of these agents. Blockade of the platelet glycoprotein IIb/IIIa receptor reduces ischaemic complications when used as an adjunct to percutaneous coronary intervention or the management of acute ischaemic syndromes.
  • CANNON CP, MCCABE CH, BORZAK S et al.: Randomized trial of an oral platelet glycoprotein lib Alla antago-nist, sibrafiban, in patients after an acute coronary syndrome: Results of the TIM1 12 trial. Circulation (1998) 97 (0340–349.
  • KEREIAKES DJ, KLEIMAN NS, FERGUSON JJ et al: Pharma-codynamic efficacy, clinical safety and outcomes after prolonged platelet Glycoprotein Db/Illa receptor blockade with oral xemilofiban: results of a multicenter, placebo-controlled, randomized trial. Circulation (1998) 98:1268–1278.
  • •A multicentre, placebo-controlled, randomised Phase II trial of oral GPIIb/IIIa blocker xemilofiban, demonstrating dose-related levels of platelet inhibition.
  • AKKERHUIS M, VAN DER ZWAAN C, WILCOX RG et al: Troponin-1 identifies patients with unstable coronary artery disease who benefit from long-term oral glycoprotein I1b/Illa inhibition: the FROST Study. Circulation (1999) 1 00 (Suppl. I) :292.
  • HARRINGTON RA, ARMSTRONG PW, GRAFFAGNINO C etal.: Dose-finding, safety and tolerability study of an oral platelet glycoprotein I1b/Illa inhibitor, lotrafiban, in patients with coronary or cerebral atherosclerotic disease. Circulation (2000) 1 0 2 :7 28–735 .
  • ••First report of Phase II trial of lotrafiban, a new orally-activeGPIIb/IIIa antagonist. The study assessed the safety, tolerability, pharmacokinetics and effect on platelet aggregation of lotrafiban in a 12-week, double-blind, placebo-controlled, dose-ranging study in patients with recent MI, unstable angina, TIA, or stroke when added to aspirin therapy. The agent was well-tolerated. There was a dose-dependent relation with respect to inhibition of platelet aggregation.
  • GIUGLIANO RP, MCCABE CH, SEQUEIRA RF et al.: First report of an intravenous and oral glycoprotein I1b/Illa inhibitor (RPR 109891) in patients with recent acute coronary syndromes: Results of the TIMI15A and 15B trials. Am. Heart J. (2000) 140:81–93.
  • ••First trials of RPR 109891, a GPIIb/IIIa blocker effective bothintravenously and orally in acute coronary syndromes. Intravenous RPR 109891 is a potent, predictable, dose-related platelet inhibitor. Oral RPR 109891600mg/day) achieves moderate platelet inhibition.
  • THE SYMPHONY INVESTIGATORS: Comparison of sibrafiban with aspirin for prevention of cardiovas-cular events after acute coronary syndromes: a randomised trial. Sibrafiban versus Aspirin to Yield Maximum Protection from Ischemic Heart Events Post-acute Coronary Syndromes. Lancet (2000) 355:337–345.
  • ••A Phase III, multicentre, randomised trial of oral blockersibrafiban in patients with acute coronary syndromes. The 90-day rate of the primary end-point did not differ signifi-cantly between the groups assigned aspirin. The groups did not differ significantly in the rates of the component events or secondary efficacy end-points. Major bleeding was more common with high-dose sibrafiban than with aspirin or low-dose sibrafiban.
  • O'NEILL WW, SERRUYS P, KNUDTSON M et al.: long-term treatment with a platelet glycoprotein-receptor antagonist after percutaneous coronary revasculariza-tion. EXCITE Trial Investigators. Evaluation of Oral Xemilofiban in Controlling Thrombotic Events. N Engl. J. Med. (2000) 342:1316–1324.
  • •A multicentre, randomised, placebo-controlled Phase III trial of the oral platelet GPIIb/IIIa antagonist xemilofiban in patients undergoing PCI procedures. At 1 and 6 months, no significant differences existed among the treated and placebo groups in composite events. In patients undergoing PCI, xemilofiban did not significantly reduce the composite incidence of death, MI, or urgent revascularisation. There was a disturbing trend toward increased mortality in the lower dose xemilofiban group.
  • CANNON CP, MCCABE CH, WILCOX RG et al.: Oral glycoprotein I1b/Illa inhibition with orbofiban in patients with unstable coronary syndromes (OPUS-TIM1 16) trial. Circulation (2000) 102:149–156.
  • TOPOL EJ, EASTON JD, AMARENCO P et al: Design of the blockade of the glycoprotein I1b/Illa receptor to avoid vascular occlusion (BRAVO) trial. Am. Heart J. (2000) 139:927–933.
  • ••A report and design of the clinical trials for new GPIIb/IIIablocker lotrafiban in patients with recent MI, unstable angina, TIA, or ischaemic stroke, or who present at any time after a diagnosis of peripheral vascular disease combined with either cardiovascular or cerebrovascular disease. The agent was well-tolerated. There was a dose-dependent relation with respect to inhibition of platelet aggregation. On the basis of the results, a dosing regimen was selected for the Phase III trial (BRAVO), which is currently underway. The trial is broad in scope in terms of arterial beds and the patients are those who are at high risk of subsequent events and who may have the most potential for clinical benefit.
  • DEWOOD MA, SPORES J, NOTSKE R et al.: Prevalence oftotal coronary occlusion during the early hours of transmural myocardial infraction. N Engl. J. Med. (1980) 303:897–902.
  • MIZUNO K, SATOMURA K, MIYAMOTO A et al.: Angioscopic evaluation of coronary artery thrombi in acute coronary syndromes. N Engl. J. Med. (1992) 326:287–291.
  • FALK E, SHAH PK, FUSTER V: Coronary plaque disrup-tion. Circulation (1995) 92:657–671.
  • FUSTER VT, BADIMON J, CHESEBRO J: The pathogenesisof coronary artery disease and acute coronary syndromes. N Engl. J. Med (1992) 326:242–250.
  • TURITTO VT, BAUMGARTNER HR: Platelet-surfaceinteractions. In: Hem ostasis, and Thrombosis, Basic Princi-ples and Clinical Practice. Colman RW, Hirsh J, Marder VJ et al. (Eds.), JB Lippincott, Philadelphia, USA (1982):364–379.
  • CAPRIE STEERING COMMITTEE: A randomized, blinded, trial of Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE). Lancet (1996) 348:1329–1339.
  • ••A randomised trial of the thienopyridine, clopidogrel inreducing events of MI, stroke, or vascular death. Clopidogrel treatment was associated with a significant relative risk reduction of 8.7% compared with aspirin.
  • ANTIPLATELET THERAPY TRIALIST COLLABORATORS: Collaborative overview of randomized trials of antiplatelet therapy. I: prevention of death, myocar-dial infarction and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ (1994) 308:81–106.
  • ••Review of a huge amount of clinical trials of antiplatelettreatment with aspirin. Antiplatelet treatment is associated with a reduction of MI, stroke, or vascular death.
  • MARGUERIE GA, EDGINGTON TS, PLOW EF: Interactionof fibrinogen with its platelet receptor as part of a multistep reaction in ADP-induced platelet aggrega-tion. J. Biol. Chem. (1980) 255:154–61.
  • FROJMOVIC MM, O'TOOLE TE, PLOW EF et al: Plateletglycoprotein lib-IIIa (allb133 in tegr in) confers fibrino-gen - and activation-dependent aggregation on heterologous cells. Blood (1991) 78:369–376.
  • TOPOL EJ: Prevention of cardiovascular ischemiccomplications with new platelet glycoprotein IIb/IIIa inhibitors. Am. Heart J. (1995) 130:666–672.
  • SIMS PJ, GINSBERG MH, PLOW EF, SHATTIL SJ: Effect of platelet activation on the conformation of the plasma membrane glycoprotein lib-IIIa complex .j Biol. Chem. (1991) 266:7345–7352.
  • •Demonstration of the ligand-induced binding sites (LIBS) for monoclonal antibodies recognising neoepitopes.
  • D'SOUZA SE, GINSBERG MH, PLOW EF: Arginyl-glycyl- aspartic acid (RGD): a cell adhesion motif. Trends Biochem. ScL (1991) 16:246–250.
  • •A common binding site motif of several adhesion proteins for integrin receptors.
  • THE EPIC INVESTIGATORS: Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. N Engl. J. Med. (1994) 330:956–961.
  • ••First large trial of iv. GPIIb/IIIa antagonist in patients withacute coronary syndromes. Abciximab resulted in a 35% reduction of primary end point.
  • THE IMPACT II INVESTIGATORS: Effects of competitive platelet glycoprotein Hb/IIIa inhibition with integrelin in reducing complications of percutaneous coronary intervention. Lancet (1997) 349:1422–1428.
  • THE CAPTURE INVESTIGATORS: Randomized placebo-controlled trial of abciximab before and during intervention in refractory unstable angina: the CAPTURE Study. Lancet (1997) 349:1429–1435.
  • THE RESTORE INVESTIGATORS: Effects of platelet glycoprotein IIb/IIIa blockade with tirofiban on adverse cardiac events in patients with unstable angina or acute myocardial infarction undergoing coronary angioplasty. Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis. Circulation (1997) 96:1445–1453.
  • THE PRISM STUDY INVESTIGATORS: A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina. N Engl. J. Med. (1998) 338:1488–1505.
  • THE PRISM-PLUS STUDY INVESTIGATORS: Inhibition ofthe platelet glycoprotein Hb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocar-dial infarction. N Engl. J. Med. (1998) 338:1488–1497.
  • THE PARAGON INVESTIGATORS: A randomized trial ofpotent platelet IIb/IIIa antagonism, heparin or both in patients with unstable angina. Circulation (1996) 94:1-553. Abstract.
  • THE PURSUIT INVESTIGATORS: Inhibition of theplatelet glycoprotein Hb/IIIa with eptifibatide in patients with acute coronary syndromes without persistent ST-segment elevation. N Engl. J. Med. (1998) 339:436–443.
  • MERLINI PA, BAUER KA, OLTRONA L et al.: Persistentactivation of the coagulation system in unstable angina and myocardial infarction. Circulation. (1994) 90:61–68.
  • THE GUSTO-IIB INVESTIGATORS: A comparison ofrecombinant hirudin with heparin for the treatment of acute coronary syndromes. N. Engl. J. Med. (1996) 335:775–782.
  • COOK JJ, GLASS JD, SITKO GR et al.: Nonpeptide glycoproteinIlia inhibitors: 14: oral antithrom-botic efficacy of L-738,167 in a conscious canine model of coronary artery electrolytic injury. Circulation (1997) 96:949–958.
  • FEUEURSTEIN G, VASKO-MOSER J, KOSTER P: Effects ofSB 214857 on in vitroplatelet aggregation. Effects of SB 214857 on ex vivo platelet aggregation in dog and monkey. Investigator brochures, SmithKline Beecham.
  • FEUEURSTEIN G, VASKO-MOSER J, KOSTER P: Effects ofSB 214857 on platelet-dependent coronary thrombosis in the canine `folts model'. Effects of SB 214857 on dog coronary thrombosis in LCX wire. Investigator brochures, SmithKline Beecham.
  • SZALONY JA, HAAS NF, SALYERS AK et al.: Extendedinhibition of platelet aggregation with the orally active platelet inhibitor SC-54684A. Circulation (1995) 91:411–416.
  • MULLER TH, WEISENBERGER H, BRICKL R, NARJES H, HIMMELSBACH F, KRAUSE J: Profound and sustained inhibition of platelet aggregation by fradafiban, a nonpeptide platelet glycoproteinantagonistand its orally active prodrug, lefradafiban, in men. Circulation (1997) 96:1130–1138.
  • SAMANEN JM, ALT FA, BARTON LS, BONDINELL WE et al.: Potent, selective, orally active 3-oxo-1,4-benzo diazepine GPIlb Alla in tegrin antagonists. J. Med. Chem. (1996) 39:4867–4870.
  • ••Synthesis and structure-activity relationship of lotrafiban.
  • COLLER BS: Platelet GPIlb/Illa antagonists: The first anti-integrin receptor therapeutics. j Clin. Invest. (1997) 99:1467–1471.
  • WONG A, HWANG SM, JOHANSON K et al.: Binding of PHFSK&F 107260 and [31-1]-SB 214857 to purified integrin OCiam evidence for a common binding site for cyclic arginyl-glycinyl-aspartic acid peptides and nonpeptides. Pharmacol. Exp. Ther. (1998) 285: 228–235.
  • •Demonstration of a common mechanism of competitive antagonist at the fibrinogen binding site.
  • FEUERSTEIN G, WONG A, NICHOLS A et al: SB 214857: A novel non-peptide orally active potent and selective platelet GPIlb/Illa receptor antagonist: In vitro and in vivo pharmacology. Circulation (1996) 94 (Suppl. D:513.
  • HOEKSTRA WJ, POULTER BL: Combinatorial chemistry techniques applied to nonpeptide integrin antago-nists. Curr. Med. Chem. (1998) 5:195–204.
  • NICHOLSON NS, PANZER KNODLE SG et al.: Antiplatelet and antithrombotic effects of platelet glycoprotein 'lb/Ma (GPI1b/Illa) inhibition by arginine-glycine-asp artic acid-serine (RGDS) and arginine-glycine-aspar tic acid (RGD) (0-me)Y (SC-46749). J. Pharmacol. Exp. Ther. (1991) 256:876–882.
  • STEINER B, HARING P, JENNINGS LK, KOUNS WC: Five independent neo-epitopes on GPIlb-IIIa are differen-tially exposed by two potent peptidomimetic platelet inhibitors. Throm. Haemost. (1993) 69:Abstract 860.
  • ••Differential effect of different GPIIb/IIIa antagonists in LIBSexpression of possible clinical significance with respect to thrombocytopoenia occurrence.
  • KOUNS WC, KIRCHHOFER D, HADVARY P et al.: Reversible conformational changes induced in glycoprotein Hb/IIIa by a potent and selective peptidomimetic inhibitor. Blood (1992) 80:2539–2547.
  • VORCHHEIMER DA, FUSTER V: Oral platelet glycopro-tein Hb/IIIa receptor antagonists: The present challenge is safety. Circulation (1998) 97:312–314.
  • ••Review of some of the safety issues regarding this class ofdrugs.
  • MILLER WH, KU TW, ALT FE et al.: Enantiospecific synthesis of SB 214857, a potent, orally active non peptide fibrinogen receptor antagonist. Tetrahedron Lett. (1995) 36:9433–9436.
  • ••Structure-activity relationship and stereospecificity oflotrafiban.
  • ALT FE, BENNETT DB, CALVO RR et al.: Conformationally constrained peptides and semipeptides derived from RGD as potent inhibitors of the platelet fibrinogen receptor and platelet aggregation. J. Med. Chem. (1994) 37:769–780.
  • KU TVV, ALT FE, BARTON LS et al.: Direct design of a potent non-peptide fibrinogen receptor antagonist based on the structure and conformation of highly constrained cyclic RGD peptides. J. Am. Chem. Soc. (1993) 115:8861–8862.
  • SAMANEN J, ALT FE, BARTON L et al.: GPIlb/IIIa antago-nists with long oral duration designed from cyclic peptides. Proceedings 14th American Peptide Symposium. Mayflower Scientific, Kingswinford, UK (1995).
  • PLOW EF, GINSBERG MH: Cellular adhesion:GPM/lilaas a prototypic adhesion receptor. Prog. Hemost. Thromb. (1988) 9:117–156.
  • PYTELA R, PIERSCHBACHER MD, GINSBERG MH et al.:Platelet membrane glycoprotein 'lb/Ma: member of a family of arg-gly-asp-specific adhesion receptors. Science (1986) 231:1559–1562.
  • KLOCZEWIAK M, TIMMONS S, HAWIGER J et al: c a li z a -tion of a site interacting with human platelet receptor on carboxy-terminal segment of human fibrinogen. Biochem. Biophys. Res. Commun. (1982) 107:181–187.
  • FARRELL DH, THIAGARAJAN P, CHUNG DW, DAVIE EW:Role of fibrinogen alpha and gamma chain sites in platelet aggregation. Proc. Natl. Acad. Sci. USA (1992) 89:19729–10732.
  • DAVIS HM, HWANG SM, FREED SHETH MI: Comparisonof inhibition of platelet aggregation and GPIlb/Illa receptor occupancy: Evaluation of the effects of SB 214857, a low molecular weight (IMW) GPIlb /Mareceptor antagonist. Blood (1997) 90 (Suppl.) Pt 1:299A.
  • TSAO PW, FORSYTHE MS, MOUSA SA: Dissociationbetween the anti-aggregatory and anti-secretory effects of platelet in tegr in allb 13m (GPIlb/Illa) antago-nists, c7E3 and DMP728. Thromb. Res. (1997) 88:137–146.
  • CARROLL RC, WANG XF, LANZA F, STEINER B, KOUNSWC: Blocking platelet aggregation inhibits thromboxane A2 formation by low dose agonists but does not inhibit phosphorylation and activation of cytosolic phospholipase A2. Thromb. Res. (1997) 88:109–125.
  • FEUERSTEIN GZ: SB-214857-A potent and selectiveorally active GP lib/Ilia antagonist for treatment of thrombotic disorders. IBC. Int. Symp. Adv. Anticoag. Antithrombot. Thtobolyt. Ther. (1995) 6:23–25.
  • SEVENTH IBC INTERNATIONAL SYMPOSIUM: Advancesin Anticoagulant, Antithrombotic and Thrombolytic drugs. IDDB Meeting Report (1996) October 21–23.
  • VORCHHEIMER DA, GUZMAN IC, GREENBERG S et al:Safety and efficacy of eptifibatide therapy in patients with previous stroke or transient ischemic attack. J Am. Coll Cardiol (1999) 33 (Suppl.):330A.
  • SCARBOROUGH RM, KLEIMAN NS, PHILLIPS DR: Plateletglycoprotein ITh/IIIa antagonists - What are the relevant issues concerning their pharmacology and clinical use? Circulation (1999) 100:437–444.
  • ••Recent summary of clinical trials and safety issues regardingthis class of antiplatelet drugs.
  • SANE DC, DAMARAJU LV, TOPOL EJ: Occurrence and clinical significance of pseudothrombocytopenia during abciximab therapy. J. Am. Coll. Cardiol (2000) 36:75–83.
  • COLLER BS: Monitoring platelet GPIlb/Illa antagonisttherapy. Circulation (1997) 96:3828–3832.

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  • INVESTOR SERVICES - SMITHKLINE BEECHAM: SmithKline Beecham reports earnings per share increase of 15 per cent for first quarter 1999, 13 per cent excluding currency. Performance driven by increased volume from a broad product portfolio. www.sb.com/investor/qrs1999/1q99text.html (2000) .

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