Asunto(s)
Angioplastia Coronaria con Balón , Trombosis Coronaria/diagnóstico , Trombosis Coronaria/terapia , Anticoagulantes/uso terapéutico , Clopidogrel , Trombosis Coronaria/complicaciones , Procedimientos Quirúrgicos Electivos , Eptifibatida , Femenino , Heparina/uso terapéutico , Humanos , Persona de Mediana Edad , Péptidos/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ticlopidina/análogos & derivados , Ticlopidina/uso terapéuticoAsunto(s)
Enfermedad Coronaria/tratamiento farmacológico , Enfermedad Coronaria/cirugía , Inhibidores de Agregación Plaquetaria/uso terapéutico , Stents , Aspirina/uso terapéutico , Enfermedad Coronaria/economía , Quimioterapia Combinada , Humanos , Inhibidores de Agregación Plaquetaria/economía , Ticlopidina/uso terapéuticoRESUMEN
Coronary perforation is an uncommon but potentially life-threatening complication of percutaneous coronary intervention. The use of both atheroablative technologies for coronary intervention and adjunctive platelet glycoprotein blockade pharmacology may increase the incidence of or risk for life-threatening bleeding complications following the occurrence of coronary artery perforation. The interventional database for 6,214 percutaneous coronary interventions performed between January 1995 and June 1999 was analyzed. Hospital charts and cine angiograms for all patients identified in the database as having had coronary perforation were reviewed. Coronary perforation complicated 0.58% of all procedures and was more commonly observed in patients with a history of congestive heart failure and following use of atheroablative interventional technologies (2.8%). There was no association of abciximab therapy with either the incidence of or classification for coronary perforation. Adverse clinical outcomes (death, emergency surgical exploration) were related to the angiographic classification of perforation and were more frequently observed in patients who experienced a class 3 coronary perforation. These data suggest that specific clinical and procedural demographic factors are associated with the occurrence and severity of angiographic coronary perforation. An angiographic perforation class-specific algorithm for treatment of coronary perforation is proposed.
Asunto(s)
Algoritmos , Angioplastia Coronaria con Balón/instrumentación , Angioplastia por Láser/instrumentación , Anticuerpos Monoclonales/efectos adversos , Aterectomía Coronaria/instrumentación , Enfermedad Coronaria/terapia , Vasos Coronarios/lesiones , Lesiones Cardíacas/terapia , Hemorragia/inducido químicamente , Fragmentos Fab de Inmunoglobulinas/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Stents , Abciximab , Anciano , Anticuerpos Monoclonales/administración & dosificación , Cineangiografía , Angiografía Coronaria , Enfermedad Coronaria/diagnóstico por imagen , Femenino , Lesiones Cardíacas/diagnóstico por imagen , Hemorragia/diagnóstico por imagen , Hemorragia/terapia , Humanos , Fragmentos Fab de Inmunoglobulinas/administración & dosificación , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/administración & dosificación , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Placebo-controlled randomized trials of platelet glycoprotein (GP) IIb/IIIa blockade during percutaneous coronary intervention have demonstrated efficacy of these agents for reducing the risk of periprocedural ischemic events. However, cost-effectiveness of this adjunctive pharmacotherapy has been scrutinized. Extrapolation of cost-efficacy observations from clinical trials to "real world" interventional practice is problematic. METHODS: Consecutive percutaneous coronary interventions (n = 1472) performed by Ohio Heart Health Center operators at The Christ Hospital, Cincinnati, Ohio, in 1997 were analyzed for procedural and long-term (6-month) outcomes and charges. Observations on cost and efficacy (survival) were adjusted for nonrandomized abciximab allocation by means of "propensity scoring" methods. RESULTS: Abciximab therapy was associated with a survival advantage to 6 months after percutaneous coronary intervention. The average reduction in mortality rate at 6 months was 3.4% (unadjusted) and 4.9% when adjusted for nonrandomization. The average charge increment to 6 months was $1512 (unadjusted) and $950 when adjusted for nonrandomization. Patients deriving the greatest reduction in mortality rates also had a reduction in total cardiovascular charges to 6 months. Distinguishing demographics of this population included multivessel coronary intervention, coronary stent deployment, intervention within 1 week of myocardial infarction, and lower left ventricular ejection fraction. The average cost per life-year gained in this study was $2875 for all patients (unadjusted) and $1243 when adjusted for nonrandomization. CONCLUSIONS: Abciximab provides a cost-effective survival advantage in high-volume interventional practice that compares favorably with currently accepted standards. Clinical and procedural demographics associated with increased cost-effectiveness included multivessel coronary intervention, stent deployment, recent (<1 week) myocardial infarction, and impaired left ventricular function.
Asunto(s)
Angioplastia Coronaria con Balón/mortalidad , Anticuerpos Monoclonales/economía , Enfermedad Coronaria/economía , Fragmentos Fab de Inmunoglobulinas/economía , Inhibidores de Agregación Plaquetaria/economía , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Abciximab , Anticuerpos Monoclonales/uso terapéutico , Enfermedad Coronaria/mortalidad , Enfermedad Coronaria/terapia , Análisis Costo-Beneficio , Femenino , Humanos , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Masculino , Persona de Mediana Edad , Ohio/epidemiología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pronóstico , Tasa de Supervivencia/tendenciasRESUMEN
Platelet glycoprotein (GP) IIb/IIIa receptor blockade improves clinical outcomes after percutaneous coronary intervention (PCI) and for patients who present with non-ST-segment elevation acute coronary syndromes. Although this class of therapeutic agents has been defined by a common affinity for the platelet GP IIb/IIIa receptor, the 3 currently available agents differ markedly in pharmacodynamic and pharmacokinetic profile as well as receptor affinity. Differential (separate) binding sites on the GP IIb/IIIa receptor explain the observation that abciximab binding to platelets is not influenced by either tirofiban or eptifibatide. Abciximab (ReoPro, chimeric 7E3 Fab) is a low K(d) (high affinity) agent with a very short plasma t(1/2) and a prolonged duration of action at the platelet target receptor. Eptifibatide and tirofiban are high K(d) (low affinity) agents with a relatively long plasma t(1/2) and short duration of action at the platelet target receptor. These pharmacodynamic differences underlie the phenomena of gradual redistribution in abciximab binding and smooth tapering of abciximab antiplatelet effect after discontinuation of therapy. Furthermore, abciximab demonstrates affinity for both the CD11b/18 (alpha(m)beta(2) or MAC 1) and alpha(V)beta(3) (vitronectin) receptors. Although a survival advantage in favor of abciximab has been observed after PCI in both randomized controlled trials and high-volume clinical practice, no survival benefit has been observed to date after eptifibatide or tirofiban therapy for PCI. The mechanism of survival advantage after abciximab therapy has not been defined but may be distinct from the degree of platelet GP IIb/IIIa receptor inhibition during the duration of intravenous treatment. Although this important new "class" of therapeutic agent was simplistically defined by a common affinity for the GP IIb/IIIa receptor, this solitary unifying attribute may not define agent-specific benefit.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Abciximab , Anticuerpos Monoclonales/farmacología , Eptifibatida , Humanos , Fragmentos Fab de Inmunoglobulinas/farmacología , Péptidos/farmacología , Péptidos/uso terapéutico , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/farmacología , Ensayos Clínicos Controlados Aleatorios como Asunto , Tirofibán , Tirosina/análogos & derivados , Tirosina/farmacología , VitronectinaAsunto(s)
Angioplastia Coronaria con Balón , Infarto del Miocardio/terapia , Reperfusión Miocárdica , Terapia Trombolítica , Cateterismo Cardíaco , Humanos , Infarto del Miocardio/fisiopatología , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Pronóstico , Grado de Desobstrucción Vascular , Función Ventricular IzquierdaAsunto(s)
Angina de Pecho/tratamiento farmacológico , Infarto del Miocardio/complicaciones , Péptidos/administración & dosificación , Inhibidores de Agregación Plaquetaria/administración & dosificación , Adulto , Angina de Pecho/diagnóstico , Angina de Pecho/etiología , Angina de Pecho/terapia , Angioplastia Coronaria con Balón , Angiografía Coronaria , Electrocardiografía , Eptifibatida , Estudios de Seguimiento , Humanos , Infusiones Intravenosas , Masculino , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/terapia , Resultado del TratamientoRESUMEN
Adjunctive platelet glycoprotein IIb/IIIa blockade during percutaneous coronary intervention (PCI) reduces platelet-mediated adverse ischemic outcomes. Although abciximab, eptifibatide, and tirofiban have received U.S. Food and Drug Administration approval for use, these agents differ in their pharmacodynamic profiles. Each of these agents has been compared in randomized trials with placebo for patients undergoing PCI, but no randomized comparative studies of these agents have been performed. We compared ex vivo platelet function by both standard light transmission aggregometry and rapid platelet function assay during and after administration of abciximab, eptifibatide, or tirofiban in approved dose regimens on a randomized basis at the time of PCI in patients with unstable angina pectoris. A reduced intensity of platelet inhibition by light transmission aggregometry was observed for tirofiban compared with either eptifibatide or abciximab. In addition, the 30-minute bolus strategy used for tirofiban was associated with delayed onset of maximal platelet inhibition relative to the initiation of bolus infusion. Whether the trends in platelet function observed in this study will be translated into differences in clinical outcomes awaits definition by larger scale randomized clinical trials comparing these platelet glycoprotein IIb/IIIa inhibitors.
Asunto(s)
Angina Inestable/terapia , Angioplastia Coronaria con Balón , Anticuerpos Monoclonales/uso terapéutico , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Péptidos/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Tirosina/análogos & derivados , Abciximab , Angina Inestable/sangre , Anticuerpos Monoclonales/administración & dosificación , Plaquetas/efectos de los fármacos , Eptifibatida , Femenino , Estudios de Seguimiento , Humanos , Fragmentos Fab de Inmunoglobulinas/administración & dosificación , Inyecciones Intravenosas , Masculino , Péptidos/administración & dosificación , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Recuento de Plaquetas , Factores de Tiempo , Tirofibán , Resultado del Tratamiento , Tirosina/administración & dosificación , Tirosina/uso terapéuticoRESUMEN
BACKGROUND: Parenteral administration of platelet glycoprotein IIb/IIIa (GP IIb/IIIa) receptor blockers can reduce ischemic complications of coronary angioplasty. Orally active GP IIb/IIIa blockers may allow more sustained receptor antagonism with the potential for long-term secondary prevention. The pharmacodynamic efficacy, clinical safety, and outcomes after prolonged receptor blockade with an orally active GP IIb/IIIa antagonist are not known. The Oral Glycoprotein IIb/IIIa Receptor Blockade to Inhibit Thrombosis (ORBIT) Trial is a multicenter, placebo-controlled, randomized trial of xemilofiban, an oral platelet GP IIb/IIIa blocking agent, administered to patients after percutaneous coronary intervention. METHODS AND RESULTS: After successful elective percutaneous coronary intervention, 549 patients were randomized to receive either placebo or xemilofiban in a dose of 15 or 20 mg. Stented patients randomized to placebo also received ticlopidine 250 mg orally BID for 4 weeks. Patients who received abciximab during the coronary intervention and who were randomized to receive xemilofiban were administered a reduced dosage (10 mg TID for 2 weeks) followed by the randomized maintenance dose of 15 or 20 mg BID for 2 more weeks. All patients received 325 mg aspirin PO QD. Ex vivo platelet aggregation in response to 20 micromol/L ADP and 4 microg/mL collagen was measured over time after the initial dose of study drug and at days 14 and 28 of long-term therapy in 230 patients. All patients were followed clinically for 90 days. Xemilofiban inhibited platelet aggregation to both ADP and collagen with peak levels of inhibition that were similar at 14 and 28 days of long-term oral therapy. Plasma levels of xemilofiban correlated with the degree of platelet inhibition. Peak platelet inhibition on day 1 correlated with the subsequent occurrence of insignificant or mild bleeding events. Although this study was not powered to evaluate differences in clinical outcomes, a trend (P=0.04) was observed for reduction of cardiovascular events at 3 months in patients not treated with abciximab who received the highest dose (20 mg) of xemilofiban studied. CONCLUSIONS: Xemilofiban inhibited platelet aggregation and was well tolerated during 28 days of long-term oral therapy. The observed trend in reduction of cardiovascular events in follow-up awaits confirmation in the larger-scale phase III study (EXCITE trial) currently in progress.
Asunto(s)
Benzamidinas/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Benzamidinas/efectos adversos , Benzamidinas/farmacocinética , Transfusión Sanguínea , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Agregación Plaquetaria/efectos de los fármacos , Resultado del TratamientoRESUMEN
BACKGROUND: Inhibition of platelet aggregation with parenteral glycoprotein (GP) IIb/IIIa receptor blockers can reduce the ischemic complications of angioplasty. Sustained efficacy and safety of protracted GP IIb/IIIa blockade with an orally administered agent have not previously been determined. This study is the first randomized, dose-ranging, single-blind, placebo-controlled trial of xemilofiban, an oral platelet GP IIb/IIIa receptor antagonist, administered to patients after intracoronary stent deployment. The pharmacodynamic efficacy of xemilofiban-induced platelet inhibition and clinical safety of this agent was evaluated during chronic therapy. METHODS AND RESULTS: After elective intracoronary stent deployment, patients were randomized to receive placebo (250 mg ticlopidine P.O. BID) or xemilofiban in doses of 5, 10, 15, or 20 mg P.O. BID. All patients received 325 mg aspirin P.O. QD. Inhibition of ex vivo platelet aggregation in response to 20 micromol/L ADP and 4 microg/mL collagen was measured over time after the initial dose of study drug and at 1 and 2 weeks of chronic therapy. Study drug was discontinued after 2 weeks, and all patients were followed clinically for > or = 30 days. Oral xemilofiban resulted in a dose-dependent inhibition of platelet aggregation in response to both agonists that was sustained through 2 weeks of chronic therapy. Doses of xemilofiban required to achieve > or = 50% inhibition of platelet aggregation were > or = 10 mg, and the duration of inhibition was 8 to 10 hours. No significant hemorrhagic episodes or blood transfusions were observed in this trial. CONCLUSIONS: Oral xemilofiban in doses of > or = 10 mg produced > or = 50% inhibition of platelet aggregation in response to ADP and collagen for 8 to 10 hours after dosing. Platelet inhibition was sustained through 2 weeks of chronic therapy. The optimal duration of oral GP IIb/IIIa blockade to effectively suppress recurrent ischemic events after coronary intervention remains to be determined.
Asunto(s)
Benzamidinas , Inhibidores de Agregación Plaquetaria/uso terapéutico , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Stents , Abciximab , Administración Oral , Anciano , Anticuerpos Monoclonales/uso terapéutico , Aspirina/uso terapéutico , Enfermedad Coronaria/terapia , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Masculino , Persona de Mediana Edad , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Método Simple Ciego , Trombosis , Ticlopidina/uso terapéuticoRESUMEN
First-time abciximab administration was associated with acute profound thrombocytopenia in 4 of 575 consecutive patients. Therapy with platelet transfusion, but not intravenous immunoglobulin, was associated with a rapid and sustained increment in circulating platelet count and clinical hemostasis.
Asunto(s)
Anticuerpos Monoclonales/efectos adversos , Fragmentos Fab de Inmunoglobulinas/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Trombocitopenia/etiología , Abciximab , Adulto , Femenino , Humanos , Inmunoglobulina G/administración & dosificación , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Transfusión de Plaquetas , Trombocitopenia/terapiaRESUMEN
BACKGROUND: Placebo-controlled randomized trials of parenteral platelet glycoprotein (GP) IIb/IIIa receptor antagonists have demonstrated reduced ischemic complications of coronary angioplasty. Orally active GP IIb/IIIa blockers are being developed to allow more sustained receptor antagonism with potential for long-term secondary prevention. Sequential therapy with abciximab followed by an oral IIb/IIIa antagonist has not previously been reported. The clinical safety and pharmacodynamics of a sequential therapeutic strategy are unknown. METHODS AND RESULTS: Of 74 consecutive patients enrolled in a placebo-controlled, dose-ranging pharmacokinetic/pharmacodynamic study of xemilofiban, a new oral nonpeptide GP IIb/IIIa antagonist, after elective intracoronary stent placement, 17 patients received abciximab during stent deployment as a weight-adjusted intravenous bolus and 12-hour infusion at the discretion of the investigator. Ex vivo platelet aggregation in response to 20 mumol/L ADP and 4 micrograms/mL collagen was measured over time after the first dose of either xemilofiban (5, 10, 15, or 20 mg) or placebo (ticlopidine) administered 8 to 18 hours after termination of abciximab and again after 1 week of twice-daily oral administration of study drug. At baseline, patients who had received abciximab had lower platelet aggregation in response to both agonists (P < .001). A significant dose-response relationship to xemilofiban was observed. Patients who had received abciximab had lower ADP-induced (P < or = .010) and collagen-induced (P < or = .029) platelet aggregation after xemilofiban. This pharmacodynamic interaction was no longer evident at 1 week. No significant clinical bleeding events or blood product transfusions were observed in this trial. CONCLUSIONS: Both the magnitude and the duration of pharmacodynamic response to xemilofiban were enhanced by prior abciximab treatment. The potentiated pharmacodynamic response was not evident after 1 week. This observation has implications for the safety and efficacy of sequential parenteral-oral GP IIb/IIIa blockade therapy and may be useful in deriving dose regimens for orally administered compounds.
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Benzamidinas , Enfermedad Coronaria/tratamiento farmacológico , Fragmentos Fab de Inmunoglobulinas/administración & dosificación , Inhibidores de Agregación Plaquetaria/administración & dosificación , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Abciximab , Administración Oral , Adulto , Anciano , Enfermedad Coronaria/sangre , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Agregación Plaquetaria/efectos de los fármacosRESUMEN
STUDY OBJECTIVE: To evaluate a comprehensive diagnostic 9-hour evaluation (Heart ER Program) for patients with possible acute ischemic coronary syndromes. DESIGN: Retrospective review of consecutive patients. SETTING: Urban tertiary care emergency department. PARTICIPANTS: A total of 1,010 patients with symptoms suggestive of acute ischemic coronary syndrome was enrolled in the Heart ER Program over the first 32 months of operation. Patients with history of coronary artery disease, hemodynamic instability, acute ST-segment elevation or depression of more than 1 mm, or a clinical syndrome consistent with unstable angina were directly admitted to the hospital. INTERVENTION: Patients underwent serial testing for creatine kinase (CK-MB) on presentation to the Heart ER and 3, 6, and 9 hours later with continuous 12-lead ECGs/serial ST-segment trend monitoring for 9 hours. Two-dimensional echocardiography and graded exercise testing were performed in the ED after the 9-hour evaluation period. RESULTS: Of 1,010 patients, 829 (82.1%) were released home from the ED; 153 (15.1%) required admission for further cardiac evaluation. Fifty-two of 153 (33.9%) admitted patients were found to have a cardiac cause for their symptoms; 43 had acute ischemic coronary syndromes (12, acute myocardial infarction; 31, angina or unstable angina). CONCLUSION: The Heart ER program provides an effective method for evaluating low- to moderate-risk patients with possible acute ischemic coronary syndrome in the ED setting.